Internet Mental Health

BIPOLAR I DISORDER


WARNING:



President Trump is about to start a nuclear war with North Korea. New UN sanctions have cut North Korea's oil and money supply - hence its regime would soon fall without war. Both China and Russia have promised to defend North Korea if America attacks first. So America attacking North Korea could start a nuclear WW III. Nevertheless, President Trump will likely attack North Korea as a distraction from his possible impeachment.

Nuclear Strategists Call to Scrap ICBM Arsenal Before ICBMs Accidentally Start WWIII

By 2020 Climate Change Will Be Irreversible

By 2030 60% Of Tropical Rainforest Will Be Destroyed

Climate Change This Century Will Destroy India and Pakistan

Why Is This Warning On A Mental Health Website?

No such warning has ever been published on this website since its creation in 1995. However, the very high probability of a nuclear WW III, and the certainty of irreversible climate change in the next few years requires that this warning be posted. If Trump starts WW III, or does nothing to stop climate change, mental illness will be the least of our worries.





Expanded Quality of Life Scale For Bipolar I Disorder

Internet Mental Health Quality of Life Scale

Big 5 Factors Of Mental Illness And Code For This Disorder
(The "6th Big Factor" of Mental Health, "Physical Health", Is Coded Abnormal or Red)

  • Had at least 1 week of a manic episode which caused significant distress or disability

  • May have had a major depressive or hypomanic episode before or after this manic episode (but this is not required for the diagnosis)

  • This was not due to a medical or substance use disorder

Prediction

    Episodic for lifetime (average untreated manic episode lasts 4 months, average untreated depressive episode lasts 6 months)

Problems

Occupational-Economic Problems:

  • Causes significant impairment in academic, occupational and/or social functioning

  • Bipolar disorder accounts for 7% of the disability caused by mental illness worldwide

  • Only a minority are so chronically disabled that they require a disability pension

Impulsive, Disorderly (Disinhibition):

  • During manic phase (of abnormally elated or irritable mood) for at least 1 week, nearly every day, had the majority of the following:
    • Elated self-esteem or grandiosity

    • Decreased need for sleep

    • More talkative than usual

    • Flight of ideas or racing thoughts

    • Distractibility

    • Increase in goal-directed activity or psychomotor agitation

    • Reckless over-involvement

  • Manic episodes can cause irresponsibility and physical violence

Cognitive Impairment:

  • Depression and mania impair judgment; severe episodes can cause psychosis

Distressed, Easily Upset (Negative Emotion):

  • During depressive phase (of depressed mood or loss of interest or pleasure), nearly every day for at least 2 weeks had the majority of the following:
    • Depressed mood most of the day

    • Markedly diminished interest or pleasure

    • Significant weight loss when not dieting or weight gain

    • Insomnia or hypersomnia

    • Psychomotor agitation or slowing

    • Fatigue or loss of energy

    • Feelings of worthlessness or excessive guilt

    • Diminished ability to think or concentrate, or indecisiveness

    • Recurrent thoughts of death or suicide (or a suicide attempt)

  • Mixed episodes rapidly alternate between depressive and manic episodes in the same day/week

Medical:

  • Manic episodes cause: denial of illness, increased risk of death due to accident or other illness



Explanation Of Terms And Symbols

Internet Mental Health Quality of Life Scale

Note: The clinical features of Bipolar I Disorder, Depressive Episode, are identical to that of Major Depressive Disorder.


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Click Here For Free Diagnosis

Limitations of Self-Diagnosis

Self-diagnosis of this disorder is often inaccurate. Accurate diagnosis of this disorder requires assessment by a qualified practitioner trained in psychiatric diagnosis and evidence-based treatment.

However, if no such professional is available, our free computerized diagnosis is usually accurate when completed by an informant who knows the patient well. Computerized diagnosis is less accurate when done by patients (because they often lack insight).

Example Of Our Computer Generated Diagnostic Assessment

Bipolar I Disorder 296.4X, Most Recent Episode Manic

This diagnosis is based on the following findings:

  • Never had psychotic symptoms in the absence of prominent mood disturbances (when off drugs)

  • Manic episode is not better accounted for by Schizoaffective Disorder

  • Manic episode is not superimposed on Schizophrenia or Schizophreniform Disorder

  • Manic episode is not superimposed on Delusional Disorder or Psychotic Disorder Not Otherwise Specified

  • Manic episode was not due to a general medical condition

  • Manic episode was not due to a drug of abuse, a medication, or other treatment

  • Manic episode caused clinically significant distress or disability for at least 1 week

  • Manic episode had abnormally abnormally elevated or expansive mood for at least 1 week (still present)

  • Manic episode had inflated self-esteem or grandiosity for at least 1 week (still present)

  • Manic episode had decreased need for sleep for at least 1 week (still present)

  • Manic episode had unusual talkativeness or pressure to keep talking for at least 1 week (still present)

  • Manic episode had flight of ideas or racing thoughts for at least 1 week (still present)

  • Manic episode had distractibility for at least 1 week (still present)

  • Manic episode had increased goal-directed activity or agitation for at least 1 week (still present)

  • Manic episode had excessive involvement in reckless pleasurable activities for at least 1 week (still present)

  • Manic episode lacked psychotic features (when off drugs)

  • Had a previous Manic Episode, Mixed Episode, or Depressive Episode

Treatment Goals:

  • Goal: prevent abnormally elated mood.
    If this problem worsened: Her elevated, unusually good, cheerful, or high mood could lead to unceasing and indiscriminate enthusiasm for interpersonal, sexual, or occupational interactions.

  • Goal: prevent inflated self-esteem or grandiosity.
    If this problem worsened: Her uncritical self-confidence could lead to marked grandiosity. Despite lack of any particular experience or talent, she could embark on writing a novel or seek publicity for some impractical invention or cause. This could develop into grandiose delusions (e.g., having a special relationship to God to some public figure from the political, religious, or entertainment world).

  • Goal: prevent decreased need for sleep.
    If this problem worsened: She could awaken several hours earlier than usual, feeling full of energy. This could progress to going days without sleep and yet not feeling tired.

  • Goal: prevent unusual talkativeness or a pressure to keep talking.
    If this problem worsened: She could have pressured, loud, rapid, and difficult to interrupt speech. This could progress to talking nonstop, sometimes for hours on end, and without regard for others' wishes to communicate. She could become theatrical, with dramatic mannerisms and singing. If her mood was more irritable than expansive, her speech could be marked by complaints, hostile comments, or angry tirades.

  • Goal: prevent flight of ideas or racing thoughts.
    If this problem worsened: Her thoughts could race, often at a rate faster than she could articulate. This could progress to a flight of ideas in which there is a nearly continuous flow of accelerated speech, with abrupt changes from one topic to another. When flight of ideas is severe, speech could become disorganized and incoherent.

  • Goal: prevent distractibility.
    If this problem worsened: She could be unable to screen out irrelevant external stimuli. This could progress to having difficulty differentiating between thoughts that are germane to the topic and thoughts that are only slighly relevant or clearly irrelevant.

  • Goal: prevent abnormally increased goal-directed activity or agitation.
    If this problem worsened: She could have excessive planning of, and excessive participation in, multiple activities (e.g., sexual, occupational, political, or religious). This could involve increased sex drive, fantasies, and sexual behavior. This could progress to increased sociability (e.g., renewing old acquaintances or calling friends or even strangers at all hours of the day or night), without regard to the intrusive, domineering, and demanding nature of these interactions. This could further progress to psychomotor agitation or restlessness (e.g., pacing or holding multiple telephone conversations simultaneously).

  • Goal: prevent excessive involvement in reckless pleasurable activities.
    If this problem worsened: She could have imprudent involvement in pleasurable activities such as buying sprees, reckless driving, foolish business investments, and sexual behavior unusual for her. These activities could have painful consequences. Her unusually increased sexual behavior could include infidelity or indiscriminate sexual encounters with strangers.


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Bipolar Affective Disorder F31 - ICD10 Description, World Health Organization

A disorder characterized by two or more episodes in which the patient's mood and activity levels are significantly disturbed, this disturbance consisting on some occasions of an elevation of mood and increased energy and activity (hypomania or mania) and on others of a lowering of mood and decreased energy and activity (depression). Repeated episodes of hypomania or mania only are classified as bipolar.

    F31.0 Bipolar affective disorder, current episode hypomanic

    The patient is currently hypomanic, and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.

    F31.1 Bipolar affective disorder, current episode manic without psychotic symptoms

    The patient is currently manic, without psychotic symptoms (as in F30.1), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.

    F31.2 Bipolar affective disorder, current episode manic with psychotic symptoms

    The patient is currently manic, with psychotic symptoms (as in F30.2), and has had at least one other affective episode (hypomanic, manic, depressive, or mixed) in the past.

    F31.3 Bipolar affective disorder, current episode mild or moderate depression

    The patient is currently depressed, as in a depressive episode of either mild or moderate severity (F32.0 or F32.1), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past.

    F31.4 Bipolar affective disorder, current episode severe depression without psychotic symptoms

    The patient is currently depressed, as in severe depressive episode without psychotic symptoms (F32.2), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past.

    F31.5 Bipolar affective disorder, current episode severe depression with psychotic symptoms

    The patient is currently depressed, as in severe depressive episode with psychotic symptoms (F32.3), and has had at least one authenticated hypomanic, manic, or mixed affective episode in the past.

    F31.6 Bipolar affective disorder, current episode mixed

    The patient has had at least one authenticated hypomanic, manic, depressive, or mixed affective episode in the past, and currently exhibits either a mixture or a rapid alteration of manic and depressive symptoms. Excl.:single mixed affective episode (F38.0)

    F31.7 Bipolar affective disorder, currently in remission

    The patient has had at least one authenticated hypomanic, manic, or mixed affective episode in the past, and at least one other affective episode (hypomanic, manic, depressive, or mixed) in addition, but is not currently suffering from any significant mood disturbance, and has not done so for several months. Periods of remission during prophylactic treatment should be coded here.

Bipolar I Disorder, Manic Episode - Diagnostic Criteria, American Psychiatric Association


An individual diagnosed with bipolar I disorder needs to meet all of the following criteria:

  • For a diagnosis of bipolar I disorder, it is necessary to meet the following criteria for a manic episode. The manic episode may have been preceded by and may be followed by hypomanic or major depressive episodes.

    Manic Episode

    • A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently goal-directed behavior or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

    • During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms have persisted (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

      • Inflated self-esteem or grandiosity.

      • Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

      • More talkative than usual or pressure to keep talking.

      • Flight of ideas or subjective experience that thoughts are racing.

      • Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

      • Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., purposeless non-goal-directed activity).

      • Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

    • The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

    • The episode is not attributable to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or another medical condition.

      A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a manic episode and therefore a bipolar I diagnosis.

  • The above criteria constitute a manic episode. At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.

  • The occurrence of the manic and major depressive episode(s) is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

Bipolar I Disorder, Depressive Episode - Diagnostic Criteria, American Psychiatric Association


An individual diagnosed with bipolar I disorder, depressive episode, needs to meet all of the following criteria:

  • For a diagnosis of bipolar I disorder, it is necessary to have met the following criteria for a manic episode in the past.

    Manic Episode

    • A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently goal-directed behavior or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

    • During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms have persisted (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

      • Inflated self-esteem or grandiosity.

      • Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

      • More talkative than usual or pressure to keep talking.

      • Flight of ideas or subjective experience that thoughts are racing.

      • Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

      • Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., purposeless non-goal-directed activity).

      • Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

    • The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

    • The episode is not attributable to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or another medical condition.

      A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a manic episode and therefore a bipolar I diagnosis.

  • The above criteria constitute a manic episode. At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.

  • For a diagnosis of bipolar I disorder, depressive episode, it is necessary to currently meet the following criteria for a major depressive episode.

    Major Depressive Episode

    • Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

      Note: Do not include symptoms that are clearly attibutable to another medical condition.

      • Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)

      • Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

      • Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)

      • Insomnia or hypersomnia nearly every day.

      • Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).

      • Fatigue or loss of energy nearly every day.

      • Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

      • Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

      • Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

    • The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

    • The episode is not attributable to the physiological effects of a substance or to another medical condition.

      Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in the above criteria, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual's history and the cultural norms for the expression of distress in the context of loss.

    • The occurrence of the manic and major depressive episode(s) is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.


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Diagnostic Features

Bipolar I Disorder has a good outcome when treated but, if untreated, is one of the most severe forms of mental illness, and has a 15% risk of completed suicide. Bipolar I Disorder has a high rate of recurrence if untreated.

Bipolar I Disorder is a condition characterized by one or more Manic Episodes. These Manic Episodes may have been preceded by and may be followed by Hypomanic or Major Depressive Episodes. These Manic Episodes are not due to a medical condition, medication, abused substance, or a psychotic disorder.

    The Manic Episode must have abnormally and persistently elevated, expansive, or irritable mood plus abnormally and persistently increased goal-directed behavior or energy, which is present most of the day, nearly every day lasting for at least 1 week (or any duration if hospitalization is necessary). During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms (or four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior: (1) inflated self-esteem/grandiosity, (2) decreased need for sleep (e.g., feels rested after only 3 hours of sleep), (3) more talkative than usual, (4) flight of ideas/racing thoughts, (5) distractibility, (6) increase in goal-directed activity, (7) reckless over-involvement (e.g., buying sprees, sexual indiscretions, foolish business investments). The Manic Episode must cause marked impairment in social or occupational functioning or necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

In adults, mania is usually episodic with an elevation of mood and increased energy and activity. In children, mania is commonly chronic rather than episodic, and usually presents in mixed states with irritability, anxiety and depression. In adults and children, during depression there is lowering of mood and decreased energy and activity.

During a Mixed Episode there is a rapidly alternating mixture of manic and depressive symptoms. During the manic phase of a mixed episode, there may be moments, hours, or, more rarely, days of depressive symptoms.

    Warning: Self-diagnosis of this disorder is often inaccurate. Accurate diagnosis of this disorder requires assessment by a qualified practitioner trained in psychiatric diagnosis and evidence-based treatment. However, if no such professional is available, our free computerized diagnosis is usually accurate when completed by an informant who knows the patient well. Computerized diagnosis is less accurate when done by patients (because they often lack of insight).

Course

The first episode may occur at any age from childhood to old age. The average age at onset is 18 for both men and women. More than 90% of individuals who have a single Manic Episode go on to have future episodes. Untreated patients with Bipolar I Disorder typically have 8 to 10 episodes of mania or depression in their lifetime. Often 5 years or more may elapse between the first and second episode, but thereafter the episodes become more frequent and more severe. There is significant symptom reduction between episodes, but 25% continue to display mood instability or mild depression. As many as 30% show severe impairment in occupational functioning between acute episodes. Bipolar I Disorder may develop psychotic symptoms. The psychotic symptoms in Bipolar I Disorder only occur during severe manic, mixed or depressive episodes. In contrast, the psychotic symptoms in Schizophrenia can occur when there is no mania or depression. Poor recovery is more common after psychosis. Manic episodes usually begin abruptly and last for approximately 6 weeks. Depressive episodes last for approximately 11 weeks, and rarely for more than a year, except in the elderly.

Outcome of Schizophrenia

Mood Disorder Recovery At 10-Year Follow-up Compared To Schizophrenia

Complications

At 5-year follow-up, 90% of individuals who had a single manic episode had a recurrence; more than half were rehospitalized; only 40% had a good overall outcome; and 4% were dead. Manic episodes often result in school failure, occupational failure, divorce, child abuse, gambling, excessive debt, violence, or other episodic antisocial behavior. Psychosis in Bipolar I Disorder never occurs when mood is normal (unlike schizophrenia). Completed suicide occurs in 10-15% of individuals with Bipolar I Disorder, and account for one-quarter of all completed suicides. Suicidal ideation and attempts are more likely to occur when the individual is in a depressed or mixed state. Child abuse, spouse abuse, or other violent behavior may occur during severe Manic Episodes or during those with psychotic features. Individuals with Bipolar I Disorder have cognitive impairments which may contribute to impaired occupational and social functioning. These cognitive impairments often are lifelong, even when not having manic or depressive episodes.

Comorbidity

Comorbidity is the rule, not the exception, in Bipolar Disorder. The most frequent disorders that co-occur with Bipolar Disorder are Anxiety Disorders (in 75%) and Alcohol Use Disorder (50%). Other disorders that co-occur are substance use, ADHD, and disruptive, impulse-control, or conduct disorder. Metabolic syndrome and migraine are more common among individuals with Bipolar Disorder than in the general population.

Differential Diagnosis

Bipolar I Disorder must be distinguished from:

  • Mood Disorder Due to a General Medical Condition (e.g., due to multiple sclerosis, stroke, hypothyroidism, or brain tumor)

  • Substance-Induced Mood Disorder (e.g., due to drug abuse, antidepressant medication, or electroconvulsive therapy)

  • Other Mood Disorders (e.g., Major Depressive Disorder; Dysthymia; Bipolar II Disorder; Cyclothymic Disorder)

  • Psychotic Disorders (e.g., Schizoaffective Disorder, Schizophrenia, or Delusional Disorder)

  • Since this disorder may be associated with hyperactivity, recklessness, impulsivity, and antisocial behavior; the diagnosis of Bipolar I Disorder must be carefully differentiated from Attention Deficit Hyperactivity Disorder, Conduct Disorder, Antisocial Personality Disorder, and Borderline Personality Disorder

Associated Laboratory Findings

There are no diagnostic laboratory tests for Bipolar I Disorder. Thus diagnosis is arrived at by using standardized diagnostic criteria to rate the patient's behavior. Onset of mania after age 40 could signify that the mania may be due to a general medical condition or substance use. Current or past hypothyroidism (or even mild thyroid hypofunction) may be associated with Rapid Cycling. Hyperthyroidism may precipitate or worsen mania in individuals with a preexisting Mood Disorder. However, hyperthyroidism in individuals without preexisting Mood Disorder does not typically cause manic symptoms.

Prevalence

Bipolar I Disorder affects both sexes equally in all age groups and its lifetime prevalence in community samples varies from 0.4% to 1.6%. The U.S. 12-month prevalence is 0.6%. It can even present in preschoolers. There are no significant differences among racial groups in the prevalence of this disorder. Manic episodes tend to predominate in men; whereas depressive episodes tend to predominate in women.

Causation

In Bipolar I Disorder family, twin and adoption studies suggest genetic factors. The concordance rate for monozygotic (identical) twins is 43%; whereas it is only 6% for dizygotic (nonidentical) twins. About half of all patients with Bipolar I Disorder have one parent who also has a mood disorder, usually Major Depressive Disorder. If one parent has Bipolar I Disorder, the child will have a 25% chance of developing a mood disorder (about half of these will have Bipolar I or II Disorder, while the other half will have Major Depressive Disorder). If both parents have Bipolar I Disorder, the child has a 50%-75% chance of developing a mood disorder. First-degree biological relatives of individuals with Bipolar I Disorder have elevated rates of Bipolar I Disorder (4%-24%), Bipolar II Disorder (1%-5%), and Major Depressive Disorder (4%-24%).

The finding that the concordance rate for monozygotic twins isn't 100% suggests that environmental or psychological factors likely play a role in causation. Certain environmental factors (e.g., antidepressant medication, antipsychotic medication, electroconvulsive therapy, stimulants) or certain illnesses (e.g., multiple sclerosis, brain tumor, hyperthyroidism) can trigger mania. Mania can be triggered by giving birth, sleep deprivation, and major stressful life events.

Controlled Clinical Trials Of Therapy

Click here for a list of all the controlled clinical trials of therapy for this disorder.

Effective Therapies

The most important first step in the treatment of this disorder is to prevent alcohol or illicit drug abuse. Medication is highly effective in the treatment of Bipolar I Disorder. However, medication often is ineffective when the individual is still abusing alcohol or illicit drugs. Untreated patients often must be hospitalized to assure their safety and that of others.

FDA-Approved Drugs for Bipolar Type I Disorder

Drug Mania Depression Maintenance
Aripiprazole x
Asenapine x
Carbamazepine ER x
Cariprazine x
Chlorpromazine x
Lamotrigine x
Lithium x x
Loxapine (inhaled) x
Lurasidone x
Olanzapine x x
Olanzapine-fluoxetine combination x
Quetiapine x x
Risperidone x
Valproate, Divalproex ER x
Ziprasidone x x

FDA Approved Drug Products to treat Bipolar Disorder

Most patients respond to a combination of a mood stabilizer (lithium, valproate/divalproex, or carbamazepine) plus an antipsychotic medication. Clonazepam is added to treat mania. Antidepressant medication is often ineffective during depression, and must be stopped during mania (or it will increase the mania). Clozapine and electroconvulsive therapy (ECT) are used for treatment refractory patients. Psychological treatments are not a substitute for medication, but are helpful for depression (but not mania). Educating patients and their families about this disorder is always beneficial. Usually treatment results in a dramatic decrease in suffering, and causes an 8-fold reduction in suicide risk.

In mania, an antipsychotic medication and/or a benzodiazepine medication is often added to the mood-stabilizer.

There are only 3 FDA-approved treatments for bipolar depression (quetiapine, olanzapine-fluoxetine combination, and lurasidone). Although not yet FDA-approved for the treatment of bipolar depression, research on treatment with carbamazepine and valproate is encouraging; however treatment with lithium requires further testing. In bipolar depression, treatment non-responders, often respond to a combination of lithium and lamotrigine, or antidepressants in combination with either lithium, an antiepileptic drug or atypical antipsychotics. Alternatively, in depression, the mood-stabilizer can be switched to another mood-stabilizer, or two mood-stabilizers can be used together. Since antidepressant medication can trigger mania, antidepressant medication should always be combined with a mood-stablizer or antipsychotic medication to prevent mania.

Bipolar disorder usually becomes a lifelong, episodic disorder if an individual has two or more bipolar episodes. Thus it is essential to prevent future bipolar episodes by taking lifelong maintenance therapy with medication. Currently there are only 7 FDA-approved treatments for maintenance treatment of bipolar disorder: 2 mood-stabilizers (lithium, lamotrigine) and 5 antipsychotic medications (quetiapine, olanzapine, risperidone Consta, aripiprazole, ziprasidone) [usually used in combination with lithium or valproate].

Overall, research has shown that the most effective treatment for bipolar disorder is a combination of supportive psychotherapy, psychoeducation, and the use of a mood-stabilizer (often combined with an antipsychotic medication). There is no research showing that any form of psychotherapy is an effective substitute for medication.

Since a Manic Episode can quickly escalate and destroy a patient's career or reputation, a therapist must be prepared to hospitalize out-of-control manic patients before they "lose everything". Likewise, severely depressed, suicidal bipolar patients often require hospitalization to save their lives.

Although the medication therapy for Bipolar I Disorder usually must be lifelong, the majority of bipolar patients are noncompliant and stop their medication after one year. At 4-year follow-up of bipolar patients, 41% have a good overall outcome and 4% have died. Women with bipolar disorder lose, on average, 9 years in life expectancy, 14 years of lost productivity and 12 years of normal health

Best Recoveries

The best recoveries are achieved when individuals with Bipolar I Disorder:
  1. Get the correct diagnosis (since many are misdiagnosed as having schizophrenia or "just borderline personality")

  2. Get effective treatment and faithfully stay on it for a lifetime (most individuals require the combination of a mood-stabilizer plus an antipsychotic medication)

  3. Adopt a healthy lifestyle (regular sleep and exercise; no alcohol or drug abuse; low stress)

  4. Regularly see a supportive physician who is knowledgeable about the psychiatric management of this disorder

  5. Learn which symptoms predict the return of this illness, and what additional "rescue" medication should be taken

  6. Learn to trust the warnings given by family and friends when they see early signs of relapse

  7. Learn as much as possible about this illness from therapists, the Internet, books, or self-help groups

Ineffective Therapies

Cognitive behavioral therapy (CBT) is not effective in preventing relapse in bipolar I disorder; however CBT is effective in reducing symptoms in major depressive episodes, although the effect size is small. Vitamins, dietary supplements, and acupuncture are all ineffective for mood disorders.

A Dangerous Cult


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Lack Of Social Skills During Bipolar I Disorder

There are social skills that are essential for healthy social functioning. During depressive episodes of bipolar I disorder, individuals lack the essential social skills of self-confidence, optimism, belonging, and sociability. These are the same social skills that are lacking in individuals with major depressive disorder, persistent depressive disorder, avoidant personality disorder and social anxiety disorder.

    Social Skills That Are Lacking During The Depressed Episodes Of Bipolar I Disorder

    SOCIAL SKILL BIPOLAR DEPRESSION NORMAL
    Self-Confidence Feeling inferior or shy Having a good opinion of one's self and abilities; socially confident and out-going
    Optimism Pessimism or expecting the worst Having a positive outlook on life; expecting a good outcome; hopeful
    Belonging Fearing rejection by others Feeling liked and accepted by friends, and included in their group; not fearing rejection
    Sociability Social withdrawal Friendly; interested in social contacts and activities

During manic episodes of bipolar I disorder, individuals have all these social skills to excess. During mixed episodes of bipolar I disorder, individuals can rapidly alternate between manic and depressive episodes. Some believe that "negative thinking causes depression". This belief can't explain how bipolar individuals in a mixed phase can repeatedly alternate between depression and mania. This sudden switching strongly suggests that mixed bipolar I disorder has a physiological, rather than a psychological, causation.

Which Behavioral Dimensions Are Involved?

Research has shown that there are 5 major dimensions (the "Big 5 Factors") of personality disorders and other mental disorders. There are two free online personality tests that assess your personality in terms of the "Big 5 dimensions of personality.

This website uses these 5 major dimensions of human behavior to describe all mental disorders. (This website adds one more dimension, "Physical Health", but our discussion will focus on the first 5 major dimensions.)

These 5 major dimensions of human behavior seem to represent 5 major dimensions whereby our early ancestors chose their hunting companions or spouse. To maximize their chance for survival, our ancestors wanted companions who were agreeable, conscientious, intelligent, enthusiastic, and calm.

    Which Dimensions of Human Behavior are Impaired in Bipolar I Disorder, Manic Episode?

    THE POSITIVE SIDE OF THE "BIG 5" PERSONALITY DIMENSIONS THE NEGATIVE SIDE OF THE "BIG 5" PERSONALITY DIMENSIONS DESCRIPTION (Where red = this disorder)
    Agreeableness Antagonism       Sympathetic, Kind vs. Critical, Quarrelsome
    Conscientiousness Disinhibition       Industrious, Orderly vs. Impulsive, Disorderly
    Openness To Experience Impaired Intellect       Open-Minded, Creative vs. Psychotic
    Sociability (Extraversion) Detachment       Enthusiastic, Assertive vs. Reserved, Quiet
    Emotional Stability Negative Emotion       Calm, Emotionally Stable vs. Distressed, Easily Upset

    (Note: The behavior of individuals between mood episodes is normal.)


The 5 Major Dimensions of Mental Illness

Our website uses the "Big 5 Factors" of personality as major dimensions of mental illness. Each of these 5 dimensions has a healthy side and an unhealthy side. The Big 5 Factors are: Agreeableness, Conscientiousness, Openness to Experience, Sociability (Extraversion), and Emotional Stability. Our website adds an additional factor, Physical Health. However, our discussion will primarily focus on the traditional "Big 5 Factors".



The Following Pictures Are of The International Space Station

AGREEABLENESS VS. ANTAGONISM
.
Agreeableness (Sympathetic, Kind)
.
Description: Agreeableness is synonymous with compassion and politeness; whereas Antagonism is synonymous with competition and aggression. Compassion reflects empathy, sympathy, and caring for others. Politeness reflects respect for others’ needs and desires and a tendency to refrain from aggression. The Agreeableness dimension measures the behaviors that are central to the concept of LOVE and JUSTICE.
Descriptors: Compassionate, polite, kind, sympathetic, appreciative, affectionate, soft-hearted, warm, generous, trusting, helpful, forgiving, pleasant, good-natured, friendly, cooperative, gentle, unselfish, praising, sensitive.
MRI Research*: Agreeableness was associated with increased volume in regions that process information about the intentions and mental states of other individuals.
"I am helpful and unselfish with others."
"I have a forgiving nature."
"I am generally trusting."
"I am considerate and kind to almost everyone."
"I like to cooperate with others."
"I don't find fault with others."
"I don't start quarrels with others."
"I am not cold and aloof."
"I am not rude to others."
"I feel other's emotions."
"I inquire about others' well-being."
"I sympathize with others' feelings."
"I take an interest in other people's lives."
"I like to do things for others."
"I respect authority."
"I hate to seem pushy."
"I avoid imposing my will on others."
"I rarely put people under pressure."
.
Antagonism (Critical, Quarrelsome) [DURING MANIC EPISODES]
.
* Callousness:
"It's no big deal if I hurt other people's feelings."
"Being rude and unfriendly is just a part of who I am."
"I often get into physical fights."
"I enjoy making people in control look stupid."
"I am not interested in other people's problems."
"I can't be bothered with other's needs."
"I am indifferent to the feelings of others."
"I don't have a soft side."
"I take no time for others."
.
* Deceitfulness:
"I don't hesitate to cheat if it gets me ahead."
"Lying comes easily to me."
"I use people to get what I want."
"People don't realize that I'm flattering them to get something."
.
* Manipulativeness:
"I use people to get what I want."
"It is easy for me to take advantage of others."
"I'm good at conning people."
"I am out for my own personal gain."
.
* Grandiosity:
"I'm better than almost everyone else."
"I often have to deal with people who are less important than me."
"To be honest, I'm just more important than other people."
"I deserve special treatment."
.
* Suspiciousness:
"It seems like I'm always getting a “raw deal” from others."
"I suspect that even my so-called 'friends' betray me a lot."
"Others would take advantage of me if they could."
"Plenty of people are out to get me."
"I'm always on my guard for someone trying to trick or harm me."
.
* Hostility:
"I am easily angered."
"I get irritated easily by all sorts of things."
"I am usually pretty hostile."
"I always make sure I get back at people who wrong me."
"I resent being told what to do, even by people in charge."
"I insult people."
"I seek conflict."
"I love a good fight."
.
("Agreeableness vs. Antagonism" modified from "PID-5" by Kreuger RF, Derringer J, Markon KE, Watson D, Skodol AE and Between facets and domains: 10 aspects of the Big Five)
*MRI Research: Testing predictions from personality neuroscience. Brain structure and the big five.




CONSCIENTIOUSNESS VS. DISINHIBITION
.
Conscientiousness (Industrious, Orderly)
.
Description: Conscientiousness is synonymous with being industrious and orderly; whereas Disinhibition is synonymous with being impulsive and disorderly. The Conscientiousness dimension measures the behaviors that are central to the concept of SELF-CONTROL.
Descriptors: Self-disciplined, achievement-oriented, industrious, competent, reliable, responsible, orderly, deliberate, decisive
MRI Research*: Conscientiousness was associated with increased volume in the lateral prefrontal cortex, a region involved in planning and the voluntary control of behavior.
"I do a thorough job. I want everything to be 'just right'. I want every detail taken care of."
"I am careful."
"I am a reliable hard-worker."
"I am organized. I follow a schedule and always know what I am doing."
"I like order. I keep things tidy."
"I see that rules are observed."
"I do things efficiently. I get things done quickly."
"I carry out my plans and finish what I start."
"I am not easily distracted."
.
Rigid Perfectionism (Excessive Conscientiousness)
.
"Even though it drives other people crazy, I insist on absolute perfection in everything I do."
"I simply won't put up with things being out of their proper places."
"People complain about my need to have everything all arranged."
"People tell me that I focus too much on minor details."
"I have a strict way of doing things."
"I postpone decisions."
.
Disinhibition (Impulsive, Disorderly) [DURING MANIC EPISODES]
.
* Irresponsibility:
"I've skipped town to avoid responsibilities."
"I just skip appointments or meetings if I'm not in the mood."
"I'm often pretty careless with my own and others' things."
"Others see me as irresponsible."
"I make promises that I don't really intend to keep."
"I often forget to pay my bills."
.
* Impulsivity:
"I usually do things on impulse without thinking about what might happen as a result."
"Even though I know better, I can't stop making rash decisions."
"I feel like I act totally on impulse."
"I'm not good at planning ahead."
.
* Distractibility:
"I can't focus on things for very long."
"I am easily distracted."
"I have trouble pursuing specific goals even for short periods of time."
"I can't achieve goals because other things capture my attention."
"I often make mistakes because I don't pay close attention."
"I waste my time ."
"I find it difficult to get down to work."
"I mess things up."
"I don't put my mind on the task at hand."
.
* Reckless Risk Taking:
"I like to take risks."
"I have no limits when it comes to doing dangerous things."
"People would describe me as reckless."
"I don't think about getting hurt when I'm doing things that might be dangerous."
.
* Hyperactivity:
"I move excessively (e.g., can't sit still; restless; always on the go)."
"I'm starting lots more projects than usual or doing more risky things than usual."
.
* Over-Talkativeness:
"I talk excessively (e.g., I butt into conversations; I complete people's sentences)."
"Often I talk constantly and cannot be interrupted."
.
* Elation:
"I feel much more happy, cheerful, or self-confident than usual."
"I'm sleeping a lot less than usual, but I still have a lot of energy."
.
("Conscientiousness vs. Disinhibition" modified from "PID-5" by Kreuger RF, Derringer J, Markon KE, Watson D, Skodol AE and Between facets and domains: 10 aspects of the Big Five)
*MRI Research: Testing predictions from personality neuroscience. Brain structure and the big five.




OPENNESS TO EXPERIENCE vs. IMPAIRED INTELLECT
.
Open To Experience (Open-Minded, Creative)
.
Description: Open to Experience is synonymous with being open-minded and creative; whereas Closed to Experience is synonymous with being closed-minded and uncreative. The Openness to Experience dimension measures the behaviors that are central to the concept of WISDOM. Open-minded people ask "why?", are willing to challenge something that doesn't seem right, to listen to other people's opinions, and to be ever-ready to accept new truths, if the evidence is there. They are creative, flexible, and holistic in their thinking. They never stop questioning.
Descriptors: Wide interests, imaginative, intelligent, original, insightful, curious, sophisticated, artistic, clever, inventive, sharp-witted, wise
MRI Research*: Openness To Experience did not have any significant correlation with the volume of any brain structures. (This could suggest that "Openness To Experience", as defined here, is more a function of culture rather than of brain neurobiology.)
Example: This video shows how we see what we want to see. What we pay attention to (or what we believe about the world) blinds us to reality. (Exit YouTube after first video.)
"I am original, and come up with new ideas."
"I am curious about many different things."
"I am quick to understand things."
"I can handle a lot of information."
"I like to solve complex problems."
"I have a rich vocabulary."
"I think quickly and formulate ideas clearly."
"I enjoy the beauty of nature."
"I believe in the importance of art."
"I love to reflect on things."
"I get deeply immersed in music."
"I see beauty in things that others might not notice."
"I need a creative outlet."
.
Closed To Experience (Closed-Minded, Uncreative)
.
"I prefer work that is routine."
"I have difficulty understanding abstract ideas."
"I avoid philosophical discussions."
"I avoid difficult reading material."
"I learn things slowly."
"I have few artistic interests."
"I seldom notice the emotional aspects of paintings and pictures."
"I do not like poetry."
"I seldom get lost in thought."
"I seldom daydream."
.
Cognitive Impairment [DURING PSYCHOTIC EPISODES]
.
* Memory Impairment:
"I have difficulty learning new things, or remembering things that happened a few days ago."
"I often forget a conversation I had the day before."
"I often forget to take my medications, or to keep my appointments."
.
.
* Impaired Reasoning or Problem-Solving:
"My judgment, planning, or problem-solving isn't good."
"I lack creativity or curiosity."
.
Psychoticism
.
* Eccentricity:
"I often have thoughts that make sense to me but that other people say are strange."
"Others seem to think I'm quite odd or unusual."
"My thoughts are strange and unpredictable."
"My thoughts often don’t make sense to others."
"Other people seem to think my behavior is weird."
"I have several habits that others find eccentric or strange."
"My thoughts often go off in odd or unusual directions."
.
* Unusual Beliefs and Experiences:
"I often have unusual experiences, such as sensing the presence of someone who isn't actually there."
"I've had some really weird experiences that are very difficult to explain."
"I have seen things that weren’t really there."
"I have some unusual abilities, like sometimes knowing exactly what someone is thinking."
"I sometimes have heard things that others couldn’t hear."
"Sometimes I can influence other people just by sending my thoughts to them."
"I often see unusual connections between things that most people miss."
.
* Perceptual Dysregulation:
"Things around me often feel unreal, or more real than usual."
"Sometimes I get this weird feeling that parts of my body feel like they're dead or not really me."
"It's weird, but sometimes ordinary objects seem to be a different shape than usual."
"Sometimes I feel 'controlled' by thoughts that belong to someone else."
"Sometimes I think someone else is removing thoughts from my head."
"I have periods in which I feel disconnected from the world or from myself."
"I can have trouble telling the difference between dreams and waking life."
"I often 'zone out' and then suddenly come to and realize that a lot of time has passed."
"Sometimes when I look at a familiar object, it's somehow like I'm seeing it for the first time."
"People often talk about me doing things I don't remember at all."
"I often can't control what I think about."
"I often see vivid dream-like images when I’m falling asleep or waking up."
.
("OPENNESS TO EXPERIENCE vs. BEING CLOSED TO EXPERIENCE" modified from "PID-5" by Kreuger RF, Derringer J, Markon KE, Watson D, Skodol AE and Between facets and domains: 10 aspects of the Big Five)
*MRI Research: Testing predictions from personality neuroscience. Brain structure and the big five.




SOCIABILITY (EXTRAVERSION) vs. DETACHMENT
.
Sociability (Enthusiastic, Assertive)
.
Description: Sociability is synonymous with being enthusiastic and assertive; whereas Detachment is synonymous with being reserved and quiet. Assertiveness encompasses traits relating to leadership, dominance, and drive. Enthusiasm encompasses both outgoing friendliness or sociability and the tendency to experience and express positive emotion. The Sociability (Extraversion) dimension measures the behaviors that are central to the concept of SOCIABILITY and LEADERSHIP.
Descriptors: Enthusiastic, assertive, sociable, outgoing, talkative, active, energetic, outspoken, dominant, forceful, show-off, spunky, adventurous, noisy, bossy.
MRI Research*: Sociability (extraversion) was associated with increased volume of medial orbitofrontal cortex, a region involved in processing reward information.
"I'm talkative"
"I'm not reserved."
"I'm full of energy."
"I generate a lot of enthusiasm."
"I'm not quiet."
"I have an assertive personality."
"I'm not shy or inhibited."
"I am outgoing and sociable."
"I make friends easily."
"I warm up quickly to others."
"I show my feelings when I'm happy."
"I have a lot of fun."
"I laugh a lot."
"I take charge."
"I have a strong personality."
"I know how to captivate people."
"I see myself as a good leader."
"I can talk others into doing things."
"I am the first to act."
.
Attention Seeking (Excessive Sociability) [DURING MANIC EPISODES]
.
"I like to draw attention to myself."
"I crave attention."
"I do things to make sure people notice me."
"I do things so that people just have to admire me."
"My behavior is often bold and grabs peoples' attention."
.
Detachment (Reserved, Quiet) [DURING DEPRESSIVE EPISODES]
.
* Social Withdrawal:
"I don’t like to get too close to people."
"I don't deal with people unless I have to."
"I'm not interested in making friends."
"I don’t like spending time with others."
"I say as little as possible when dealing with people."
"I keep to myself."
"I am hard to get to know."
"I reveal little about myself."
"I do not have an assertive personality."
"I lack the talent for influencing people."
"I wait for others to lead the way."
"I hold back my opinions."
.
* Intimacy Avoidance:
"I steer clear of romantic relationships."
"I prefer to keep romance out of my life."
"I prefer being alone to having a close romantic partner."
"I'm just not very interested in having sexual relationships."
"II break off relationships if they start to get close."
.
* Anhedonia (Lack of Pleasure):
"I often feel like nothing I do really matters."
"I almost never enjoy life."
"Nothing seems to make me feel good."
"Nothing seems to interest me very much."
"I almost never feel happy about my day-to-day activities."
"I rarely get enthusiastic about anything."
"I don't get as much pleasure out of things as others seem to."
.
* Restricted Emotions:
"I don't show emotions strongly."
"I don't get emotional."
"I never show emotions to others."
"I don't have very long-lasting emotional reactions to things."
"People tell me it's difficult to know what I'm feeling."
"I am not a very enthusiastic person."
.
("Sociability vs. Detachment" modified from "PID-5" by Kreuger RF, Derringer J, Markon KE, Watson D, Skodol AE and Between facets and domains: 10 aspects of the Big Five)
*MRI Research: Testing predictions from personality neuroscience. Brain structure and the big five.




EMOTIONAL STABILITY VS. NEGATIVE EMOTION
.
Emotional Stability (Calm, Emotionally Stable)
.
Description: Emotional Stability is synonymous with being calm and emotionally stable; whereas Negative Emotion is synonymous with being distressed and easily upset. The Emotional Stability dimension measures the "safety vs. danger" behaviors that are central to the concept of COURAGE.
Descriptors: Stable, calm, relaxed, contented
"I am relaxed, and I handle stress well."
"I am emotionally stable, and not easily upset."
"I remain calm in tense situations."
"I rarely get irritated."
"I keep my emotions under control."
"I rarely lose my composure."
"I am not easily annoyed."
"I seldom feel blue."
"I feel comfortable with myself."
"I rarely feel depressed."
"I am not embarrassed easily."
.
Negative Emotion (Distressed, Easily Upset) [DURING MOOD EPISODES]
.
Description: Degree to which people experience persistent negative emotions (anxiety, anger, or depression) and are easily upset. (This could be thought of as high threat sensitivity or low stress tolerance.)
Descriptors: Emotional instability, anxiety, irritability, depression, rumination-compulsiveness, self-consciousness, vulnerability
MRI Research*: Negative Emotion was associated with increased volume of brain regions associated with threat, punishment, and negative emotions.
.
* Emotional Instability:
"I get emotional easily, often for very little reason."
"I get emotional over every little thing."
"My emotions are unpredictable."
"I never know where my emotions will go from moment to moment."
"I am a highly emotional person."
"I have much stronger emotional reactions than almost everyone else."
"My emotions sometimes change for no good reason."
"I get angry easily."
"I get upset easily."
"I change my mood a lot."
"I am a person whose moods go up and down easily."
"I get easily agitated."
"I can be stirred up easily."
.
* Anxiety:
"I worry about almost everything."
"I'm always fearful or on edge about bad things that might happen."
"I always expect the worst to happen."
"I am a very anxious person."
"I get very nervous when I think about the future."
"I often worry that something bad will happen due to mistakes I made in the past."
"I am filled with doubts about things."
"I feel threatened easily."
"I am afraid of many things."
.
* Separation Insecurity:
"I fear being alone in life more than anything else."
"I can't stand being left alone, even for a few hours."
"I’d rather be in a bad relationship than be alone."
"I'll do just about anything to keep someone from abandoning me."
"I dread being without someone to love me."
.
* Submissiveness:
"I usually do what others think I should do."
"I do what other people tell me to do."
"I change what I do depending on what others want."
.
* Perseveration:
"I get stuck on one way of doing things, even when it's clear it won't work."
"I get stuck on things a lot."
"It is hard for me to shift from one activity to another."
"I get fixated on certain things and can’t stop."
"I feel compelled to go on with things even when it makes little sense to do so."
"I keep approaching things the same way, even when it isn’t working."
.
* Depressed Mood:
"I have no worth as a person."
"Everything seems pointless to me."
"I often feel like a failure."
"The world would be better off if I were dead."
"The future looks really hopeless to me."
"I often feel just miserable."
"I'm very dissatisfied with myself."
"I often feel like nothing I do really matters."
"I know I'll commit suicide sooner or later."
"I talk about suicide a lot."
"I feel guilty much of the time."
"I'm so ashamed by how I've let people down in lots of little ways."
"I am easily discouraged."
"I become overwhelmed by events."
.
("Emotional Stability vs. Negative Emotion" modified from "PID-5" by Kreuger RF, Derringer J, Markon KE, Watson D, Skodol AE and Between facets and domains: 10 aspects of the Big Five)
*MRI Research: Testing predictions from personality neuroscience. Brain structure and the big five.



The "Big 5 Factors" of Personality as Shown In Dogs

The same "Big 5 Factors" of personality found in humans can be found in dogs. This makes sense because dogs, like humans, are a social species.



AGREEABLENESS VS. ANTAGONISM
.
Agreeableness ("Friend")
.
Dog is friendly towards unfamiliar people.
Dog is friendly towards other dogs.
When off leash, dog comes immediately when called.
Dog willingly shares toys with other dogs.
Dog leaves food or objects alone when told to do so.
.
Antagonism ("Foe")
.
Dog is dominant over other dogs.
Dog is assertive with other dogs (e.g., if in a home with other dogs, when greeting).
Dog behaves aggressively towards unfamiliar people.
Dog shows aggression when nervous or fearful.
Dog aggressively guards coveted items (e.g., stolen item, treats, food bowl).
Dog is quick to sneak out through open doors, gates.

CONSCIENTIOUSNESS VS. DISINHIBITION
.
Conscientiousness ("Self-Controlled")
.
Dog works at tasks (e.g., getting treats out of a dispenser, shredding toys) until entirely finished.
Dog works hard all day herding or pulling a sleigh (if a "working dog" on the farm or in the snow).*
Dog is curious.
.
Disinhibition ("Disinhibited")
.
Dog is boisterous.
Dog seeks constant activity.
Dog is very excitable around other dogs.

OPENNESS TO EXPERIENCE vs. IMPAIRED INTELLECT
.
Open To Experience ("Open-Minded")
.
Dog is able to focus on a task in a distracting situation (e.g., loud or busy places, around other dogs).
.
Closed To Experience ("Closed-Minded")
.
Dog is slow to respond to corrections.
Dog ignores commands.
Dog is slow to learn new tricks or tasks.

SOCIABILITY (EXTRAVERSION) vs. DETACHMENT
.
Sociability ("Approach")
.
Dog is attention seeking (e.g., nuzzling, pawing or jumping up on family members looking for attention and physical contact).*
Dog seeks companionship from people.
Dog is affectionate.
.
Detachment ("Avoidance")
.
Dog is aloof.
Dog gets bored in play quickly.
Dog is lethargic.

EMOTIONAL STABILITY VS. NEGATIVE EMOTION
.
Emotional Stability ("Safety")
.
Dog tends to be calm.
Dog is relaxed when greeting people.
Dog is confident.
Dog adapts easily to new situations and environments.
.
Negative Emotion ("Danger")
.
Dog is anxious.
Dog is shy.
Dog behaves fearfully towards unfamiliar people.
Dog exhibits fearful behaviors when restrained.
Dog avoids other dogs.
Dog behaves fearfully towards other dogs.
Dog behaves submissively (e.g., rolls over, avoids eye contact, licks lips) when greeting other dogs.
.
Modified from Jones, A. C. (2009). Development and validation of a dog personality questionnaire. Ph.D. Thesis. University of Texas, Austin.

* New items added by Phillip W. Long MD

Notice the Personality Differences Between Dogs and Humans

Dogs and humans are strikingly similar on 4 of the "Big 5 Factors" of personality. However, dogs and humans are quite different on the "Conscientiousness" factor - because the canine brain isn't designed to organize work projects. That's why dogs don't build dog houses.

Two of the "Big 5 Factors" of dog personality are clearly a function of dogs being a social species that forms social hierarchies: (1) the "Agreeableness" factor describes "friend vs. foe" behaviors, and (2) the "Sociability" factor describes "approach vs. avoidance" behaviors.

The "Openness to Experience" describes the ability to learn from experience. The "Emotional Stability" factor describes "safety vs. danger" behaviors.

The Brain and the "Big-5 Factors" of Human and Dog Personality

It could be that the "Big-5 Factors" of personality represent some extremely basic brain functions. For example, when a young man approaches a young woman, she must: (1) decide whether he is friend or foe ["Agreeableness"], (2) decide if this represents safety or danger ["Emotional Stability"], (3) decide whether to approach or avoid him ["Sociability"], (4) decide whether to be self-controlled or disinhibited ["Conscientiousness"], and (5) learn from this experience ["Openness to Experience"].


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World Health Organization Bipolar Disorder Treatment Guidelines

(Note: WHO realizes that most of the world can't afford over-priced atypical antipsychotic medication.)

















World Health Organization Depression Treatment Guidelines

Treatment Guidelines

Treatment

Summary Of Clinical Practice Guideline: Management Of Bipolar Disorder In Adults - U.S. Department Of Veterans Affairs (2010)

Strength of Recommendations Rating System

A A strong recommendation that the clinicians provide the intervention to eligible patients.
Good evidence was found that the intervention improves important health outcomes and concludes that benefits substantially outweigh harm.
B A recommendation that clinicians provide (the service) to eligible patients.
At least fair evidence was found that the intervention improves health outcomes and concludes that benefits outweigh harm.
C No recommendation for or against the routine provision of the intervention is made.
At least fair evidence was found that the intervention can improve health outcomes, but concludes that the balance of benefits and harms is too close to justify a general recommendation.
D Recommendation is made against routinely providing the intervention to asymptomatic patients.
At least fair evidence was found that the intervention is ineffective or that harms outweigh benefits.
I The conclusion is that the evidence is insufficient to recommend for or against routinely providing the intervention.
Evidence that the intervention is effective is lacking, or poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Major Recommendations

Module A: Bipolar Acute Manic, Hypomanic, or Mixed Episode

A-1. Person Meets Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) Criteria for Bipolar Manic, Hypomanic, or Mixed Episode

Refer to the original guideline document for definitions of manic, hypomanic and mixed episodes.

A-2. Complete Assessment; Review Current Medication; Assess Suicide Risk

Action Statement

Patients with a bipolar mania, hypomania or mixed episode require a thorough evaluation to determine level of risk and appropriate acute treatment.

Recommendations

  1. A complete clinical assessment should be obtained for patients with a manic, hypomanic, or mixed episode to include:
    1. Clinical status
    2. Medical comorbidities
    3. Psychiatric comorbidities
    4. Psychosocial status
    5. Current medications
    6. Past medications
    7. Medication compliance
    8. Substance use
  1. A standardized tool combined with a clinical interview should be used to obtain the necessary information about symptoms, symptom severity, and effects on daily functioning that is required to diagnose bipolar disorder (BD) mania/hypomania based on DSM-IV-TR criteria.
  2. Assess the severity of mania episode using a standardized rating scale (e.g., Young Mania Rating Scale).
  3. Consider using the same standardized questionnaire to monitor treatment response at follow-up visits, after each change in treatment, and to periodically assess the patient’s response to treatment until full remission is achieved.

For further information on assessment and screening tools for BD and suicide.

A-3. Is Patient Taking Antidepressants or Mania-Inducing Medication? Reduce/Stop Antidepressant Medications

Action Statement

Stop manic-inducing medications in patients who are experiencing a manic, hypomanic or mixed manic episode.

Recommendations

  1. Antidepressants or other manic inducing substances should be stopped in patients experiencing a manic, hypomanic, or mixed manic episode. [B]
  2. Antidepressant medications known to be associated with discontinuation syndromes may be tapered over 3 to 5 days rather than being abruptly stopped. [C]

The most common discontinuation symptoms include:

  • Dizziness
  • Headache
  • Paresthesia
  • Nausea
  • Diarrhea
  • Insomnia
  • Irritability

A-4. Severe Mania, Dangerousness, or Psychotic Features Present?

Recommendations

  1. Patients with BD mania, hypomania, or mixed episode should be assessed for suicidality, acute or chronic psychosis or other unstable or dangerous conditions.
  2. Any patient with suicidal ideation or suicide attempts necessitating psychiatric hospitalization should be considered for referral to mental health specialty care. (See Appendix B: "Assessment of Dangerous to Self or Others," in the original guideline document).
  3. Patients with a diagnosis of BD mania who present with severe symptoms with any of the following unstable conditions, need to be referred for urgent/emergent mental health intervention as these are inappropriate for care in the primary care setting:
    1. Delirium
    2. Marked psychotic symptoms
    3. Severe mania symptoms
    4. Suicidality or homicidality
    5. Potential for violence (e.g., ideas about or intent to harm others; history of violent behavior; severe agitation or hostility; active psychosis)
    6. Substance withdrawal or intoxication

A-5. Refer for Hospitalization

Action Statement

Ensure that appropriate care, protocols, and regulatory/policy mandates are followed during diagnosis and stabilization of the patient with a severe or an unstable bipolar manic episode.

Recommendations

  1. Local, state and federal regulations/mandates, as well as guidelines, should be followed when the patient represents a risk to self or others.
  2. Patients with urgent, unstable conditions, severe mania or mixed episode or elevated dangerousness should be referred to a higher level of care (hospitalization).
  3. Hospitalization should be considered in patients whose severe mania or mixed episode seriously impairs their ability to care for themselves. [I]

A-6. Initiate/Adjust Treatment with Combination of Anti-Psychotic and Anti-Manic Medications

Action Statement

Patients with severe mania or mixed episode, with or without psychotic features, should be started on a combination of an antipsychotic and another anti-manic agent.

Recommendations

  1. Patients with severe mania should be treated with a combination of antipsychotics and lithium or valproate. These antipsychotics include olanzapine, quetiapine, aripiprazole, or risperidone [B] and may include ziprasidone. [I]
  2. Patients with severe mixed episode should be treated with a combination of antipsychotics and lithium or valproate. These antipsychotics include aripiprazole, olanzapine, risperidone, or haloperidol [B] and may include quetiapine or ziprasidone. [I]
  3. Clozapine, with its more serious side effect profile, may be added to existing medications for severe mania or mixed episode if it has been successful in the past or if other antipsychotics have failed. [I]
  4. Patients who are not hospitalized should be reassessed every 2 to 5 days until symptoms improve.

A-7. Is Patient Receiving Clinical Effective Medications for Bipolar Mania/Mixed?

For recommended medications see Annotation A-9.

A-8. Modify Dose of Medication As Needed

Action Statement

Adjust anti-manic agents to minimize adverse effects while maximizing clinical effectiveness and maintaining therapeutic plasma concentrations when those are known.

Recommendations

  1. If patient is having intolerable side effects switch to another effective treatment. [I]
  2. Assess compliance and blood serum concentration to assess if medications are in therapeutic range: [I]
    1. The serum trough concentration of lithium should be maintained between 0.8-1.2 mEq/L
    2. The serum trough concentration of valproate should be maintained between 50-125 mcg/ml
    3. The serum trough concentration of carbamazepine should be maintained between 4–12 mcg/ml
  1. Medications without known therapeutic plasma concentrations should be increased until significant improvement is seen, side effects become intolerable or the dose reaches the manufacturer’s suggested upper limits. [I]

A-9. Initiate/Adjust Treatment with an Anti-Manic Medication

Action Statement

Patients with mania/hypomania or mixed episode should be started on a medication proven to effectively treat manic and mixed manic symptoms.

Recommendations

General Considerations

  1. Pharmacotherapy for bipolar mania or mixed episode should start with initiation or optimization of a medication that has been shown to be the most effective in treating bipolar manic episodes while minimizing the potential risks. [I] (see Table A - 2 in the original guideline document)
  2. Consider using the agent(s) that have been effective in treating prior episodes of mania or mixed episode. [I]
  3. Ensure that the patient has stopped taking any antidepressant or mania inducing substances. [B]
  4. In selecting a drug treatment regimen for patients with BD, clinicians should be aware of the patient's other psychiatric and medical conditions and should try to avoid exacerbating them.
  5. In selecting a drug treatment regimen for patients with diabetes or obesity consider the risk and benefit of utilizing medications that are less associated with weight gain.

Mania

  1. Patients with mania should be started on one of the following: lithium, valproate, carbamazepine, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. [A]

Mixed Episode

  1. Patients with mixed episode should be started on one of the following: valproate, carbamazepine, olanzapine, aripiprazole, risperidone, or ziprasidone. [A]

Mania or Mixed Episode

  1. Clozapine, haloperidol and oxcarbazepine may be considered in patients with mania or mixed episode. [I]
  2. Lithium or quetiapine may be considered in patients with mixed episode. [I]
  3. Medications NOT recommended in patients with mania or mixed episode include topiramate, lamotrigine, and gabapentin. [D]

A-10. Reassess Every One to Two Weeks for at Least 6 Weeks

Recommendations

  1. Ongoing assessment of patients starting treatment for acute bipolar mania, hypomania or mixed episodes should include a reassessment for: [I]
    1. The development of depressive symptoms, suicidal ideation or homicidal ideation
    2. Emergence or change in psychotic symptoms
    3. Substance use
    4. Adverse effects of medications (See Table E - 1 "Adverse Events – Lithium"; Table E - 4 "Adverse Events Antiepileptic Medications"; and Table E - 6 "Adverse Events - Antipsychotics" in the original guideline document)
    5. Medication adherence
    6. Medical stability (e.g., blood pressure)
    7. Significant changes in psychosocial circumstances
  1. Reassess patient every 1 to 2 weeks for at least 6 weeks. [I]
  2. Ongoing assessment of patients starting treatment for acute bipolar mania or mixed episode may include pertinent laboratory studies (e.g., medication plasma concentrations, urine drug screening, complete blood count [CBC], blood glucose, liver panel, lipid panel) and weight.

A-11. Is Patient Responding to Therapy?

Recommendations

  1. Monitor treatment response at 4 to 8 weeks after initiation of treatment, after each change in treatment, and periodically until full remission is achieved. [B]
  2. In patients who reach full remission, assessment of symptoms should be continued periodically to monitor for relapse or recurrence. [B]
  3. Patients with suicidal ideation should have a careful evaluation of suicide risk. [A]
  4. Providers should give simple educational messages regarding medication therapy (e.g., take daily, understand gradual nature of benefits, continue even when feeling better, do not stop without checking with the provider, and specific instructions on how to address issues or concerns) in order to increase adherence to treatment. [I]
  5. Patient, family and/or caregiver should be educated about the risk of relapse to mania or hypomania that may occur. They should be instructed on identifying symptoms and the importance of contacting their provider immediately if they notice these symptoms. [I]

A-12. Is Patient in Full Remission?

Recommendations

  1. Patients with mania who have been without any significant symptoms of mania for two months should be considered to be in full remission. [I]
  2. Patients with mixed episode who have been without any significant symptoms of mania or depression for two months should be considered to be in full remission. [I]

A-13. Assess Adherence, Need for Psychosocial and/or Family Interventions, Adverse Effects, and Psychosocial Barriers to Therapy; Assess Risk for Suicide

Action Statement

Assess adherence to therapy, and other possible causes for partial response or non-response.

Recommendations

  1. Patients should be followed by a scheduled visit to the clinic periodically, depending on their response to therapy, for a thorough assessment that includes:
    1. Adherence to therapy. Reasons for noncompliance should be explored with the patient. [A]
    2. Assessment of potential adverse effects. [A] (see Table E - 1 "Adverse Events – Lithium"; Table E - 4 "Adverse Events Antiepileptic Medications"; and Table E - 6 "Adverse Events - Antipsychotics," in the original guideline document).
    3. Monitoring of serum concentration for lithium, valproate, or carbamazepine, and other appropriate blood work to maintain efficacy and avoid toxicity [A/B] (See Annotation A-8)
    4. For patients receiving antipsychotic medications, monitor weight, body mass index (BMI), waist circumference, blood pressure, plasma glucose and fasting lipids [A]. (See Table E-8 "Monitoring Parameters for Metabolic Adverse Effects in Second Generation Antipsychotics," in the original guideline document).
    5. Assessment of any changes in patient's family and community support (housing, care givers, employment, income, social networks). [B]
  1. Assess for improvement or change of the core symptoms of mania and mixed episode through a clinical interview or the use of a standardized rating scale (e.g., Young Mania Rating Scale). [I]
  2. Patients with suicidal ideation should have a careful evaluation of suicide risk. [A]

A-14. Add/Change Anti Manic Medication until Stable or Consider Alternative Therapy

Action Statement

Patients whose mania or mixed episode does not respond to adequate doses of a single medication should be receiving more aggressive medication treatment or hospitalization.

Recommendations

  1. Patients whose mania does not respond to monotherapy should be considered for consultation/referral with specialty care. (For patient with severe mania or mixed episode – see Annotation A-6.)
  2. Reassess for co-occurring medical conditions that may also contribute to greater bipolar illness severity and reduced recovery. [C]
  3. Escalating pharmacotherapy may be considered for patients whose mania/mixed episode or hypomania does not respond to monotherapy. The possible options for escalating pharmacotherapy include:
    1. Switching to another monotherapy may be considered if the patient did not respond to the first medication. [I]
    2. In patients with mania/hypomania who do not respond to monotherapy, consider combining a non-antipsychotic mood stabilizer (lithium or valproate) with a second generation antipsychotic such as aripiprazole, olanzapine, quetiapine, or risperidone [A] or ziprasidone. [I]
    3. In patients with mixed episode who do not respond to monotherapy, consider a combination of non-antipsychotics mood stabilizer (lithium or valproate) and a second generation antipsychotic such as aripiprazole, olanzapine, or risperidone [B] or quetiapine or ziprasidone. [I]
  1. Clozapine, with its more serious side effect profile, may be combined with valproate or lithium as a treatment of severe mania or mixed episode, if it has been successful in the past or if other antipsychotics have failed. [I]
  2. Adjust medications if there is no response within 2 to 4 weeks on an adequate dose of medication.
  3. Electroconvulsive therapy (ECT) may be considered for patients with severe mania or patients whose mania is treatment resistant, those patients who express a preference for ECT, and patients with severe mania during pregnancy. [C]
  4. Risks and benefits of long-term pharmacotherapy should be discussed prior to starting medication and should be a continued discussion item during treatment. [A]

Module B: Bipolar Acute Depressive Episode

B-1. Person Meets DSM-IV-TR Criteria for Bipolar Depressive Episode

Refer to the original guideline document for definition of a major depressive episode DSM-IV-TR.

B-2. Complete Assessment; Review Current Medications; Assess Suicide Risk

Action Statement

Patients with a bipolar depressive episode require a thorough evaluation to determine level of risk and appropriate treatment.

Recommendations

  1. A complete clinical assessment should be obtained for patients with BD depression episode to include:
    1. Clinical status
    2. Medical comorbidities
    3. Psychiatric comorbidities
    4. Psychosocial status
    5. Current medications
    6. Past medications
    7. Medication compliance
    8. Substance use

    See Appendix B: "Assessment of Dangerous to Self or Others," in the original guideline document.

  1. A standardized tool combined with a clinical interview should be used to obtain the necessary information about symptoms, symptom severity, and effects on daily functioning that is required to diagnose BD depression based on DSM-IV-TR criteria.
  2. Consider using the same standardized questionnaire to monitor treatment response at 4 to 6 weeks, after each change in treatment, and to periodically assess the patient's response to treatment until full remission is achieved.

B-3. Is The Patient at High Risk of Harming Self or Others?

Action Statement

Identify patients who are at high risk of harm to self or others.

Recommendations

  1. Patients with a possible diagnosis of BD depression should be assessed for suicidality, acute or chronic psychosis or other unstable or dangerous conditions.
  2. A referral to emergency services and/or a mental health professional is indicated for patients presenting with any of the following unstable conditions:
    1. Delirium
    2. Marked psychotic symptoms
    3. Severe depressive symptoms/depression (e.g., catatonia, malnourishment, severe disability)
    4. Suicidality or homicidality
    5. Potential for violence (e.g., ideas about or intent to harm others; history of violent behavior; severe agitation or hostility; active psychosis)
    6. Substance withdrawal or intoxication
  1. Any patient with suicidal or homicidal ideation or attempts necessitating psychiatric hospitalization should be considered for referral to mental health specialty care. (See Appendix B: "Dangerous to Self or Others," in the original guideline document).
  2. Patients with a possible diagnosis of BD depression who exhibit any of the following characteristics related to psychosis need to be referred for urgent/emergent mental health intervention as these are inappropriate for care in the primary care setting:
    1. Serious delusions (e.g., fixed false beliefs)
    2. Visual or (typically) auditory hallucinations
    3. Confusion (incoherence)
    4. Catatonic behavior (e.g., motor immobility or excessive agitation)
    5. Extreme negativism or mutism
    6. Peculiar voluntary movement
    7. Inappropriate affect of a bizarre or odd quality

B-4. Refer for Hospitalization

Action Statement

Ensure that appropriate care, protocols, and regulatory/policy mandates are followed during diagnosis and stabilization of the patient with an unstable bipolar depressive episode.

Recommendations

  1. Local, state and federal regulations/mandates as well as guidelines should be followed when the patient represents a risk to self or other.
  2. Patients with urgent, unstable conditions, severe depression or elevated dangerousness should be referred to a higher level of care (hospitalization).

B-5. Is Patient Currently Receiving Clinically Effective Medications for Bipolar Depression?

All patients with BD depression should be treated with medications that have been shown to be effective. For recommendation on modifying medication treatment see Annotation B-7.

B-6. Pharmacotherapy for Bipolar Depression

Action Statement

Patients with a bipolar depressive episode should be treated with medications that have demonstrated efficacy in treating that depressive episode while minimizing the risk of inducing a manic, hypomanic or mixed manic episode.

Recommendations

General Considerations

  1. Pharmacotherapy for bipolar depression should start with initiation or optimization of a medication that has been shown to be the most effective in treating bipolar depressive episodes, while minimizing the potential risks. [B] (see Table B-2 in the original guideline document.)
  2. Consider using the agent(s) that have been effective in treating prior episodes of depression. [I]
  3. The risk for mood destabilization or switching to mania should be evaluated and the patient should be monitored closely for emergent symptoms after initiation of pharmacotherapy for a depressive episode. [I]
  4. For patients with BD depression with psychotic features, an antipsychotic medication should be started. [I]
  5. Consider adding one of the evidence based psychotherapeutic interventions to improve adherence and patient outcome. [B] (See Module D: Psychosocial Interventions)
  6. In selecting a drug treatment regimen for patients with BD, clinicians should be aware of the patient’s other psychiatric and medical conditions and should try to avoid exacerbating them.
  7. In selecting a drug treatment regimen for patients with diabetes or obesity consider the risk and benefit of utilizing medications that are less associated with weight gain.

Monotherapy

  1. Quetiapine, [A], lamotrigine [B], or lithium [B] monotherapy should be considered as first-line treatment for adult patients with BD depression.
  2. Olanzapine/fluoxetine combination (OFC) should be considered for treatment of BD depression, but its adverse effects (weight gain, risk of diabetes, hypertriglyceridemia) places this combination as a second-line treatment. [B]
  3. Olanzapine alone may be considered for BD depression, but adverse effects require caution. [C]
  4. There is insufficient evidence to recommend for or against the use of valproate, carbamazepine, topiramate, risperidone, ziprasidone, or clozapine for BD depression. [I]
  5. Aripiprazole is NOT recommended for monotherapy in the treatment of acute bipolar depression, unless there is a history of previous good response during depression without switch to mania or a history of treatment refractory depression. [D]

Combination Strategies

  1. Combining lithium with lamotrigine can be considered for patients with BD depression who do not respond to monotherapy. [A]
  2. When patients do not respond to treatment options that have shown better efficacy, antidepressant augmentation with selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), bupropion, and monoamine oxidase inhibitor (MAOI) can be considered for short-term treatment, monitoring closely for triggering of manic symptoms. [C]
  3. Clozapine may be considered for augmentation, using caution regarding metabolic or other adverse effects. [I]
  4. There is insufficient evidence to recommend for or against use of augmentation with aripiprazole, olanzapine, risperidone, haloperidol, oxcarbazepine, topiramate, ziprasidone, valproate, or carbamazepine for the treatment of bipolar depression. [I]
  5. Gabapentin and the tricyclic antidepressants (TCAs) are NOT recommended for monotherapy or augmentation in the treatment of acute bipolar depression, unless there is a history of previous good response during depression without switch to mania or a history of treatment refractory depression. [D]

B-7. Modify Dose or Medication if Indicated, Using Medications Effective for Bipolar Depression

Recommendations

  1. If patient is having intolerable side effects switch to another effective treatment. [I]
  2. If the patient has switched into mania or hypomania or entered a mixed manic state, go to Module A (Acute Mania). [I]
  3. Assess compliance and blood serum concentration to assess if medications are in therapeutic range [I]
    1. The serum trough concentration of lithium should be maintained between 0.8-1.2 mEq/L.
    2. The serum trough concentration of valproate should be maintained between 50-125 mcg/ml.
    3. The serum trough concentration of carbamazepine should be maintained between 4–12 mcg/ml.
  1. If medication is not in therapeutic range, adjust medication to maximum range. [I]
  2. Medications without known therapeutic plasma concentrations should be increased until significant improvement is seen, side effects become intolerable or the dose reaches the manufacturer's suggested upper limits. [I]

Partial Response

  1. Adjust medications if there is no response within 2 to 4 weeks on an adequate dose of medication. Adjustment may include:
    1. Augmenting with additional agents (See Annotation B-6)
    2. Discontinue the current agent and switch to another effective medication (See Annotation B-6)
    3. If multiple trials of switching medications or augmentation strategies have not been effective consider ECT. [I]
  1. Any discontinuation of medication used to treat bipolar depression should be tapered and the patient should be monitored for antidepressant discontinuation syndrome and mood destabilization. [I]
  2. Risks and benefits of long term pharmacotherapy should be discussed prior to starting medication and should be a continuing discussion item during treatment. [A]

B-8. Reassess Every One to Two Weeks for Six Weeks

Recommendations

  1. Ongoing assessment of patients starting treatment for acute bipolar depression should include a reassessment for: [I]
    1. Changes in depressive symptoms
    2. Neurovegetative symptoms
    3. Emerging symptoms of mania/hypomania
    4. Psychotic symptoms
    5. Development of suicidal or homicidal ideation
    6. Substance use
    7. Adverse effects of medications
    8. Medication compliance
    9. Medical stability (e.g., blood pressure)
    10. Significant changes in psychosocial circumstances
  1. Reassess patient every 1 to 2 weeks for at least 6 weeks. [I]
  2. Ongoing assessment of patients starting treatment for acute bipolar depression may include pertinent laboratory studies (e.g., medication plasma concentrations, urine drug screening, complete blood count (CBC), blood glucose, liver panel, lipid panel) and weight. [I]

B-9. Provide Psychoeducation, Psychotherapy, and Family Intervention as Indicated

Recommendations

  1. Providers should give simple educational messages regarding medication therapy (e.g., take daily, understand gradual nature of benefits, continue even when feeling better, do not stop without checking with the provider, and specific instructions on how to address issues or concerns) in order to increase adherence to treatment. [B]
  2. Patient, family and/or caregiver should be educated about the risk of switching to mania or hypomania that may occur naturally or as a result of medications. They should be instructed on identifying symptoms and the importance of contacting their provider immediately if they notice these symptoms. [I]
  3. Consider psychoeducation and care management for patients with BD. [B] For best effect consider offering in a structured group setting with ongoing care/disease management. [A]
  4. Patients who are currently in a depressive episode and are at high risk for non-adherence to medication, should be considered for one of the following evidence-based psychotherapeutic interventions
    1. Cognitive behavioral therapy (CBT) [A]
    2. Family Therapy [B]
    3. Interpersonal and Social Rhythm Therapy (IPSRT) [B]

B-10. Is Patient Responding to Treatment?

Recommendations

  1. Once the patient has demonstrated a response to treatment, continue to monitor progress every 4 to 8 weeks and after each change in treatment until full remission is achieved. [B]
  2. In patients who reach full remission, assessment of symptoms should be continued periodically to monitor for relapse or recurrence. [B]
  3. Patients with suicidal ideation should have a careful evaluation of suicide risk. [A]

B-11. Is Patient in Full Remission?

Action Statement

Patients with bipolar depression who have been without any significant symptoms of depression for two months should be considered to be in full remission.

Recommendations

  1. Following remission of the depressive episode, it is appropriate to consider withdrawing antidepressant treatment after 4 to 6 months. [C]

B-12. Assess Adherence, Side Effects, and Psychosocial Barriers to Therapy; Assess Risk for Suicide

Action Statement

Assess adherence to treatment, and other possible causes for partial response or no-response.

Recommendations

  1. Patients should be followed by a scheduled visit to the clinic periodically, depending on their response, for a thorough assessment that includes:
    1. Adherence to therapy. Reasons for noncompliance should be explored with the patient. [B]
    2. Assessment of potential adverse effects. [A] (See Table E - 1 "Adverse Events – Lithium"; Table E - 4 "Adverse Events Antiepileptic Medications"; and Table E - 6 "Adverse Events - Antipsychotics," in the original guideline document).
    3. Monitoring of serum concentration for lithium and other appropriate blood work to maintain efficacy and avoid toxicity (See Table E - 5 "Recommended Pharmacotherapy Monitoring," in the original guideline document).
    4. For antipsychotics monitor weight, waist circumference, blood pressure, BMI, plasma glucose and fasting lipids [C]. (See Table E - 8 "Monitoring Parameters and Frequency for Metabolic Adverse Effects Secondary to Second Generation Antipsychotics," in the original guideline document).
    5. Assess for co-occurring medical conditions that can mimic or exacerbate BD depression. [B]
    6. Assessment of any changes in patient's family and community support (housing, care givers, employment, income, social networks). [B]
  1. Assess for improvement or change of the core symptoms of depression through a clinical interview or the use of a standardized rating scale to determine changes in the severity of depression. [I]
  2. Patients with suicidal ideation should have a careful evaluation of suicide risk. [A]

B-13. Consider ECT or Alternative Therapies; Monitor for Risk for Mood Destabilization

Action Statement

ECT should be utilized for the treatment of severe and refractory bipolar depression in patients who consent and have no absolute medical contraindications.

Recommendations

  1. ECT should be initiated in patients with severe or refractory bipolar depression who consent and have no absolute medical contraindications. [B]
  2. The risk for mood destabilization or switching to mania should be evaluated and the patient should be monitored closely for emergent symptoms.

Module C: Maintenance/Prophylaxis Phase

C-1. Adult Person with BD in Symptomatic Remission after an Acute Manic/Hypomanic/Mixed or Depressive Episode

Recommendations

  1. A structured approach to maintenance management of the patient with BD who has recently experienced an acute episode and is now in remission is recommended. [A]
  2. Patients who have had an acute manic episode should be treated for at least 6 months after the initial episode is controlled and encouraged to continue on life-long prophylactic treatment with medication. [A]
  3. Risks and benefits of long term pharmacotherapy should be discussed prior to starting medication and should be a continued discussion item during treatment. [C]
  4. Patients who have had more than one manic episode or with one manic and one depressive episode, or three or more depressive episodes, should be encouraged to continue on life-long prophylactic treatment, as the benefits clearly outweigh the risks. [A]
  5. If medications are to be discontinued, they should be slowly and gradually tapered over at least a 2 to 4 week period, unless medically contraindicated, in order to prevent an episode of BD and/or increase the risk of suicide. [B]

C-2. Assess Course of Illness, Treatment History, and Current Clinical Status

Action Statement

Patients with BD who have achieved remission from an acute episode require a thorough evaluation to determine appropriate maintenance treatment.

Recommendations

  1. A complete clinical assessment should be obtained for patients with BD who are entering the maintenance phase following an acute episode, to include:
    1. Clinical status
    2. Medical comorbidities
    3. Psychiatric comorbidities
    4. Psychosocial status
    5. Current medications
    6. Past medications
    7. Medication compliance
    8. Suicide risk
    9. Substance use

C-3. Is Patient Receiving Tolerable and Clinically Effective Medications for Maintaining Remission?

Patients who are clinically stable and tolerating their medication can be maintained on the agent used in acute treatment.

Patients who continue to experience sub-threshold symptoms or breakthrough mood episodes may require the addition of another maintenance medication. Certain medications have shown stronger evidence for the prevention of mania or depression. (See Annotation C-4)

C-4. Institute Maintenance Medications That Have Demonstrated Clinical Efficacy for at Least 6 Months

Action Statement

Pharmacotherapy should optimally consist of a clinically effective medication for the prevention of manic and depressive episodes and should be prescribed to patients with BD in the maintenance phase.

Recommendations

  1. Consider using the agent(s) that have been effective in the recent acute phase or in past mood episodes. (See Table C-2 in the original guideline document) [I]
  2. Consider reducing to a single medication (monotherapy) that has been shown to be most effective in delaying/preventing relapse while minimizing the potential risks by monitoring the patient closely. [I]
  3. Consider the pharmacokinetics, adverse effects, and drug-drug interactions when selecting the specific agent(s). [I]
  4. Lithium [A] or olanzapine [B] should be considered as first-line maintenance treatment for adults with BD to delay/prevent the recurrence of mania.
  5. Risperidone long-acting intramuscular (IM) injection should be considered for patient with frequent relapses. [B]
  6. Aripiprazole [B] may be considered as a second line treatment to prevent or delay the recurrence of mania.
  7. Lithium, or lamotrigine, should be considered as a first-line treatment to prevent or delay the recurrence of bipolar depression. [B]
  8. Olanzapine may be considered as a second line treatment to prevent/delay bipolar depressive episodes. [C]
  9. Quetiapine augmentation of valproate or lithium should be considered a first-line maintenance treatment for adults with BP to maintain remission and prevent new episodes of all types. [B]
  10. Adding olanzapine to lithium or valproate may be used in maintenance treatment to delay or prevent symptomatic relapse. [C]
  11. In patients with a history of severe or recent mania, lamotrigine should be used in combination with lithium, olanzapine, or aripiprazole. [I]
  12. Valproate and carbamazepine may also be considered as alternatives for maintenance medication. [C]
  13. There is insufficient evidence to recommend for or against other antipsychotic or anti-epileptic agents in the maintenance treatment of BD.

C-5. Assess for Adverse Events within 2 Weeks

Action Statement

Assess for adverse effects and tolerability after any change of treatment strategy.

Recommendations

  1. Using a standardized clinical tool in addition to a clinical interview, assess for response to treatment, adherence to treatment and adverse effects of treatment after initiating or changing treatment.
  2. Identified side effects should be managed to minimize or alleviate if possible.

See Table E - 1 "Adverse Events – Lithium"; Table E - 4 "Adverse Events Antiepileptic Medications"; and Table E - 6 "Adverse Events - Antipsychotics," in the original guideline document.

C-6. Provide Psychoeducation, Psychotherapy, and Family Intervention as Indicated

Recommendations

  1. Providers should give simple educational messages regarding medication therapy (e.g., take daily, understand gradual nature of benefits, continue even when feeling better, do not stop without checking with the provider, and specific instructions on how to address issues or concerns) in order to increase adherence to treatment. [C]
  2. Consider psychoeducation and care management for patients with BD. [B] For best effect consider offering in a structured group setting with ongoing care/disease management [A]
  3. Patients on prophylactic medications, who are recovering or have recovered from a manic or hypomanic episode, as well as those currently in a depressive episode and who are at high risk for non-adherence to medication; should be considered for one of the following evidence-based psychotherapeutic interventions:
    1. Cognitive behavioral therapy (CBT) [A]
    2. Family therapy [B]
    3. Interpersonal and Social Rhythm Therapy (IPSRT) [B]

C-7. Assess Response after 1-3 months; Monitor All Medications and Manage Adverse Effects. Monitor and Encourage Adherence. Discuss with Patient Risks and Benefits of Long-Term Pharmacotherapy

Action Statement

Patients' adherence to treatment should be assessed. Barriers to adherence should be addressed.

Recommendations

  1. Patients whose BD is in remission should be followed by a scheduled visit to the clinic every 1 to 3 months with a thorough assessment of current and recent symptoms. [I]
  2. All patients on medication should be monitored for potential adverse effects. [B] (See Module E: Table E - 1 "Adverse Events – Lithium"; Table E - 4 "Adverse Events Antiepileptic Medications"; and Table E - 6 "Adverse Events - Antipsychotics," in the original guideline document).
  3. Monitor serum concentration for lithium, carbamazepine, or valproate and other appropriate blood work every 3 to 6 months to maintain efficacy and avoid toxicity. [A/B] (see Table E - 5 "Recommended Pharmacotherapy Monitoring," in the original guideline document)
  4. For antipsychotics monitor weight (BMI), waist circumference, blood pressure, plasma glucose and fasting lipids annually [C]. (See Table E - 8 "Monitoring Parameters and Frequency for Metabolic Adverse Effects Secondary to Second Generation Antipsychotics," in the original guideline document)
  5. Adherence to medication therapy should be routinely evaluated at each visit. Reasons for noncompliance should be explored with the patient. [A]
  6. Assess any changes in patient's family and community support (e.g., housing, care givers, employment, income, social networks). [C]

C-8. Is There Any Medical or Psychiatric Comorbidity?

Action Statement

Identify any medical or psychiatric comorbidity in patients receiving maintenance treatment for BD.

Recommendations

  1. Manage co-occurring substance use disorders, including nicotine disorders in patients with BD using the VA/DoD guidelines for substance use disorders and for tobacco use while continuing to manage the BD according to this guideline. Addiction focused treatment should be coordinated with the treatment of BD. [I]
  2. Refer patients with other co-occurring major psychiatric illnesses to specialty care. [I]
  3. Refer patients who have had significant suicidality or homicidality to specialty care. [I]
  4. Because of possibility of adverse drug-drug interactions, the provider should consider all current medications including over-the-counter (OTC) medication and nutritional supplements whenever new medications are prescribed.
  5. In selecting a drug treatment regimen for patients with BD, clinicians should be aware of the patient’s other psychiatric and medical conditions and should try to avoid exacerbating them.
  6. In selecting a drug treatment regimen for patients with diabetes or obesity consider the risk and benefit of utilizing medications that are less associated with weight gain.
  7. Primary care providers should continue to follow patients who are referred to specialty care, and should coordinate the management of all of their health conditions.

C-9. Is Patient in Recurrence and Meets DSM-IV-TR Criteria for Bipolar Episode?

Action Statement

For patients who experience a recurrence, manage their care according to the respective module.

Recommendations

See Module A - for management of Bipolar Acute Manic/Hypomania/Mixed episode.

See Module B - for management of Bipolar Acute Depressive Episode.

C-10. Optimize Medication Regimen and Psychotherapy Interventions

Recommendations

  1. If patient is having intolerable side effects switch to another effective treatment. [I]
  2. If symptoms of mania, hypomania, or depression re-occur but do not meet criteria for a relapse adjust current treatment as follows:
    • Assess compliance and if medications are in therapeutic range [I]
    • Assess for other factors that may cause the symptoms (i.e., medical condition or substance use) [I]
    • If medication is not in therapeutic range adjust medication to maximum range [I]
    • Consider adding one of the evidence based psychotherapeutic interventions [B] (See Module D - Psychosocial Interventions)
    • Consider adding an augmenting agent (quetiapine or olanzapine) [A]
    • Consider switching to another treatment that is effective for maintenance treatment. [I]
  1. Risks and benefits of long-term pharmacotherapy should be discussed prior to starting medication and during treatment. [A]

C-11. Consider Discontinuing Medications That Are Not Critical for Mood Stabilization while Maintaining Symptomatic and Functional Remission. Continue Follow-Up to Prevent Recurrence and Promote Recovery and Rehabilitation

Recommendations

  1. Medications that are believed not to be critical for mood stabilization are recommended to be gradually tapered one at a time.
  2. In all of these cases the taper should be done gradually with close observation by the provider, patient, and if possible, other objective sources of information (e.g., spouses).
  3. If symptoms re-occur, alternative medications with lower side effects burden or using somewhat lower doses should be considered.

Module D: Psychosocial Interventions

Psychoeducation

Recommendations

  1. Patient should receive psychoeducation that emphasizes: [B]
    1. The importance of active involvement in their treatment
    2. The nature and course of their bipolar illness
    3. The potential benefit and adverse effects of treatment options
    4. The recognition of early signs of relapse
    5. Behavioral interventions that can lessen the likelihood of relapse including careful attention to sleep regulation and avoidance of substance misuse
  1. With the patient's permission, family members or significant other should be involved in the psychoeducation process. [C]
  2. A structured group format in providing psychoeducation and care management for patients with clinically significant mood symptoms should be considered. [A]

Psychotherapy Strategies

Cognitive Behavioral (CBT)

Recommendations

  1. Cognitive behavioral treatment may be considered as an adjunct to pharmacotherapy for patients with BD who have achieved remission from an acute manic episode and who have had fewer than 12 previous BD acute episodes [A]
  2. Implementation of CBT should include components of:
    1. Education regarding symptoms, course and treatment of BD
    2. Scheduling of pleasurable events to alleviate inactivity
    3. Teaching the skill of cognitive re-structuring
    4. Learning to identify maladaptive thoughts and challenge them on logical grounds
    5. Learning to replace maladaptive thoughts with balanced or adaptive thinking
    6. Problem solving
    7. Learning to detect the earliest signs of recurrence and implement early intervention plans.
  1. In considering patients for CBT it is recommended that careful screening for hypomanic episodes be conducted (dynamism, persuasiveness, productiveness) as there is some evidence to support that CBT is less effective with these patients.
  2. CBT can be considered as an approach to reduce and prevent depressive symptoms in BD rather than manic symptoms as it has been found to be most effective in depression. [B]

Interpersonal and Social Rhythm Therapy (IPSRT)

Recommendations

  1. Interpersonal and social rhythm therapy (IPSRT) may be considered for patients with BD who have achieved remission from an acute manic episode and are maintained on prophylactic medication. [B]
  2. IPSRT should contain the following components:
    1. Patients should complete the Social Rhythm Metric questionnaire which is a self-report instrument for tracking and quantifying daily and nightly routines, along with ratings of mood.
    2. Providers need to assist patients in keeping regular routines (e.g., bed times, wake times, exercise) and minimizing the impact of events that could disrupt their moods and daily/nightly stability.
    3. Providers need to maintain an interpersonal focus that concerns the resolution of the patient’s current problems (e.g., how to communicate better with one’s spouse) and developing strategies for preventing the same problems from recurring in the future.

Family Therapy

Recommendations

  1. Couples and families who are coping with BD should be considered for family therapy either on an inpatient or outpatient basis. [C]
  2. Family focused therapy should contain the following four components:
    1. Initial assessment
    2. Psychoeducation about the nature, course, and treatment of BD, including the importance of medication consistency, identifying early warning signs of relapse, and implementing relapse prevention strategies
    3. Communication and enhancement skills, notably role playing and rehearsal of tools for active listening and expressing positive or negative feelings
    4. Problem solving skills

Chronic Care Models Interventions

Recommendations

  1. Patients, who have BD, should be offered chronic care model-based interventions [B], especially when patients are more symptomatic, or were recently hospitalized. [A]

Module E: Pharmacotherapy Interventions

Refer to the original guideline document for detailed information about medications used to treat BD, including lithium, antiepileptics, antipsychotics, and antidepressants.

Electroconvulsive Therapy (ECT)

Recommendations

  1. ECT may be considered for manic patients who are severely ill and/or whose mania is treatment resistant, those patients who express a preference for ECT and patients with severe mania during pregnancy. [C]
  2. ECT should be used only to achieve rapid and short-term improvement of severe symptoms after an adequate trial of other treatment options has proven ineffective and/or when the condition is considered to be potentially life-threatening.
  3. ECT for BD is indicated as the primary therapy in the following [A]:
    1. Psychotic symptoms
    2. Catatonia
    3. Severe suicidality
    4. Food refusal leading to nutritional compromise
    5. History of prior positive response to ECT
  1. ECT is considered as first line therapy for the following conditions [B]:
    1. Need for rapid, definitive treatment response on either medical or psychiatric grounds
    2. Risks of other treatments outweigh the risks of ECT
    3. Adequate trial of other treatment options (including drugs) has proven ineffective
    4. Patient preference
  1. ECT may be considered as augmented therapy in the following [B]:
    1. Treatment failure
    2. Unavoidable adverse effects using alternative treatments
    3. Deterioration of patient's condition such that the first criterion is met

Module F: Bipolar Disorder in Older Adults

Action Statement

Older adults with BD who are receiving psychopharmacological treatments should be monitored closely for evidence of efficacy, side effects, toxicity, and interactions with other medications. They should also be considered for evidence-based psychotherapeutic interventions and caregiver supports.

Recommendations

  1. The likelihood of possible benefits with all medications used to treat BD in older adults needs to be balanced against potential risks.
  2. Polypharmacy in older adults should be avoided.
  3. Lithium can be used in older adults to treat acute mania, as maintenance, and also to treat bipolar depression.
  4. Overall, valproate appears to be better tolerated than lithium in older adult patients with BD.
  5. Carbamazepine is an alternative treatment to lithium for older patients with severe cardiovascular or renal disease.
  6. Generally, benzodiazepines should be used with caution. However, they may be needed to treat extreme agitation. Care should be taken in the presence of comorbid medical conditions or possible drug-drug interactions. Older adults may be more sensitive than younger adults to central effects of benzodiazepines leading to ataxia, confusion, disinhibition, and delirium. If needed, a shorter-acting benzodiazepine which is metabolized by conjugation could be used, e.g., lorazepam.
  7. The role of antidepressants in the management of BD is complex and sometimes controversial. Older adults are more likely than younger adults to develop initial manic episodes during antidepressant therapy. The provider should use tricyclics with caution in the older populations as these have been shown to cause an increased risk of treatment-emergent affective switches in this age group. It has been reported that the first line treatments for bipolar depression are mood stabilizers, and that adjunctive antidepressants should be used with caution. However, older adults with BD treated with a mood stabilizer and an antidepressant may be less likely to attempt suicide.
  8. The treatment of secondary mania in older adults is relatively similar to the treatment of primary mania and typically does not usually require prophylaxis unlike primary mania. However, there may be increased sensitivity to side effects of medications, so dosages should be modified. Mania associated with structural central nervous system disease may respond better to carbamazepine or valproate. Newer anticonvulsant agents, such as topiramate and lamotrigine, have not been specifically studied yet in this patient population.
  9. The preferred treatment for older adults with acute mania is an atypical antipsychotic (e.g., risperidone, quetiapine, olanzapine, and aripiprazole) combined with a mood stabilizer. Comorbid medical conditions such as diabetes, constipation, hypotension, weight may influence medication choice.
  10. The provider needs to consider that mood stabilizers may impact cognitive functioning in older adults. Adverse effects were reported to be least likely in those taking lamotrigine or oxcarbazepine, intermediate with lithium, and greatest with valproate, carbamazepine, and topiramate. In a study of older adults with BD, lithium was no more likely to impair cognition than other therapies, but this study was limited by low statistical power.
  11. There is growing concern regarding metabolic issues related to second-generation antipsychotics. The risk is greatest with clozapine and olanzapine, followed by quetiapine and risperidone, and then followed by aripiprazole and ziprasidone. If an older individual is to be maintained on a second-generation antipsychotic, baseline measures of weight, waist circumference, fasting blood glucose, and glycosylated hemoglobin (HbA1c) should be obtained. Weight or waist circumference can be monitored every two months and fasting blood glucose checked every six months or sooner if there is significant weight gain.
  12. All pharmacological interventions for older adults with BD should be combined with cognitive, behavioral, family, interpersonal and social rhythm therapies in conjunction with psychoeducation and chronic disease management.

Adverse Effects of Medications

  • Lithium: See Table E - 1, "Adverse Events—Lithium," in the original guideline document.
  • Antiepileptics: See Table E - 4, "Adverse Events—Antiepileptic Medications," in the original guideline document.
  • The provider needs to consider that mood stabilizers may impact cognitive functioning in older adults. Adverse effects were reported to be least likely in those taking lamotrigine or oxcarbazepine, intermediate with lithium, and greatest with valproate, carbamazepine, and topiramate.
  • Antipsychotics: neuroleptic malignant syndrome (NMS)
    • See Table E - 6, "Adverse Events—Antipsychotics," in the original guideline document.
    • There is growing concern regarding metabolic issues related to second-generation antipsychotics in older adults. The risk is greatest with clozapine and olanzapine, followed by quetiapine and risperidone, and then followed by aripiprazole and ziprasidone. If an older individual is to be maintained on a second-generation antipsychotic, baseline measures of weight, waist circumference, fasting blood glucose, and glycosylated hemoglobin (HbA1c) should be obtained.
  • Antidepressants:
    • See Table E - 9, "Adverse Events—Antidepressants," in the original guideline document.
    • Older adults are more likely than younger adults to develop initial manic episodes during antidepressant therapy. The provider should use tricyclics with caution in the older populations as these have been shown to cause an increased risk of treatment-emergent affective switches in this age group.

Electroconvulsive Therapy (ECT)

ECT may cause adverse cognitive effects. Pertinent preexisting medical conditions that put patients at higher risk of complications include hypertension, coronary artery disease, congestive heart failure, aortic stenosis, implanted cardiac devices, atrial fibrillation, obstructive lung disease, and asthma.

Contraindications

Lithium is to be avoided in the first trimester of pregnancy due to the risk of fetal Ebstein's anomaly with a risk that is 10 to 20 times greater than the general population. Lithium is contraindicated during breastfeeding due to concerns of infant lithium toxicity.


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Self-Help Resources For Depression

Self-Help Bipolar Resources

Improving Positive Behavior

Philosophers for the past 2,500 years have taught that it is very beneficial to start the day with goal-setting, and end the day with a brief review.

This habit of planning the day in the morning, then assessing these plans in the evening has been shown to increase health and happiness. There is an additional benefit from doing a weekly review of your life satisfaction.

Note: When each of the following videos finishes; you must exit YouTube (by manually closing the window) in order to return to this webpage.



International Space Station (For Meditation)



Planning My Day (5-Minute Meditation Video)

Planning My Day (Picture)



Reviewing My Day Or Week (5-Minute Meditation Video)



Life Satisfaction Scale (Video)



Healthy Social Behaviors Scale (Video)



Mental Health Scale (Video)

Why We All Need to Practice Emotional First Aid



The Philosophy Of Stoicism (5 minute video)

Stoicism 101 (52 minute video)



The Roman emperor and Stoic philosopher Marcus Aurelius ruled from 161 to 180 A.D.

An Example Of Mindfulness Meditation (10 minute video)

In the 5th century BCE, Buddha spent 6 years of his life mastering mindfulness meditation. He then decided to look beyond meditation. Buddha concluded that simply emptying the mind of thought is calming, but otherwise it accomplishes little - since "You return to the same world". Instead, Buddha taught that we should change our world by seeking enlightenment through practicing compassion, and living a calm, peaceful, happy life.



7-Minute Workout Is All You Need To Get Back Into Physical Shape


Click Here For More Self-Help



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  • The best summary on bad research is given by Laura Arnold in this Tedx lecture. If you read nothing else about research, you owe it to yourself to watch this short video - it is excellent!

  • Criteria For High Quality Research Studies

  • It is imperative that medical researchers conduct high quality research studies, otherwise the US Food and Drug Administration (FDA) refuses to licence their new drug or therapy. In 2009, the cost of successfully licensing one new drug or therapy under the FDA scheme was estimated to be US$1,000 million. Thus psychiatric research which leads to FDA approval of a new drug or therapy has to be of the highest quality; however the majority of psychological research studies on new therapies fail to reach these high standards for research. This could explain why two-thirds of psychological research studies can't be replicated. High quality research must meet the following criteria:

    • Randomized Controlled Trial:
      Ask: Was the trial randomized? Was the randomization procedure described and was it appropriate? The best research design is to have research subjects randomly assigned to an experimental or control group. It is essential that confounding factors be controlled for by having a control group or comparator condition (no intervention, placebo, care as usual etc.).

    • Representative Sample:
      Ask: Do the research subjects represent a normal cross-section of the population being studied? Many psychological research studies using university students are flawed because their subjects are not representative of the normal population since they are all W.E.I.R.D. (White, Educated, Intelligent, Rich, and living in a Democracy).

    • Single Blind Trial:
      Ask: Was the treatment allocation concealed? It is essential that the research subjects are kept "blind" as to whether they are in the experimental or control group (in order to control for any placebo effects).

    • Double Blind Trial (Better Than Single Blind Trial):
      Ask: Were blind outcome assessments conducted? In a double blind study, neither the research subjects nor the outcome assessors know if the research subject is in the experimental or control group. This controls for both the placebo effect and assessor bias.

    • Baseline Comparability:
      Ask: Were groups similar at baseline on prognostic indicators? The experimental and control groups must be shown to be comparable at the beginning of the study.

    • Confounding Factors:
      Ask: Were there factors, that weren't controlled for, that could have seriously distorted the study's results? For example, research studies on the effectiveness of mindfulness cognitive therapy in preventing depressive relapse forgot to control for whether the research subjects were also simultaneously receiving antidepressant medication or other psychological treatments for depression.

    • Intervention Integrity:
      Ask: Was the research study protocal strictly followed? The research subjects must be shown to be compliant (e.g., taking their pills, attending therapy) and the therapists must be shown to be reliably delivering the intervention (e.g., staying on the research protocol).

    • Statistical analysis:
      Ask: Was a statistical power calculation described? The study should discuss its statistical power analysis; that is whether the study size is large enough to statistically detect a difference between the experimental and control group (should it occur) and usually this requires at least 50 research subjects in the study.

      Ask: Are the results both statistically significant and clinically significant? The results should be both statistically significant (with a p-value <0.05) and clinically significant using some measure of Effect Size such as Standardized Mean Difference (e.g., Cohen's d >= 0.33). The summary statistics should report what percentage of the total variance of the dependent variable (e.g., outcome) can be explained by the independent variable (e.g., intervention). In clinical studies, the study should report the number needed to treat for an additional beneficial outcome (NNTB), and the number needed to treat for an additional harmful outcome (NNTH).

        Number Needed To Benefit (NNTB): This is defined as the number of patients that need to be treated for one of them to benefit compared with a control in a clinical trial. (It is defined as the inverse of the absolute risk reduction.) Note: Statistically, the NNTB depends on which control group is used for comparison - e.g., active treatment vs. placebo treatment, or active treatment vs. no treatment.

        Number Needed To Harm (NNTH): This is defined as the number of patients that need to be treated for one of them to be harmed compared with a control in a clinical trial. (It is defined as the inverse of the absolute increase in risk of harm.)

        Tomlinson found “an NNTB of 5 or less was probably associated with a meaningful health benefit,” while “an NNTB of 15 or more was quite certain to be associated with at most a small net health benefit.”

      Ask: Does the researcher accept full responsibility for the study's statistical analysis? The researcher should not just hand over the study's raw data to a corporation (that may have $1,000 million invested in the study) to do the statistical analysis.

    • Completeness of follow-up data:
      Ask: Was the number of withdrawals or dropouts in each group mentioned, and were reasons given for these withdrawals or dropouts? Less than 20% of the research subjects should drop out of the study. The intervention effect should persist over an adequate length of time.

    • Handling of missing data:
      Ask: Was the statistical analysis conducted on the intention-to-treat sample? There must be use of intention-to-treat analysis (as opposed to a completers-only analysis). In this way, all of the research subjects that started the study are included in the final statistical analysis. A completers-only analysis would disregard those research subjects that dropped out.

    • Replication of Findings:
      Ask: Can other researchers replicate this study's results? The research study's methodology should be clearly described so that the study can be easily replicated. The researcher's raw data should be available to other researchers to review (in order to detect errors or fraud).

    • Fraud:
      Ask: Is there a suspicion of fraud? In a research study, examine the independent and dependent variables that are always measured as a positive whole number (e.g., a variable measured on a 5-point Likert-type scale ranging from "1 = definitely false to 5 = definitely true" etc.). For each of these variables, look at their sample size (n), mean (M) and standard deviation (SD) before they undergo statistical analysis. There is a high suspicion of fraud in a study's statistics:

      • If the M is mathematically impossible (online calculator): This is one of the easiest ways to mathematically detect fraud. The mean (M) is defined as "the sum (Sum) of the values of each observation divided by the total number (n) of observations". So: M = Sum/n. Thus: (Sum) = (M) multiplied by (n). We know that, if a variable is always measured as a positive whole number, the sum of these observations always has to be a whole number. For these variables to test for fraud: calculate (M) multiplied by (n). This calculates the Sum which MUST be a positive whole number. If the calculated Sum isn't a positive whole number; the reported mean (M) is mathematically impossible - thus the researcher either cooked the data or made a mistake. A recent study of 260 research papers published in highly reputable psychological journals found that 1 in 2 of these research papers reported at least one impossible value, and 1 in 5 of these research papers reported multiple impossible values. When the authors of the 21 worst offending research papers were asked for their raw data (so that its reliability could be checked) - 57% angrily refused. Yet such release of raw data to other researchers is required by most scientific journals. (Here is an example of a research paper filled with mathematically impossible means.)

      • If the SD is mathematically impossible (online calculator): When researchers fraudulently "cook" their data, they may accidently give their data a mean and standard deviation that is mathematically impossible for a (normally distributed) strictly positive variable (because the "cooked" M and SD would mathematically require the strictly positive variable's range of data to include negative numbers). For a normally distributed sample of size of 25-70, this occurs when the SD is greater than one-half of the M; for a sample size of 70+, this occurs when the SD is greater than one-third of the M [using these formulas].

      • If the SD/M is very small (i.e., the variable's standard deviation is very small compared to the mean suggesting data smoothing).

      • If the SD's are almost identical (i.e., the variables have different means but almost identical standard deviations).

      • If the 4th digit of the values of the variables aren't uniformly distributed - since each should occur 10% of the time (Benford's Law).

      • If the researcher is legally prevented from publishing negative findings about a drug or therapy because that would violate the "nondisclosure of trade secrets" clause in the research contract (i.e., it is a "trade secret" that the drug or therapy is ineffective - hence this can not be "disclosed"). Approximately half of all registered clinical trials fail to publish their results.

      • If the researcher refuses to release his raw data to fellow researchers (so that they can check its validity). In order to be published in most scientific journals, a researcher must promise to share his raw data with fellow researchers. Thus a researcher's refusal to do so is almost a sure indicator of fraud.

      • If the research study's data contradicts the study's own conclusions - surprisingly, this often occurs.

  • Calling Bullshit In The Age of Big Data - "Bullshit is language, statistical figures, data graphics, and other forms of presentation intended to persuade by impressing and overwhelming a reader or listener, with a blatant disregard for truth and logical coherence." Reading the syllabus of this university course should be required reading for every student of mental health. This syllabus is absolutely fantastic!

  • Statistical Methods in Psychology Journals: Guidelines and Explanations - American Psychologist 1999

  • Not All Scientific Studies Are Created Equal - video

  • The efficacy of psychological, educational, and behavioral treatment

  • Estimating the reproducibility of psychological science

  • Psychologists grapple with validity of research

  • Industry sponsorship and research outcome (Review) - Cochrane Library

  • 'We've been deceived': Many clinical trial results are never published - (text and video)

  • Junk science misleading doctors and researchers

  • Junk science under spotlight after controversial firm buys Canadian journals

  • Medicine with a side of mysticism: Top hospitals promote unproven therapies - Are some doctors becoming modern witchdoctors?

  • When Evidence Says No, But Doctors Say Yes


  • Major pharmaceutical company fined $3 billion US for making false claims - (text and video) [Editor: This is an example of how a major pharmaceutical company purposely produced fraudulant research in order to increase its sales.] In 2001, GlaxoSmithKline, the manufacturer of the antidepressant Paxil, published research that falsely claimed that Paxil was effective in the treatment of adolescent depression. This claim and others were found to be fraudulant, and in 2012 GlaxoSmithKline was fined $3 billion US in court settlements. Subsequent independent reanalysis of the original Paxil research data clearly proved that the original study was fraudulant. This fraudulant research paper was published in a top psychiatric journal, and has never been retracted or corrected.

  • Cochrane Collaboration - the best evidence-based, standardized reviews available

Research Topics:

Bipolar Disorder - Latest Research (2016-2017)

Cochrane Review (The best evidence-based, standardized reviews available)

Strong evidence of effectiveness:
  • Valproate for acute mood episodes in bipolar disorder (2009) (There is consistent, if limited, evidence that valproate is an efficacious treatment for acute mania. Valproate may be less efficacious than olanzapine.)

  • Lithium for maintenance treatment of mood disorders (2009) (This systematic review indicates that lithium is an efficacious maintenance treatment for bipolar disorder. In unipolar disorder the evidence of efficacy is less robust. Caution should be exercised in abruptly stopping lithium therapy in patients who have been taking it successfully for some time, due to the high risk of relapse. This review does not cover the relative efficacy of lithium compared with other maintenance treatments, which is at present unclear. There is no definitive evidence from this review as to whether or not lithium has an anti-suicidal effect. Systematic reviews and large scale randomised studies comparing lithium with other maintenance treatments (e.g. anti-convulsants, antidepressants) are necessary. Outcomes relating to death and suicidal behavior should be included in all future maintenance studies of mood disorder.)

Some evidence of effectiveness:
  • Compulsory community and involuntary outpatient treatment for people with severe mental disorders (2014) (Compulsory community treatment (CCT) for people with severe mental health problems is used in many countries. Supporters of this approach suggest that it is less restrictive and better to compulsorily treat someone in the community than to subject them to repeated hospital admissions. They also argue that it is effective in bringing stability to the lives of people with severe mental illness. Opponents of CCT fear treatment and support will be replaced by a greater emphasis on control, restraint, and threat. CCT may also undermine the relationship between healthcare professionals and patients, leading to feelings of mistrust and being controlled, which may drive people with severe mental illnesses away from services. Given the widespread use of such powers, which effectively force people in the community to compulsorily undergo treatment, it is important to assess the benefits, effectiveness or possible hazards of compulsory treatment. CCT results in no significant difference in service use, social functioning or quality of life compared with standard voluntary care. People receiving CCT were, however, less likely to be victims of violent or non-violent crime. Short periods of conditional leave may be as effective (or non-effective) as formal compulsory treatment in the community. Evaluation of a wide range of outcomes should be considered when this legislation is introduced. However, conclusions are based on three relatively small trials, with high or unclear risk of blinding bias, and evidence we rated as low to medium quality.)

  • Valproate for keeping people with bipolar disorder well, after mood episodes (2013) (Limited evidence supports the efficacy of valproate in the long-term treatment of bipolar disorder.)

  • Omega-3 fatty acids for bipolar disorder (2009) (Results from one study showed positive effects of omega-3 as an adjunctive treatment for depressive but not manic symptoms in bipolar disorder. These findings must be regarded with caution owing to the limited data available. )

  • Olanzapine in long-term treatment for bipolar disorder (2009) (Though based on a limited amount of information, there is evidence that olanzapine may prevent further mood episodes in patients who have responded to olanzapine during an index manic or mixed episode and who have not previously had a satisfactory response to lithium or valproate. However, notwithstanding these positive results, the current evidence is stronger for lithium as first line maintenance treatment of bipolar disorder.)

  • Interventions for helping people recognise early signs of recurrence in bipolar disorder (2009) (Early warning signs (EWS) interventions, targeted at improving the recognition and self-management of manic and depressive symptoms, are intended to train people with recurrent bipolar affective disorder to recognise early warning signs of recurrence and to avert adverse outcomes. This review demonstrated that these interventions, in addition to treatment as usual (TAU), including medication and regular appointments with health professionals, have benefits on time to recurrence and hospitalisation. Compared with TAU only, EWS interventions also resulted in improved functioning at eighteen months, although these data were sparse and the findings should be interpreted with caution. EWS interventions did not appear to have any effect on depressive or manic symptoms, although again, these findings were based on small numbers of potentially selected patients in remission. It should be noted that EWS was used along with other psychological interventions, and it is not entirely clear what proportion of the beneficial effect was due to the EWS intervention alone.)

No evidence of effectiveness:
  • Family interventions for bipolar disorder (2009) (To date there is only a small and heterogeneous body of evidence on the effectiveness of family oriented approaches for bipolar disorder. Whilst results from individual studies did not suggest a significant effect for family interventions when added to drug therapy, the studies provide insufficient evidence to draw conclusions which can be generalised to everyday practice. Further research using appropriate randomised controlled trial methodology and evaluating family interventions other than psychoeducation is called for in this under-researched and important topic.)

Not yet possible to draw any definite conclusions due to insufficient evidence:
  • Tiagabine in the maintenance treatment of bipolar disorder (2012) (There is an insufficient methodologically rigorous evidence base to draw any conclusions regarding the use of tiagabine in the maintenance treatment of bipolar disorder. There have been some reports of syncope or seizures, or both, when tiagabine has been used for the acute treatment of mania. It needs to be established if such adverse effects occur in the maintenance phase as well.)

  • Tiagabine to treat acute affective episodes in bipolar disorder (2012) (We found no randomised controlled trials of tiagabine in the treatment of acute episodes of bipolar disorder. However, there are reports that a number of patients suffered episodes of syncope or seizure. Further investigation of the efficacy and acceptability of tiagabine in the treatment of acute affective episodes of bipolar disorder should await the clarification of the nature of the reported episodes of syncope and seizure-like activity and an examination of the level of risk involved.)

  • Oxcarbazepine for acute affective episodes of bipolar disorder (2011) (Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states. From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission.)

  • Oxcarbazepine in the maintenance treatment of bipolar disorder (2009) (There is an insufficient methodologically rigorous evidence base to provide guidance on the use of oxcarbazepine in the maintenance treatment of bipolar disorder. )

  • Topiramate for acute affective episodes in bipolar disorder (2009) (There is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness, either in monotherapy or as an adjunctive treatment.)

  • Risperidone in the long-term treatment for bipolar disorder (2009) (No studies involving risperidone were identified which randomly assigned treatment for long-term relapse prevention. Trials involving random assignment of risperidone and other treatments for long-term treatment are needed.)


Note: The Cochrane Reviews are the best in psychiatry, but they do not cover all psychiatric topics. Thus it is essential that you also read the following Research Review Articles.

Review Articles On The Effectiveness Of Therapy

  • 2014 Research Review Articles

    • Biological Factors

      • Gender differences in thyroid system function: relevance to bipolar disorder and its treatment. (The prevalence of thyroid disease was found to be much higher in females than males, and to increase with age. The most commonly detected abnormality was subclinical hypothyroidism, which was found to occur in up to 20% of postmenopausal women. Females also had higher rates of thyroid autoimmunity. Individuals at risk for thyroid disease, such as adult females, may have had less ability to compensate for additional challenges to thyroid metabolism, including lithium treatment. Thyroid abnormalities were associated with a poorer response to standard treatments for mood disorders. Females with treatment-resistant mood disorders may have responded better than males to adjunctive therapy with thyroid hormones. Lithium may impair vital thyroid metabolic pathways secondary to its anti-thyroid activity.)

      • The effect of lithium on thyroid function in patients with bipolar disorder (Since 1963 lithium treatment has been the best proven long-term pharmacotherapy for bipolar disorder (BD), both in the prevention of depressive and manic episodes, along with the reduction of the suicide risk. Thyroid gland and the hypothalamic-pituitary-thyroid (HPT) axis play a role in the pathophysiology, clinical course and treatment of BD. The influence of lithium on the thyroid gland is one of the key side effects in the long-term therapy with this drug. Lithium is accumulated in the thyroid gland at 3 to 4-fold higher concentrations as compared to its plasma levels. Its administration results in the reduced production with release inhibition of thyroid hormones, altering the immune processes of this gland. The most common thyroid side effects associated with long-term lithium treatment are goiter and hypothyroidism. Hyperthyroidism is a rare complication of lithium therapy. Lithium may also induce an increase in the thyroid autoimmunity, especially if such change had been present before lithium treatment producing structural changes in this gland.)

      • The neurobiology of bipolar disorder: identifying targets for specific agents and synergies for combination treatment. (In summary, the data suggested that bipolar disorder (BD) might be associated with neuronal and glial cellular impairment in specific brain areas, including the prefrontal cortex. From molecular and genetics: (1) alterations in dopaminergic system, through catechol-O-aminotransferase; (2) decreased expression and polymorphism on brain-derived neurotrophic factor; (3) alterations cyclic-AMP responsive element binding; (4) dysregulation of calcium signalling, including genome-wide finding for voltage-dependent calcium channel ?-1 subunit are relevant findings in BD.)

    • Physical Therapies

      • (No research review articles)

    • Pharmaceutical Therapies

      • Options for pharmacological treatment of refractory bipolar depression. (Bipolar disorders of types I and II, even when treated by currently standard options, show a marked excess of depressive morbidity. Treated, type I patients in mid-course or from the onset of illness are ill, overall, 50% of weeks of follow-up, and 75% of that unresolved morbidity is depressive. Currently widely held impressions are that bipolar depression typically is poorly responsive to antidepressants, that treatment-resistant depression (TRD) is characteristic of the disorder, and that risk of mania with antidepressant treatment is very high. However, none of these views is supported consistently by available research. TRD may be more prevalent in bipolar than unipolar mood disorders. The available research supports the view that antidepressants may be effective in bipolar depression provided that currently agitated patients are excluded, that risk of mania with antidepressants is only moderately greater than risk of spontaneous mania, and that bipolar TRD is not necessarily resistant to all treatments.)

      • Aripiprazole: a review of its use in the treatment of manic episodes in adolescents with bipolar I disorder. (Recently in the EU, oral aripiprazole (Abilify) 10 mg once daily for 12 weeks was approved for the treatment of moderate to severe manic episodes in adolescents (aged ?13 years) with bipolar I disorder. Approval was based on a phase 3, 30-week US trial in children and adolescents with bipolar I disorder experiencing manic or mixed episodes. Using trial data together with ancillary analyses, the European Medicines Agency concluded that aripiprazole 10 mg once daily for 12 weeks was effective in reducing symptoms of mania, but because of the high drop-out rate, efficacy over 30 weeks of treatment was not proven. Aripiprazole was generally well tolerated in the phase 3 trial. Ancillary analyses indicated that tolerability was less favourable in younger (10-12 years) than in older (>13 years) subjects, and less favourable with the higher (30 mg/day) than the lower dosage (10 mg/day). The drug is associated with sedation, weight gain and extrapyramidal symptoms (EPS), although the incidence of EPS over 12 weeks was not significantly different between aripiprazole 10 mg/day and placebo.)

      • Clinical assessment of lurasidone benefit and risk in the treatment of bipolar I depression using number needed to treat, number needed to harm, and likelihood to be helped or harmed. (There are only 3 FDA-approved treatments for bipolar depression (quetiapine, olanzapine-fluoxetine combination, and lurasidone). We assessed the efficacy, safety, and tolerability of lurasidone for major depressive episodes associated with bipolar I disorder, using number needed to treat (NNT, for benefits), number needed to harm (NNH, for harms), and likelihood of being helped or harmed (LHH, ratio of NNH to NNT, for trade-offs between benefits vs. harms). Data was collected from two 6-week multicenter, randomized, double-blind, placebo-controlled, flexibly-dosed acute bipolar I depression studies, one using lurasidone monotherapy at 20-60mg/d or 80-120mg/d, and the other using lurasidone 20-120mg/d adjunctive to lithium or valproate. The NNT or NNH was calculated for lurasidone vs. placebo for the following dichotomous outcomes: response (50% or greater reduction from baseline on Montgomery Asberg Depression Rating Scale (MADRS) total score); remission (final MADRS total score 12 or less); discontinuation due to an adverse event (AE); weight gain 7% or more from baseline; incidence of spontaneously reported AEs; and incidence of total cholesterol 240mg/dl or more, low-density lipoprotein cholesterol 160mg/dl or more, fasting triglycerides 200mg/dl or more and glucose 126mg/dl or more post-baseline. NNT vs. placebo for response was 5 for lurasidone monotherapy (both dose ranges) and 7 for adjunctive therapy. NNT vs. placebo for remission for lurasidone monotherapy was 6 for 20-60mg/d and 7 for 80-120mg/d and 7 for adjunctive lurasidone. NNH vs. placebo for discontinuation due to an AE for lurasidone monotherapy was 642 for 20-60mg/d and -181 for 80-120mg/d, and for adjunctive lurasidone was -54 (negative NNH denotes an advantage for lurasidone). Lurasidone was not associated with any clinically meaningful mean weight or metabolic changes compared to placebo; NNH vs. placebo for weight gain >7% was 29 for 20-60mg/d and 5550 for 80-120mg/d and 42 for adjunctive lurasidone. The three most frequently occurring AEs with the largest difference in incidence for lurasidone vs. placebo were nausea, akathisia, and somnolence, with NNH values for lurasidone vs. placebo ranging from 11 (nausea with lurasidone monotherapy 80-120mg/d) to 130 (somnolence with lurasidone monotherapy 20-60mg/d). LHH was substantially and consistently >1 (indicating benefit being more likely than harm) when contrasting response or remission vs. AEs or weight gain. NNT, NNH, and LHH help quantify relative benefits (efficacy) and harms (side effects), thus placing lurasidone findings in research studies into clinical perspective. Lurasidone, compared to other treatments approved for bipolar depression, yielded comparable benefits (all had single-digit NNT vs. placebo for response or remission), and less risk of harm (double-digit or greater NNHs with lurasidone compared to single-digit NNHs for sedation with quetiapine and for 7% or more weight gain with olanzapine-fluoxetine combination), and thus a substantially more favorable LHH (1 or greater) with lurasidone monotherapy and adjunctive therapy, compared to quetiapine and olanzapine-fluoxetine combination.)

      • Is the combination of a mood stabilizer plus an antipsychotic more effective than mono-therapies in long-term treatment of bipolar disorder? A systematic review. (Available mood stabilizers, including lithium, fail to prevent relapses in about 40% of bipolar patients. Purpose of the present paper is to review the available data about the efficacy and tolerability of mood stabilizer plus antipsychotic combined treatments. Almost all papers reported combined treatments were more effective than mood stabilizer mono-therapies, but combined treatments had higher risk for side effects. The antipsychotic that presents more evidence of efficacy in combination with mood stabilizers is quetiapine.)

      • An update on the treatment of mixed bipolar states: what is new in 2013? (Most agents efficacious for mania may also be efficacious for mixed episodes.)

      • Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics. (Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%).)

      • The challenge of treatment in bipolar depression: evidence from clinical guidelines, treatment recommendations and complex treatment situations. (The best evidence for a pharmacological treatment exists for quetiapine. Alternatives with limitations are lamotrigine (also in the combination with lithium), carbamazepine and olanzapine. The effectiveness and recommendation of antidepressants in the treatment of bipolar depression remains controversial. Initially, depressive episodes should been treated with one of the named substances with antidepressant properties. In non-responders, a combination of lithium and lamotrigine, or antidepressants in combination with either lithium, an antiepileptic drug or atypical antipsychotics, may be necessary.)

      • Options for pharmacological treatment of refractory bipolar depression. (Bipolar disorders of types I and II, even when treated by currently standard options, show a marked excess of depressive morbidity. Treated, type I patients in mid-course or from the onset of illness are ill, overall, 50 % of weeks of follow-up, and 75 % of that unresolved morbidity is depressive. Currently widely held impressions are that bipolar depression typically is poorly responsive to antidepressants, that treatment-resistant depression (TRD) is characteristic of the disorder, and that risk of mania with antidepressant treatment is very high. However, none of these views is supported consistently by available research. TRD may be more prevalent in bipolar than unipolar mood disorders. In two controlled trials, ketamine was superior to placebo but it is short-acting and not orally active; pramipexole was weakly superior to placebo in one controlled trial; three other drugs failed to outperform controls. Other pharmacotherapies are inadequately evaluated and nonpharmacological options are virtually untested in bipolar TRD. The available research supports the view that antidepressants may be effective in bipolar depression provided that currently agitated patients are excluded, that risk of mania with antidepressants is only moderately greater than risk of spontaneous mania, and that bipolar TRD is not necessarily resistant to all treatments.)

      • Antipsychotic switching in bipolar disorders: a systematic review. (In general, antipsychotic switching, regardless of the route of drug administration, was well tolerated and no interference was shown in antipsychotic effectiveness during the interchange of drugs. Metabolic improvement was perceived when the switch involved antipsychotics with a low metabolic risk profile. Switch from quetiapine to lithium and from risperidone to olanzapine has proven successful. Switching to antipsychotics with low metabolic risk had some positive impact on several safety measures. In stabilized patients, the plateau cross-taper switch may be preferred.)

      • Monitoring pharmacotherapy response, safety, and tolerability to enhance adherence in bipolar disorder. (Among patients with bipolar disorder, treatment nonadherence can be triggered by lack of response or by medication-induced adverse effects. To track treatment response, clinicians can have patients complete daily life and mood charts to provide accurate information over time on patients' mood, adherence, side effects, and life events. Rating scales like the CGI-BP are also an option for assessing treatment response. In addition, clinicians should monitor patients for common side effects related to bipolar depression treatments, such as sedation and weight gain/metabolic abnormalities, which lead to increased medical problems and shortened life expectancy.)

      • The effectiveness of lurasidone as an adjunct to lithium or divalproex in the treatment of bipolar disorder. (Lurasidone was approved in 2010 for the treatment of schizophrenia and recently, 2013, for bipolar depression in monotherapy and an adjunct to lithium or valproate. Clinical trials have established that lurasidone adjuvant to lithium or valproate has more efficacy than the placebo and is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or the QT interval.)

      • Review of nutritional supplements for the treatment of bipolar depression. (The findings of this review do not support the routine use of nutritional supplements in the treatment or prophylaxis of BD depression. )

      • Clinical and regulatory implications of active run-in phases in long-term studies for bipolar disorder. (We assessed study designs of long-term studies for bipolar disorder of all second-generation antipsychotics (SGAs) submitted to the Food and Drug Administration (FDA). All randomized clinical trials selected patients who responded to acute treatment to increase the treatment effect observed in the long-term phase (enrichment design). Thus extrapolation of results from enrichment studies to the more general population of patients should be carried out cautiously because average treatment benefits are likely to be less in unselected patients.)

      • Meta-analysis of predictors of favorable employment outcomes among individuals with bipolar disorder. (Weighted correlation coefficients (Rw) were computed as effect sizes for each of the predictor variables. Significant predictors of favorable employment outcomes included: cognitive performance (e.g., verbal memory, Rw = 0.33; executive function, Rw = 0.26), sociodemographic factors (e.g., years of education, Rw = 0.23), course of illness (e.g., number of lifetime psychiatric hospitalizations, Rw = -0.35), symptomatology (e.g., depression, Rw = -0.25), and other personal factors (e.g., personality disorder, Rw = -0.49). Overall, the cognitive performance and course of illness had larger average effect size than symptomatology or sociodemographic factors on favorable employment outcomes.)

      • What is the evidence for the use of second-generation antipsychotic long-acting injectables as maintenance treatment in bipolar disorder? (Data available for the clinician assessing the interests of second-generation antipsychotics depot in long-term treatment of bipolar disorder are limited to risperidone. It seems particularly relevant for bipolar patients with poor adherence or early in the course of illness and can be used as monotherapy with manic polarity. It should always be considered for use in combination with at least one other mood stabilizer in patients with depressive polarity. )

      • Clinical decision making in the treatment of mixed states. (The strongest evidence in treating co-occurring manic and depressive symptoms was for monotherapy with aripiprazole, asenapine, extended release carbamazepine, valproate, olanzapine, and ziprasidone. As adjunctive treatment, the strongest evidence of efficacy was for olanzapine plus lithium or valproate. For maintenance, there is evidence for the efficacy of monotherapy with valproate, olanzapine, and quetiapine.)

      • Asenapine review, part II: clinical efficacy, safety and tolerability. (Asenapine's efficacy in the treatment of schizophrenia and in the acute management of bipolar manic or mixed episodes, within the recommended therapeutic dose range of 5 - 10 mg twice a day, is evidenced by a broad clinical development program. Asenapine's overall tolerability profile is notable for the potential for sedation (time-limited) and, to a lesser extent, extrapyramidal symptoms/akathisia, dizziness, and oral hypoesthesia. Asenapine's effects on weight and metabolic variables appear modest, as are its effects on the ECG QTc interval and on prolactin.)

      • Drug safety evaluation of olanzapine/fluoxetine combination. (Research confirms that the olanzapine/fluoxetine combination is an effective treatment for bipolar I depressive episodes, as well as major depressive episodes that have not responded to several adequate courses of antidepressant therapy. Its use as a first-line treatment for bipolar I depressive episodes and at a higher rung of algorithms for patients with treatment-resistant depression is limited by its propensity to cause weight gain and associated metabolic symptoms.)

      • Predicting bipolar disorder on the basis of phenomenology: implications for prevention and early intervention. ( It is not currently possible to anticipate those who will develop bipolar disorder solely on the basis of early phenomenology.)

      • Public health significance of bipolar disorder: implications for early intervention and prevention. (Bipolar Disorder (BD) is often recurrent and has an impact that goes well beyond symptomatic pathology. The burden it incurs is linked not only to its cardinal clinical features, but also to cognitive dysfunction, poor functional outcome, poor physical health, high rate of comorbidities, and suicide. At a societal level, BD induces enormous direct and indirect costs and has a major impact on caregivers. The available literature reveals a usually long delay between illness onset and the start of treatment, and the absence of specific guidelines for the treatment of the early phase of BD.)

      • Inhaled loxapine: A novel treatment for agitation in psychotic disorders. (Psychomotor agitation is a widespread clinical problem both in patients with schizophrenia and BD. It is a highly hazardous condition, imposing significant risks in psychiatric emergency, as expressedby elevated ratios of adverse events and traumatic experiences (both for patients and medical staff). The available anti-agitation drugs have numerous disadvantages. The orally administered medications (even though preferable to:patients) take hours or even-days for the therapeutic effect to emerge .(and also there is a risk of exacerbating agitation in between). Although rapid onset of action (15-45 minutes) is a noteworthy merit of intramuscular drugs, such an invasive strategy is far too often bound to patients' anxiety, resistance, and traumatic experiences. Inhaled loxapine seems to be an effective anti-agitation drug in treatment of patients with schizoplhenia and BD (with the onset of action similar to the one observed in intramuscular antipsychotics). However, this formulation of loxapine is distinguished by its non-invasive route of administration, as accompanied by markedly, low risk of side effects or adverse events.)

      • Mood stabilisers and pregnancy outcomes - a review. (Preliminary findings seem to identify lamotrigine as one ofthe safest antiepileptic drugs to be used in pregnancy. Teratogenity risk oftopiramate is still largely unknown and there are not enough studies to draw even preliminary conclusions. Preliminary studies failed to report an increased risk for major congenital malformations among gabapentin or.oxcarbazepine exposed pregnancies. Even if raising less concern when compared to valproate, carbamazepine should be avoided for its documented teratogenity risk. Valproate seems to be the worst considering major congenital malformations, specific malformations as,well as its detrimental effects on neurodevelopment. On the other hand, lithium might be considered a good option when treating pregnant women affected by bipolar disorder. Given the limited research on mood stabilizers in pregnancy, clinicians need to be very careful when treating child bearing age women.)

      • A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder. (Modafinil and armodafinil are recommended treatment adjuncts for refractory unipolar and bipolar depression. Until recently, RCT data on dopaminergic stimulants were too limited to warrant their use as first-line treatment adjuncts. However, the promising results of 1 recent lisdexamfetamine RCT, when considered in the context of the deleterious effect of subsyndromal depression, suggest consideration of dopaminergic medications in treatment-refractory unipolar or bipolar depression when modafinil is cost prohibitive or otherwise contraindicated.)

      • Treatment of bipolar depression: making sensible decisions. (A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.)

      • Balancing benefits and harms of treatments for acute bipolar depression. (The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials. [Administrator: In the treatment of bipolar depression, a number needed to treat (NNT) of 12 for lamotrigine and a NNT of 29 for antidepressants strongly suggests that these treatment effects are clinically insignificant.])

      • Differential diagnosis of bipolar disorder and major depressive disorder. (The estimated lifetime prevalence of major depressive disorder (i.e., unipolar depression) is over 3 and one-half times that of bipolar spectrum disorders. The clinical presentation of a major depressive episode in a bipolar disorder patient does not differ substantially from that of a patient with major depressive disorder (unipolar depression). Therefore, it is not surprising that without proper screening and comprehensive evaluation many patients with bipolar disorder may be misdiagnosed with major depressive disorder (unipolar depression). In general, antidepressants have demonstrated little or no efficacy for depressive episodes associated with bipolar disorder, and treatment guidelines recommend using antidepressants only as an adjunct to mood stabilizers for patients with bipolar disorder.)

    • Psychological Therapies

      • Evidence-based psychosocial treatments for child and adolescent bipolar spectrum disorders. (Thirteen psychosocial intervention trials for pediatric bipolar spectrum disorders (BPSDs) were identified via a comprehensive literature search. All interventions were examined adjunctive to pharmacotherapy and/or treatment as usual (TAU). Family psychoeducation plus skill building was probably efficacious (i.e., Multi-Family Psychoeducational Psychotherapy, Family-Focused Treatment); cognitive-behavioral therapy (CBT) was possibly efficacious. Dialectical behavior therapy (DBT) and interpersonal and social rhythm therapy (IPSRT) were experimental. In conclusion, psychosocial interventions that involve families, psychoeducation, and skill building may offer added benefit to pharmacotherapy and/or other TAU. Limitations of current research include few outcome studies, small samples, and failure to use stringent control conditions or randomization.)

      • Psychosocial interventions in bipolar disorder: what, for whom, and when. (A review was conducted with the aim to determine what the efficacious psychological treatments are, for whom and when. Randomized-controlled trials and key studies in adults with BD published until June 2013 were included. Outcomes vary between studies, with most trials focused on clinical variables like recurrence prevention or symptom reduction. The samples were usually in remission or with mild symptoms when recruited but there were a few studies with acute patients, which resulted in discrepant findings. The efficacy of psychological interventions seems to differ depending on the characteristics of the subjects and the course of the illness.)

      • Psychotherapeutic interventions in individuals at risk of developing bipolar disorder: a systematic review. (Only three completed studies were identified, two of which were randomized trials (n=77) and one was an open pilot study (n=13). Large multi-site studies with standardized procedures/manuals are needed.)

      • Self-management and bipolar disorder--a clinician's guide to the literature 2011-2014. (This review provides clinicians and individuals with bipolar disorder (BD) with an overview of evidence-based skills shown to be effective in BD and amenable to self-management including psychoeducation; monitoring moods, medications, and social function; sleep hygiene; setting goals and relapse plans; and healthy lifestyles (physical activity, healthy eating, weight loss and management, medical comorbidities). Research suggests that personally tailored interventions of longer duration and greater frequency may be necessary to achieve the maximal benefit among individuals with BD. Self-management of BD should complement rather than replace medical care.)

    • Miscellaneous

      • Diagnostic validity of comorbid bipolar disorder and obsessive-compulsive disorder: a systematic review. (At least 50% of bipolar disorder (BD) patients have an additional diagnosis, one of the most difficult to manage being obsessive-compulsive disorder (OCD). In this first systematic review of BD-OCD comorbidity, it appears that OC symptoms are usually secondary to BD, rather than representing a separate disease. Compared to non-comorbid subjects, BD-OCD has a more episodic course of OC symptoms (up to 75% vs. 3%), typically with worsening during depression (78%) and improvement during mania/hypomania (64%), as well as a higher total mean number of depressive episodes (8.9 +/- 4.2 vs. 4.1 +/- 2.7) and perhaps more antidepressant-induced mania/hypomania (39% vs. 9%).)

  • 2013 Research Review Articles

    • Biological Factors

      • Potential mechanisms of action of lithium in bipolar disorder. Current understanding (Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes.)

    • Pharmaceutical Therapies

      • Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis (Lithium is an effective treatment for reducing the risk of suicide in people with mood disorders. )

      • Treatment of bipolar disorder (Antipsychotic drugs are effective in the acute treatment of mania; their efficacy in the treatment of depression is variable with the clearest evidence for quetiapine. Despite their widespread use, considerable uncertainty and controversy remains about the use of antidepressant drugs in the management of depressive episodes. Lithium has the strongest evidence for long-term relapse prevention; the evidence for anticonvulsants such as divalproex and lamotrigine is less robust and there is much uncertainty about the longer term benefits of antipsychotics. Long-term maintenance and possibly acute stabilisation of depression can be enhanced by the combination of psychosocial treatments with drugs.)

      • A systematic review of the evidence on the treatment of rapid cycling bipolar disorder (Rapid cycling is associated with longer illness duration and greater illness severity in bipolar disorder. A literature review suggested that: (i) rapid cycling patients perform worse in the follow-up period; (ii) lithium and anticonvulsants have comparable efficacies; (iii) there is inconclusive evidence on the comparative acute or prophylactic efficacy of the combination of anticonvulsants versus anticonvulsant monotherapy; (iv) aripiprazole, olanzapine, and quetiapine are effective against acute bipolar episodes; (v) olanzapine and quetiapine appear to be equally effective to anticonvulsants during acute treatment; (vi) aripiprazole and olanzapine appear promising for the maintenance of response of rapid cyclers; and (vii) there might be an association between antidepressant use and the presence of rapid cycling.)

      • Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice (Asenapine displays quick and reliable effects on manic symptoms, very low risk of depressive switches, efficacy on depressive symptoms during manic and mixed episodes, usually good tolerability and continued longer-term efficacy on residual and subthreshold symptoms. The fast-dissolving sublingual route of administration may favor those who have difficulties in swallowing medications. The relatively low metabolic risk and the lack of anticholinergic side effects contribute to making this medication a useful tool for the treatment of patients with bipolar disorder.)

      • Consensus statement on the use of intramuscular aripiprazole for the rapid control of agitation in bipolar mania and schizophrenia (Of the available agents for rapid tranquillisation, aripiprazole demonstrated a favourable efficacy and safety profile both over the short-term - including in its intramuscular form (IM) - and in the long-term treatment of bipolar I disorder and schizophrenia)

      • Lower rate of depressive switch following antimanic treatment with second-generation antipsychotics versus haloperidol (Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.)

    • Psychological Therapies

      • Bipolar affective disorder and psychoeducation (Most bipolar patients cannot be treated only by drugs. Randomized controlled trials of cognitive behavioral therapy, interpersonal and social rhythm therapy, individual, group and family psychoeducation show that these approaches augment stabilizing effect of pharmacotherapy. Patients and their families should be educated about bipolar disorder, triggers, warning signs, mood relapse, suicidal ideation, and the effectiveness of early intervention to reduce complications.)

    • Miscellaneous

      • Bipolar depression in pediatric populations : epidemiology and management (Lithium and lamotrigine are feasible and tentatively efficacious options; however, treatment with quetiapine monotherapy may be no better than placebo. Furthermore, some youth may be at heightened risk for developing manic symptoms after treatment with selective serotonin reuptake inhibitors (SSRIs). Psychotherapy, either alone or adjunctively with medications, provides practitioners with a safe and feasible alternative.)

      • Bipolar disorders and comorbid anxiety: prognostic impact and therapeutic challenges (Many clinical and epidemiological studies have found much higher prevalence rates of generalized anxiety disorder, social phobia, obsessive-compulsive disorder, panic disorder and post-traumatic stress disorder in bipolar patients than in the general population, regardless of age. In the National Comorbidity Survey for instance, the diagnosis of at least one anxiety disorder was made for nearly 90% of bipolar subjects. Many studies point out the poorer outcome for bipolar patients with co-occurring anxiety symptoms: apart from the alarming increase of suicidal ideas and suicide attempts, authors have found a shorter duration of euthymia, more comorbid addictions, mixed states and rapid cycling, and lower response to treatments.)

  • 2009 Research Review Articles

  • 2008 Research Review Articles

  • 2007 Research Review Articles

  • 2006 Research Review Articles


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