Publication Bias Favoring Newer Antipsychotics

Phillip W. Long, M.D.
July 28, 2002

Recently many mental health websites have, unwittingly, developed a strong publication bias favoring the newer ("atypical") antipsychotic medications (e.g., Zyprexa, Risperdal, Seroquel, Clozaril) over the older conventional antipsychotic medications (e.g., flupenthixol, loxapine, perphenazine).

Research is showing that there is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics - they merely have different side-effects (e.g., Zyprexa, Risperidal, Seroquel, and Clozaril). There is no difference between the newer ("atypical") antipsychotic medications and conventional antipsychotic medications on broad outcomes such as mortality, ability to work, suitability for hospital discharge, or relapse rates.

Many of the conventional antipsychotic medications often cause unacceptible muscle tremor and stiffness; whereas the newer ("atypical") antipsychotic medications don't cause these adverse effects. However, the newer ("atypical") antipsychotic medications often cause unacceptible weight gain and sleeping 12+ hours a day. I have had many patients on Clozaril or Zyprexa that have gained 40+ pounds (and have lost it once off these drugs); hence I can personally attest to the seriousness of these adverse effects.

These serious adverse effects of many of our newer ("atypical") antipsychotic medications were not reported when these medications were initially licenced. The original researchers, however, should have known that there was something seriously wrong with many of these newer ("atypical") antipsychotic medications, because the original studies would often have 83% drop-out rates by 1 year. However, due to an extremely bad statistical convention, the "Last Observation Carried Forward", these unbelievably high drop-out rates were statistically erased and basically hidden from public view.

Many patients do benefit from our newer ("atypical") antipsychotic medications. In my psychiatric practice, approximately one-third of all my patients with Schizophrenia that start on Zyprexa, stay on this medication. The two-thirds of my patients with Schizophrenia who quit Zyprexa, usually subsequently benefit from another antipsychotic medication (costing hundreds of dollars a month less than Zyprexa).

I am not against the newer ("atypical") antipsychotic medications, I just believe that their benefits have been incredibly "over-sold" by the pharmaceutical industry. Some conventional antipsychotic medications have far fewer adverse effects than the newer ("atypical") antipsychotic medications. In particular, flupenthixol is an inexpensive, conventional antipsychotic medication that is usually free of bothersome adverse effects (like tremor, stiffness, weight gain or over-sedation). In Canada, an average monthly dose of Zyprexa costs $385, and flupenthixol costs $26. Yet clinically, I find both of these medications to be equally effective.

No matter how initially promising a new ("atypical") antipsychotic medication might be, if it has a 83% drop-out rate by 1 year, it is not an effective treatment. Although I have singled out my experience with Zyprexa, I believe the same criticisms (to a lesser degree) apply to the other newer ("atypical") antipsychotic medications

How did this publication bias favoring the newer ("atypical") antipsychotic medications occur?

First, it starts when a mental health website innocently starts to publish pharmaceutical company press releases. These press releases always "over-sell" the benefits of the company's medication, and minimize the medication's short-comings. This highly biased reporting should never be published on the internet. Yet many otherwise excellent mental health websites publish these press releases.

This distortion of the truth becomes much more pronounced when a mental health website accepts pharmaceutical company financial sponsorship. These pharmaceutically sponsored websites often become an "infomercial" for their sponsor.

Thus, in conclusion, I would like to make three proposals:

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