Geodon Ineffective for Bipolar Depression; or, Watch ClinicalTrials.gov in Action!

According to results recently posted by Pfizer on ClinicalTrials.gov, the antipsychotic Geodon is not effective for the treatment of depression in patients with bipolar disorder.

Atypical antipsychotics, like Geodon, are all FDA-approved for the manic phase of bipolar disorder, but only Seroquel is approved for treating bipolar depression, though just how effective it is remains controversial.

The Geodon results are noteworthy because the only reason we even know about them is that drug companies are now required to post the results of clinical trials on the clinical trials registry. This was a requirement of the FDA Amendments Act of 2007; before this act, companies could voluntarily post the protocol of a research study on the registry, but it was not compulsory and there was no requirement that they ever publish the results. The FDAAA, among other things, both make it mandatory for companies to post new trials on the registry, and, even more significantly, required that they actually post the results of those trials. This latter requirement did not kick in until September of 2008.

In the past, companies have simply buried research results if they showed that their drugs were ineffective. For example, Erick Turner and his colleagues published this paper in the New England Journal of Medicine showing that drug companies had selectively published only the positive findings regarding antidepressant drugs. Specifically, companies had published 94% of all their positive studies of antidepressants, but only 38% of their negative studies; furthermore, even most of the published “negative” studies had been spun so that once in print they appeared to be far more positive than they were.

From the standpoint of a psychiatrist trying to figure out which drugs work, the bottom line was this: if I relied on the published medical literature for information (and what else can I rely on?), it would seem as though 94% of all antidepressant trials are positive. But if I had access to the suppressed data as well, the true figure is that only about half--51%--of trials are positive.

To come back to Geodon, before FDAAA, Pfizer would presumably have either not published the results of the recent bipolar depression studies, or would have published them as falsely positive. Doctors would have continued to prescribe the drug in this condition under the false assumption that if one atypical antipsychotic is effective (Seroquel), then they must all be effective.

Here is a very brief run-down of the two studies, both of which were placebo-controlled, double blind, multi-site trials of patients with bipolar disorder I who were depressed when they entered the studies. One of them, identified as study NCT00282464, was a 6-week flexible dose study comparing Geodon with placebo, and the other one, NCT00141271 was a fixed dose trial comparing both high and low dose Geodon with placebo.

The studies were complex, with many different outcome variables assessed, but the bottom line is that neither of them managed to show that Geodon was significantly more effective than placebo on the primary depression rating scales. Will the results be spun in various ways to make them look good? You betcha. We will undoubtedly see publications coming out of this data that will emphasize certain outcome scales, at certain time-points, in certain kinds of patients, etc…. The data will be tweaked to nth degree.

But at least we now have a law on the books requiring companies to post the data for all to see, so that we may judge for ourselves whether published papers are accurate renditions of the data. For that, we should be grateful to both Congress and to former President Bush, who signed the legislation into law.