Despite their profitability and popularity, though, questions about how many people SSRIs really help and concerns about their significant side effects won’t go away. Some studies say that more than half the people who take antidepressants never get relief. Drug-placebo efficacy differences increase as a function of baseline severity, but are relatively small even for severely depressed patients, according to a study conducted by Irving Kirsch, Ph.D., a professor of psychology at the University of Hull, U.K., and professor emeritus at the University of Connecticut.
Additionally, the relationship between initial severity and antidepressant efficacy is often attributable to decreased responsiveness to placebo among very severely depressed patients rather than to increased responsiveness to medication. “There seems little reason to prescribe antidepressant medication to any but the most severely depressed patients,” Dr. Kirsch commented in his paper titled “Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration,” which appeared in PLoS Medicine in February 2008.
In a 2008 report published in The New England Journal of Medicine, Erick H. Turner, M.D., of Portland VA Medical Center and his colleagues said that the effectiveness of a dozen popular antidepressants had been exaggerated by selective publication of favorable results. According to published literature, it appeared that 94% of trials conducted were positive. By contrast, when Dr. Turner’s team included unpublished data submitted to the FDA, 51% of trials had positive results.
The researchers found that a total of 37 studies viewed by the FDA as having positive results were published, and one study viewed as positive was not published. On the other hand, three studies viewed by the FDA as having negative or questionable results were published, 22 negative studies were not published at all, and 11 were published in a way that, in the authors’ opinion, conveyed a positive outcome. The selective data publication presented doctors and patients with a less-than-accurate picture of how such drugs actually work, the authors concluded.
The currently available antidepressants have a range of adverse effects including nausea, sleep disturbance, fatigue, anxiety, sexual dysfunction in men, and suicidality. As with many medications that may be required chronically by otherwise healthy people, the side-effect tolerance level is lower than for medications for critically ill individuals. The resulting increase in FDA scrutiny makes it harder to get these drugs to market. Another drawback is that most typical antidepressants have a delayed onset of action (two to six weeks) and are usually administered for anywhere from months to years.
Now pharma companies are mixing stronger medicines, or at least different ones, with antidepressants as adjunctive therapies. On December 4, AstraZeneca received approval from FDA for a label extension for once-daily Seroquel, which is approved for management of schizophrenia, bipolar I mania, bipolar I depression, bipolar II depression, and used off-label for a variety of other purposes including insomnia and anxiety disorders. For AstraZeneca, Seroquel 2008 revenues were up 11% over 2007 to $4.452 billion. U.S. sales were $3.02 billion, a 5% increase over 2007.
The latest sanction includes the use of Seroquel as an adjunctive treatment to antidepressants in adults with major depressive disorder. The agency also required that AstraZeneca implement a Risk Evaluation and Mitigation Strategy through a medication guide and periodic assessments that will include a survey of patients’ understanding of the potential risks of the drug.
For part two of this article—Finding Newer Molecular Targets for Antidepressants—click here.