That Overlooked Statistic

Another article on this website refers to a University of Connecticut/George
Washington University study that analyzed an FDA database of 47 placebo-controlled clinical trials involving six antidepressants. These included failed studies that weren't published. The study caused a sensation in media and academic circles when it was revealed that 80 percent of the medication response in the combined drug groups was duplicated in the placebo groups, and that the mean difference between the drug and placebo was a "clinically insignificant" two points on the Hamilton Depression Scale.

An eye-popping finding of equal import, which the study's authors Irving Kirsch PhD and Thomas Moore PhD are making in public presentations, is that only 63 percent of those taking antidepressants in the pooled drug studies completed the four to eight-week trials. The combined placebo group recorded a similar figure of 60 percent. Only four of the studies achieved the 70 percent completion rate sought by the FDA.

In other words, nearly 40 percent of those taking antidepressants failed to make it through the four to eight weeks of a normal drug trial. This figure dwarfs the numbers the drug companies in the study put on their product
information, namely:

Prozac 12 percent; Paxil 20 percent; Zoloft 14 percent; Effexor XR 11 percent; Serzone 16 percent; Celexa 15 percent.

An important qualifier is the drop-outs in the separate drug studies were due to adverse events only, but the results fare miserably against other classes of drugs using the same measure. For example, only 1.4 percent of patients discontinued the cholesterol drug Zocor due to adverse events, seven percent quit the arthritis drug Celebrex (which had much longer trials), and just 1.5 percent said no to the heart drug Norvasc.

As to what constitutes an unacceptable drop-out rate in other branches of medicine, AstraZeneca reported ending a 1997 study of its breast cancer drug Nolvadex (tamoxifen) due to 26 percent of patients quitting, but this was after one year. A 26 percent drop-out rate in a year-long psychiatric drug study, by contrast, would have its manufacturer trumpeting the medication's safety and tolerability. Oddly enough, a small pilot study recently tested tamoxifen for mania. It will be interesting to compare drop-out rates if larger studies are done.

[Two weeks after publishing this, Lundbeck AS, which manufactures the antidepressant Lexapro in Europe, announced the completion of a "successful" 52-week study in which - yes - 26 percent of the patients dropped out.]

Meanwhile, it is instructive to take a closer look at the Paxil figures. Paxil represents a virtual Swiss Army knife of antidepressants, with a use for any number of psychiatric situations, FDA approved. Whereas 20 percent of Paxil's depression patients dropped out of trials due to adverse events, according to the manufacturer's data, only nine percent of those with panic disorder quit, followed by 11 percent for generalized anxiety disorder, 12 percent each for OCD and PTSD, and 16 percent for social anxiety disorder.

In theory, these numbers should have been about equal across all groups, but depression sufferers clearly found much more not to like besides just side effects, such as maybe their meds not working. Doses are typically started at the low end of the scale, with the clinical benefit not beginning to show until the second week and a meaningful response not occurring until the fourth to sixth week or longer, if at all. Perversely, the side effects make themselves felt at once. Not exactly an inducement to stay on one's meds, not even the ones that come as orange-flavored sol-tabs.

So what is the most meaningful figure in an antidepressant trial? Apparently not the response rate, not the remission rate, not the Hamilton Depression scores. It's the drop-out rate, way too high whether going by industry figures or the FDA database. Clearly we are sending an unequivocally strong
message that our medications leave much to be desired. Are any drug companies listening?

For three free online issues of McMan's Depression and Bipolar Weekly, email me and put "Sample" in the heading and your email address in the body.

Issues and Advocacy articles All articles

Post your opinion here.

John McManamy

Order my book on Amazon

Order now

Newsletter

Your online source for issues that matter to you.

For free samples, email me and put "Sample" in the heading and your email address in the body.

Find out more.

Bookstore

Shop for depression and bipolar books online here.