Effectiveness of selective serotonin reuptake inhibitors

As a family physician I see many patients with mood disorders and selective serotonin reuptake inhibitors are an important therapeutic option for them. I have the clinical impression that drugs in this class can be very effective, and I prescribe them often. I was thus interested to read what the systematic review by Barbui and colleagues revealed about their effectiveness.1

I was disappointed and puzzled by the bizarre primary outcome measure selected by the authors: the proportion of patients who left a study early for any reason. Consider the ideal situation in which no one in either study arm drops out; it would be impossible for the active treatment to be better than placebo even if all treated subjects went into remission. How can this be a measure of effectiveness?

In my practice, the biggest challenge is persuading patients to persist with therapy through the first few days of unpleasant side effects until the beneficial effects become manifest. I consider early dropout to be a failure of my persuasive powers and not an indication that the therapy is ineffective. I believe that it is important to distinguish between dropout in the first days of treatment, which is a consequence of the predictable and often transitory unpleasant side effects, and delayed dropout, which may reflect treatment failure. The authors failed to stratify their analysis on the time of dropout and their analysis is thus not informative with respect to dropout for the important end points of treatment failure or persistent side effects.

As a clinician I am primarily interested in the effectiveness of a drug in those who actually take it. It is thus disappointing that the authors gave short shrift to their secondary outcome measures, all of which showed a significant benefit of active treatment.