The antidepressant debate continues

In her March 2002 editorial, Dr Moncrieff raises doubts about the efficacy of antidepressant drugs, and argues that side-effects of the active drug may explain some of the differences owing to the associated increased expectancy of a positive effect. Our 24-week study (Malt et al, 1999) comparing the efficacy of empathic primarycare counselling and support combined with placebo, a selective serotonin reuptake inhibitor (sertraline) or an a2/5-HT2/3 antagonist (mianserin) in 372 subjects with depressed mood does not support her arguments. In our study the general practitioners were required to systematically explore possible side-effects. This method yields a greater prevalence of side-effects than when only spontaneously reported side-effects are considered. The mean numbers of baselinecorrected UKU-elicited side-effects (Lingjaerde et al, 1987) during the study were 7.11, 6.51 and 6.45 after 8 weeks of treatment with sertraline, mianserin and placebo, respectively, and 3.16, 3.09 and 3.02 after 24 weeks of treatment (NS). This means that prevalence of side-effects is unlikely to explain the difference in response. Another observation arguing against the hypothesis that non-specific side-effects may explain differences between active drug and placebo is the fact that we obtained differences in response over time among the three treatment arms. As would be expected by the pharmacodynamic profiles of the drugs, mianserin induced a faster initial response, while sertraline demonstrated an advantage in the long run explained by better efficacy among subjects with high neuroticism. At the end of the study, the physicians were not able to identify reliably the treatment given to each of their patients. Furthermore, differences in effect size between the treatments (see Table 1) clearly demonstrated the advantage of antidepressant drugs on core symptoms of depression. These differences are well beyond the estimated mean effect size of 0.27 reported for active placebo. Instead of questioning the efficacy of antidepressant drugs in depression, attention should be directed at the critical question regarding the characteristics of those patients who will benefit from receiving antidepressant drugs in addition to psychological intervention.