Onset of improvement under fluoxetine and moclobemide

In a meta-analysis of the selective serotonin reuptake inhibitor fluoxetine (n = 440) and the reversible and selective monoamine oxidase-A inhibitor moclobemide (n = 437) we investigated the time course of improvement over 6 weeks for these two classes of anti-depressants. Two different methods of approach were applied: (1) repeated measurement analysis of variance in combination with regression analysis, and (2) a survival-analytical approach that allowed us to determine onset of improvement for the individual patient, to distinguish between early and late improvers, to assess the predictive value of early improvement, and to adequately process premature withdrawals. The two antidepressants of large biochemical and pharmacological differences yielded virtually identical response- and drop-out rates, and exhibited no difference with respect to the time course of improvement. Onset of improvement occurred in more than half of the patients within the first 2 weeks of treatment, and early improvement was highly predictive of later outcome. In particular, there was no indication for a delayed onset of action of antidepressants. We suggest that future studies should be standardised with respect to washout period and sufficiently dense assessments during the first 2 weeks of trial. Thus, patient samples can be subdivided reproducibly into early-, late-, partial- and non-remitters. This, in turn, may help to identify "true" drug responders, and to discover why in some patients recovery becomes "stuck". Data already held by the pharmaceutical companies should be reanalysed in this respect.