Comparing onset of effect of antidepressants: Pragmatic considerations on methods and end-points

There is no accepted definition of what constitutes onset of antidepressant effect, and this limits evaluation of the validity of many comparative reports. In order to clarify the nature of the comparative methodology required, it is proposed that two distinct research questions are separated conceptually: 1) when do antidepressant drugs begin to clinically act? and 2) do all antidepressant drugs produce relief of symptoms in patients within a similar time period? A methodological distinction may also be made in terms of whether to assess the onset of effect of an antidepressant as having an absolute quality ("fast") or as being fast relative to other treatments ("faster"). The choice of aim will help to define the methodological approach, the applicability of the findings and the difficulties to be addressed. Describing an antidepressant as showing a "fast" or "faster" onset of response requires that any description attempts to define (in terms that may be generalised) the nature of the comparison (faster than what?), the nature of the effect (faster to do what?) and the population in whom this effect may be expected (faster in whom?). Some details of methodological approaches are reviewed, and suggestions for study designs are made.