Clinical trials of antidepressants: the hidden face: where locus of control appears to play a key role in depression outcome

It remains difficult to determine in what measure improvements observed in clinical trials of antidepressants may be attributable to the psychological predispositions of the subjects. The present article focuses on the effect of a psychological variable, the Health Locus of Control, which measures the extent of a subject's belief that he is in control over his own health. The hypothesis is that depressed subjects whose locus of control is internal, i.e. who perceive themselves to be in control, rather than external, i.e. control perceived as being in others or just chance, will improve more markedly and consistently on the Hamilton Depression Rating Scale, across a number of clinical trials. Forty-nine depressive patients undergoing treatment with four different compounds were included, after a week's placebo run-in period, in a classical 42-day follow-up study comprising visits on days –7, 0, 10, 21; and 42. Interactions between the type of locus of control and the clinical course were investigated by MANOVA. Results show that with a classical design of clinical trials of antidepressants, locus of control plays a significant role if it is internal (P<0.001) in consolidating the improvement process, and that this is true irrespective of type of antidepressant. The relationship between the concept of locus of control and placebo effect is discussed.