Role of the Placebo Response in the Treatment of Depressive Disorders

Results from placebo-controlled trials of antidepressants have demonstrated that a large proportion of depressed patients show a significant improvement of symptoms while receiving placebo. In some patients, the improvement may be due to the natural course of the illness, independent of any therapeutic intervention, but in others it may be due to nonspecific therapeutic factors. Presumably, the latter are at least as relevant in clinical practice as in the research setting. The factors responsible for the placebo effect are unknown. However, several clinical variables are associated with an improvement in depressed patients who receive placebo. The most consistent correlation is a negative one between the duration of the presenting episode and a diminished placebo response. In addition, the role of expectation or hope has been emphasised. The placebo response appears to be less stable than the improvement attributable to drugs. In controlled antidepressant trials, a significant proportion of placebo responders will relapse during follow-up. Two patterns of placebo response have been identified; one is characterised by an early, abrupt, nonsustained improvement and the other by a gradual sustained response. The instability of the placebo response may explain why some patients lose an initial apparent antidepressant response. It was recently proposed that the initial treatment for a sizeable proportion of depressed patients should be 4 to 6 weeks of placebo. This has been rejected on practical grounds. Although placebo treatment of depression cannot be fully advocated, knowledge of the determinants and course of the placebo response can be used to guide clinical management.