Although guidelines state that antidepressant treatment should continue for up to six months after an acute depressive illness, there is considerable variation in practice and widespread uncertainty about the optimal duration of therapy. Geddes and colleagues reviewed research evidence to determine whether continued treatment reduces the risk of relapse after an acute depressive illness and to establish the optimal duration of treatment.
They reviewed all published and unpublished randomized placebo-controlled trials of at least one month of continued treatment after response to antidepressant medication for an acute depressive illness. Two independent reviewers assessed each trial for methodologic quality, and the relevant data were extracted. More than 120 reports initially were identified; 31 trials with 4,410 participants met inclusion criteria and had suitable data available for analysis. The trials followed patients from six to 36 months; one year of follow-up was most common.
For all types of antidepressant medication, continued therapy consistently reduced the risk of relapse by about 70 percent. The average relapse rate for placebo was 41 percent compared with 18 percent for antidepressant therapy. The longer trials in which patients were treated for two to three years showed that the risk of relapse was higher in the first year after an acute episode, but that antidepressant treatment was as effective during the first and second years in preventing relapse. The rates of withdrawal from therapy were 18 percent in treated patients and 15 percent in control subjects. The limited data on suicide prevented comparison between treated and control groups.
The authors conclude that continued antidepressant therapy reduced the odds of relapse by about two thirds, which reduced the absolute risk by about one half. The results were similar for different classes of antidepressant drugs and subgroups of patients. Relatively few studies followed patients for longer than 12 months, and the authors call for further studies to determine the optimal duration of therapy and to identify subgroups of patients who might benefit most from continued therapy. In the interim, the authors recommend that at least one additional year of treatment be considered for patients who are still at appreciable risk of relapse after four to six months of treatment after a depressive illness.