Nil Kaymaz, MD; Jim van Os, MD, PhD; Anton J. M. Loonen, MD, PharmD, PhD; and Willem A. Nolen, MD, PhD
Background: Antidepressants are effective in the prevention of
relapse after remission from an acute depressive episode. It is unclear,
however, to what degree duration of the continuation phase, level of abruptness
of antidepressant discontinuation, or the number of previous episodes moderate
the prophylactic effect of antidepressants.
Data Sources: Searches were conducted to identify all
published randomized, placebo-controlled, double-blind clinical trials
available for review by May 2007 on the efficacy of continuation or maintenance
treatment of major depressive disorder with either selective serotonin reuptake
inhibitors (SSRIs) or tricyclic antidepressants (TCAs) that included patients
entering a maintenance phase after achieving remission from the acute phase.
The MEDLINE and EMBASE databases were searched using the terms depression,
antidepressants, discontinuation, and maintenance treatment; this
was followed by reference checks of articles thus identified. In addition, the
Cochrane Library was also searched using the same terms. Some authors of the
identified papers were contacted for specific data.
Data Synthesis: Data were collected from 30 trials with 4890
participating patients. The overall reduction of relapse risk in the
maintenance phase was highly significant for both SSRIs (OR = 0.24, 95% CI =
0.20 to 0.29) and TCAs (OR = 0.29, 95% CI = 0.23 to 0.38) over 1 year of
follow-up of maintenance treatment. The prophylactic effect appeared to be
constant over the length of the continuation phase. Recurrent episode patients
experienced less protection from antidepressants over the maintenance phase (OR
= 0.37, 95% CI = 0.31 to 0.44) than single episode patients (OR = 0.12, 95% CI
= 0.06 to 0.26).
Conclusions: Antidepressants robustly reduce relapse risk in
the maintenance phase, regardless of a number of clinical and pharmacologic
factors. There is evidence, however, that with increasing number of episodes,
patients develop a relative resistance against the prophylactic properties of
antidepressant medication.
J Clin Psychiatry 2008;69(9):1423-1436
© Copyright 2008 Physicians Postgraduate Press, Inc.