Risk of psychosis exacerbation by tricyclic antidepressants in unipolar Major Depressive Disorder with psychotic features.
We conducted a systematic review of the published trials in unipolar Major Depressive Disorder with psychotic features (MDDP) to examine the risk of psychosis exacerbation by antidepressants. We searched Medline, Cochrane Central Register of Controlled Trials, PsychINFO, and EMBASE for English language, controlled, open or retrospective acute antidepressant and/or antipsychotic treatment studies of unipolar MDDP. Studies without a clear delineation of treatment course or between bipolar disorder and unipolar MDDP were excluded. We evaluated studies for the number of subjects with psychosis exacerbation, and contacted the corresponding author for ambiguous cases. Studies in which we were unable to determine rates of psychosis exacerbation were excluded. Psychosis exacerbation was determined on a categorical basis, and analyzed with Fisher's exact test, a modified Wald confidence interval and odds ratio. 20 studies meeting criteria provided sufficient adverse event reporting for inclusion. 15 of 177 subjects (8.5%) on antidepressant monotherapy had a psychosis exacerbation, 8 of whom were on tricyclics. 2 of 129 subjects on either antipsychotic or combination treatment had a psychosis exacerbation. Tricyclic monotherapy was significantly more likely to be temporally associated with psychosis exacerbation (p=0.007). Limitations include the small number of placebo-controlled trials, and numerous studies in which the relevant information was missing. Additionally, most trials were designed as treatment outcome studies, and not to determine the rate of psychosis exacerbation. Although rare, the present study indicates that tricyclic monotherapy may be temporally associated with an exacerbation of psychotic symptoms in patients with unipolar MDDP, potentially worsening prognosis.