Bipolar depressive switch linked to antipsychotic use, major depressive episode frequency

Researchers have uncovered important factors associated with the switch from mania to depression among individuals with bipolar 1 disorder, according to results of a prospective observational study published in Journal of Clinical Psychiatry.

These included treatment with first- and second-generation antipsychotics, as well as depressive-predominant polarity, defined as two-thirds or more of a patient’s past episodes meeting criteria for major depressive episodes.

“In the past 30 years, patients’ switching from depression to mania has been a widely studied issue that originated a great debate on the possible trigger role of antidepressant drugs, particularly when they are used in monotherapy,” Giuseppe Maccariello, MD, of the department of experimental and clinic medicine at University of Pisa, and colleagues wrote. “However, the switch from mania to depression has been poorly investigated, and few studies have explored factors that may be associated with an increased risk [for] this particular phenomenon.”

Maccariello and colleagues sought to address this research gap by determining the predictors and prevalence of depressive switch among individuals with bipolar 1 disorder who required the initiation of treatment or change in form of treatment with oral antipsychotics or mood stabilizers for mania or mixed-mania. They conducted the 3-month, noninterventional study in 34 Italian psychiatric centers between April 2012 and April 2013 and included 234 patients aged 18 years or older who presented with a manic episode according to DSM-IV-TR criteria. At baseline and follow-up visits, they assessed patients using a multiple measures, such as the Clinical Global Impressions scale for use in bipolar illness (CGI-BP). Depressive switch served as the primary outcome, and they defined this a posteriori based on a Montgomery-Åsberg Depression Rating Scale total score of 15 or greater, as well as a Young Mania Rating Scale total score.

Results showed 26 patients (11.1%) switched to depression. Maccariello and colleagues noted associations between depressive switch and prescription of first- and second-generation antipsychotics (P = .017), depressive-predominant polarity (P = .012), CGI-BP total score at baseline (P = .024), depressive temperament and age at evaluation (P = .02).

“Prospective randomized controlled studies are now needed to formally test hypotheses about the causal relationship between antipsychotic use and mania-to-depression polarity conversion,” the researchers wrote. “Furthermore, longer-term follow-up studies comprising wider samples of patients may yield further information on rates and predictors of depressive switches, the understanding of which may help clinicians in the long-term management of [bipolar disorder].”