Acute, maintenance citalopram treatment did not benefit patients with bipolar depression

Citalopram combined with standard mood stabilizers did not offer clinically meaningful benefit vs. placebo for acute or maintenance treatment of bipolar depression, according to study results published in Journal of Clinical Psychiatry.

“The most recent meta-analysis of randomized clinical trials of antidepressants for bipolar depression found them to be ineffective, and some bipolar experts have urged caution,” S. Nassir Ghaemi, MD, MPH, of the department of psychiatry at Tufts University School of Medicine, and colleagues wrote. “In addition, meta-analyses of maintenance treatment of depressive episodes also failed to find evidence of preventive efficacy, though most studies involved older agents.”

Moreover, prior studies suggested risk for induction of acute mania, primarily linked with older tricyclic antidepressants rather than newer serotonin reuptake inhibitors. In the current randomized, double-blind, placebo-controlled trial, Ghaemi and colleagues sought to evaluate the safety and efficacy of citalopram in the acute and maintenance phases of bipolar depression. They randomly assigned 119 individuals with acute major depressive episode diagnosed with DSM-IV type 1 or 2 bipolar disorder to citalopram or placebo, which were added to standard mood stabilizers. The researchers followed them for 6 weeks for acute efficacy, which was the primary outcome, and up to 1 year for maintenance efficacy, which was the secondary outcome. Participants provided data via the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mania Rating Scale of the Schedule for Affective Disorders and Schizophrenia (MRS-SADS).

Results showed a change in mean ±SD MADRS score from a baseline value of 27.4±9.1 to 13.1±8.4 at the end of the acute phase for citalopram vs. a change from 27.4±7.3 to 15.2±9.9 for placebo; this difference was clinically and statistically nonsignificant, according to the researchers. Further, citalopram did not demonstrate better maintenance efficacy than placebo. Both groups exhibited similar manic/hypomanic episodes, and those with type 2 illness did not have better outcomes vs. those with type 1 illness. MRS-SADS scores were greater overall in maintenance treatment, particularly among individuals with a rapid-cycling illness course

“The results of this [randomized clinical trial] would suggest caution in the use of antidepressants in bipolar illness, mainly because of lack of clinically meaningful efficacy for acute and maintenance treatment and secondarily due to long-term manic worsening in rapid-cycling subjects,” Ghaemi and colleagues wrote.