Omega-3 Fatty Acid Treatment, With or Without Cytidine,... : Journal of Clinical Psychopharmacology (original) (raw)

Brief Reports

Omega-3 Fatty Acid Treatment, With or Without Cytidine, Fails to Show Therapeutic Properties in Bipolar Disorder

Murphy, Beth L. MD, PhD*†; Stoll, Andrew L. MD†‡; Harris, Peter Q. MD, PhD§; Ravichandran, Caitlin PhD*∥; Babb, Suzann M. MS*†; Carlezon, William A. Jr PhD*†; Cohen, Bruce M. MD, PhD*†

From the *Harvard Medical School, Boston; †Frazier Research Institute; ‡Psychopharmacology Research Laboratory / Program for the Development of Natural and Novel Treatments for Bipolar Disorder, McLean Hospital, Belmont, MA; §Jersey Shore University Medical Center, Neptune, NJ; and ∥Laboratory for Psychiatric Biostatistics, McLean Hospital, Belmont, MA.

Received July 20, 2011; accepted after revision February 17, 2012.

Reprints: Bruce M. Cohen, MD, PhD, McLean Hospital, 115 Mill St, Belmont, MA 02478 (e-mail: [email protected]).

Supported by Stanley Medical Research Institute, Chevy Chase, MD (B.M.C.).

ClinicalTrials.gov Identifier: NCT00854737.

Abstract

Objective

This study aimed to test the effects of omega-3 fatty acids (O3FA), given as fish oil capsules, with and without oral cytidine (CYT), a pyrimidine with reported preclinical and clinical antidepressant-like effects, in patients with bipolar disorder (BD).

Methods

A total of 45 outpatients with diagnosed BD (type I) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Text Revision, were recruited for this 4-month, randomized, double-blind, placebo-controlled, add-on study. Treatment groups were (1) oral CYT + O3FA, (2) placebo + O3FA, and (3) placebo + placebo control. O3FA was given 2 g twice a day and CYT was administered as 1 g twice a day.

Results

There was no statistically significant difference among the groups in the primary outcome: study retention. Clinical measures improved in all treatment groups, and there were no significant differences between groups, including change in probability of symptoms of depression or mania, change in positive ratings of depression or mania, or change in Global Assessment of Functioning scores. Neither CYT + O3FA nor placebo + O3FA treatment was superior to placebo treatment. Rather, there was a statistically nonsignificant trend for both groups treated with O3FA to do worse than the placebo group.

Conclusions

Despite preclinical studies suggesting that the effect of O3FA might be augmented with pyrimidines, add-on CYT did not substantially improve mood symptoms in BD. In addition, although a power analysis indicated that the sample size would be adequate to see beneficial effects similar to those previously reported, O3FA treatment by itself was not superior to placebo for BD.