Cytidine and Omega-3 Fatty Acids in Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

A Combination of Cytidine and Omega-3 Fatty Acids in Bipolar Disorder: Are There Additive or Synergistic Mood Stabilizing Effects?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00854737
• Other study ID #: 2009-P-000149
• Status: Completed
• Phase: Phase 2
• First received: February 27, 2009
• Last updated: April 19, 2012
• Start date: July 2004
• Est. completion date: July 2010

Study information

• Verified date: April 2012
• Source: Mclean Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The goal of the proposed clinical trial is to assess the effect of oral cytidine and omega-3 fatty acids (O3FA) on bipolar disorder symptoms. This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill subjects with bipolar disorder. During the 16 week period of the study, subjects are assigned to one of three groups: 1) omega-3 fatty acids + cytidine supplementation, 2) omega-3 fatty acids supplementation alone, and 3) placebo supplementation.

Description:

Previous studies examining the effect of omega-3 fatty acids on bipolar depression have had mixed results. Some studies have found that omega-3 fatty acids have a positive effect on bipolar depression symptoms, while other studies have found no difference between placebo and omega-3 fatty acid treatment.

The variable effects noted with omega-3 fatty acids may be due in part to a real effect with limited potency. Larger effects might be achieved by combining agents with synergistic effects.

Cytidine is necessary to form key intermediates in the biosynthesis of the phospholipids phosphatidylcholine and phosphatidylethanolamine, which are major components of eukaryotic cell membranes. Recent human studies by our group have shown that CDP-choline (a compound composed of cytidine and choline) can modify brain phospholipid synthesis in healthy adults and may have antidepressant effects (Babb et al., 1996; Babb et al., 2002; Carlezon et al., 2002; Renshaw et al., 1999). The combination of omega-fatty acids and the related pyrimidine, uridine, was associated with enhanced antidepressant-like activity in rats (Carlezon et al., 2005). Thus, the combination of omega-3 fatty acid and cytidine, which is interconverted with uridine in the body, may provide a safe and powerful way to treat bipolar disorder, especially bipolar depression.

This study is a 4-month, randomized, parallel-group, double-blind, placebo-controlled pilot study of a combination of cytidine and omega-3 fatty acids in 90 recently ill subjects with bipolar disorder. During the 16 week period of the study, subjects are assigned to one of three groups: 1) omega-3 fatty acids + cytidine supplementation, 2) omega-3 fatty acids supplementation alone, and 3) placebo supplementation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: July 2010
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• bipolar disorder

• mood episode within past year

• stable medication regimen

Exclusion Criteria:

• primary psychiatric disorder other than bipolar disorder

• significant suicide or homicide risk

• unstable medical conditions

• current or planned pregnancy

• lactose intolerance

• medications affecting lipid absorption or metabolism

• clozapine treatment

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Dietary Supplement:
• cytidine
cytidine (2g po daily for 4 months)
• omega-3 fatty acids
omega-3 fatty acids (4g po daily for 4 months)

Drug:
• placebo
sugar pill

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts
United States	Jersey Shore University Medical Center	Neptune	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	Stanley Medical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (5)

Babb SM, Appelmans KE, Renshaw PF, Wurtman RJ, Cohen BM. Differential effect of CDP-choline on brain cytosolic choline levels in younger and older subjects as measured by proton magnetic resonance spectroscopy. Psychopharmacology (Berl). 1996 Sep;127(2):88-94. — View Citation

Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA, Renshaw PF. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002 May;161(3):248-54. Epub 2002 Mar 22. — View Citation

Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50. — View Citation

Carlezon WA, Pliakas AM, Parow AM, Detke MJ, Cohen BM, Renshaw PF. Antidepressant-like effects of cytidine in the forced swim test in rats. Biol Psychiatry. 2002 Jun 1;51(11):882-9. — View Citation

Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999 May;56(5):407-12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mood Rating Scale Scores		weekly-biweekly	No
Secondary	Study Retention Time		4 months	No
Secondary	functional recovery		weekly-biweekly	No

External Links

•   hospital website with links to research group and studies