Clinical trial NCT00854737: Cytidine and Omega-3 Fatty Acids in Bipolar Disorder
Official title: A Combination of Cytidine and Omega-3 Fatty Acids in Bipolar Disorder: Are There Additive or Synergistic Mood Stabilizing Effects?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bipolar Disorder
Keywords: bipolar disorder
bipolar depression
bipolar mania
manic depression
depression
mania
hypomania
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2009-03-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mood Rating Scale Scores
timeFrame: weekly-biweekly
Secondary outcomes:
measure: Study Retention Time
timeFrame: 4 months
measure: functional recovery
timeFrame: weekly-biweekly
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
Study officials:
affiliation: Mclean Hospital
name: Beth L Murphy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1007/BF02805979.
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. doi: 10.1007/s00213-002-1045-y. Epub 2002 Mar 22.
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. doi: 10.1016/j.biopsych.2004.11.038.
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. doi: 10.1001/archpsyc.56.5.407.
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. doi: 10.1016/s0006-3223(01)01344-0.
citation: Murphy BL, Stoll AL, Harris PQ, Ravichandran C, Babb SM, Carlezon WA Jr, Cohen BM. Omega-3 fatty acid treatment, with or without cytidine, fails to show therapeutic properties in bipolar disorder: a double-blind, randomized add-on clinical trial. J Clin Psychopharmacol. 2012 Oct;32(5):699-703. doi: 10.1097/JCP.0b013e318266854c.