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

Journal of Clinical Psychopharmacology

Volumn 32, Issue 5, 2012, Pages 699-703

  Murphy, Beth L ^a,b   Stoll, Andrew L ^b,c   Harris, Peter Q ^d   Ravichandran, Caitlin ^a,c   Babb, Suzann M ^a,b   Carlezon, William A ^a,b   Cohen, Bruce M ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b Frazier Research Institute   (United States)

^c MCLEAN HOSPITAL   (United States)

^d JERSEY SHORE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

bipolar disorder; clinical trial; cytidine; mood stabilizers; omega 3 fatty acids

Indexed keywords

CYTIDINE; OMEGA 3 FATTY ACID; PLACEBO;

ARTICLE; BIPOLAR I DISORDER; CLINICAL ARTICLE; CONTROLLED STUDY; DEPRESSION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; GASTROINTESTINAL SYMPTOM; HUMAN; MALE; MANIA; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT;

ADULT; BIPOLAR DISORDER; CYTIDINE; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FATTY ACIDS, OMEGA-3; FEMALE; HUMANS; MALE; MIDDLE AGED; TREATMENT FAILURE;

EID: 84865862410     PISSN: 02710749     EISSN: 1533712X     Source Type: Journal    
DOI: 10.1097/JCP.0b013e318266854c     Document Type: Article

References (32)

1. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006;67:1954-1967.
2. Freeman MP. Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry. 2000;12:159-165.
3. Montgomery P, Richardson AJ. Omega-3 fatty acids for bipolar disorder. Cochrane Database Syst Rev. 2008;(2):CD005169.
4. Hibbeln JR. Fish consumption and major depression. Lancet. 1998;351:1213.
5. Hibbeln JR. From homicide to happinessVa commentary on omega-3 fatty acids in human society. Cleave Award Lecture. Nutr Health. 2007;19:9-19.
6. Hibbeln JR. Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet. 2009;99:17-30.
7. Peet M, Murphy B, Shay J, et al. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998;43:315-319.
8. Yao J, Stanley JA, Reddy RD, et al. Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites. Biol Psychiatry. 2002;52:823-830.
9. Mahadik SP, Mukherjee S, Horrobin DF, et al. Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects. Psychiatry Res. 1996;63:133-142.
10. Soares JC, Dippold CS, Wells KF, et al. Increased platelet membrane phosphatidylinositol-4,5-bisphosphate in drug-free depressed bipolar patients. Neurosci Lett. 2001;299:150-152.
11. Huang SY, Yang HT, Chiu CC, et al. Omega-3 fatty acids on the forced-swimming test. J Psychiatr Res. 2008;42:58-63.
12. Gracious BL, Chirieac MC, Costescu S, et al. Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder. Bipolar Disord. 2010;12:142-154.
13. Sinclair AJ, Begg D, Mathai M, et al. Omega 3 fatty acids and the brain: review of studies in depression. Asia Pac J Clin Nutr. 2007;16 (suppl 1):391-397.
14. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007;68:1056-1061.
15. Sontrop J, Campbell MK. Omega-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Prev Med. 2006;42:4-13.
16. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry. 2006;188:46-50.
17. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56:407-412.
18. Wurtman RJ, Regan M, Ulus I, et al. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol. 2000;60:989-992.
19. Cornford EM, Oldendorf WH. Independent blood-brain barrier transport systems for nucleic acid precursors. Biochim Biophys Acta. 1975;395:211-219.
20. Richardson UI, Watkins CJ, Pierre C, et al. Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res. 2003;971:161-167.
21. Kennedy EP, Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956;222:193-214.
22. Knapp S, Wurtman RJ. Enhancement of free fatty acid incorporation into phospholipids by choline plus cytidine. Brain Res. 1999;822:52-59.
23. Wurtman RJ, Ulus IH, Cansev M, et al. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006;1088:83-92.
24. Carlezon WA, Pliakas AM, Parow AM, et al. Antidepressant-like effects of cytidine in the forced swim test in rats. Biol Psychiatry. 2002;51:882-889.
25. Yoon SJ, Lyoo IK, Haws C, et al. Decreased glutamate/glutamine levels may mediate cytidine's efficacy in treating bipolar depression: a longitudinal proton magnetic resonance spectroscopy study. Neuropsychopharmacology. 2009;34:1810-1818.
26. Carlezon WA, Mague SD, Parow AM, et al. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005;57:343-350.
27. Young RC, Biggs JT, Ziegler VE, et al. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429-435.
28. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
29. Hosmer DW, Lemeshow S. Applied Survival Analysis. New York, NY: Wiley; 1999.
30. Tooze JA, Grunwald GK, Jones RH. Analysis of repeated measures data with clumping at zero. Stat Methods Med Res. 2002;11:341-355.
31. Keck PE Jr, Mintz J, McElroy SL, et al. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry. 2006;60:1020-1022.
32. Cansev M. Uridine and cytidine in the brain: their transport and utilization. Brain Res Rev. 2006;52:389-397.