Vitamin D supplementation in bipolar depression: A double blind placebo controlled trial

J Psychiatr Res. 2017 Dec;95:48-53. doi: 10.1016/j.jpsychires.2017.07.021. Epub 2017 Jul 22.


Objective: Bipolar depression is difficult to treat. Vitamin D supplementation is well tolerated and may improve mood via its neurotransmitter synthesis regulation, nerve growth factor enhancement and antioxidant properties. Vitamin D adjunct reduces unipolar depression, but has not been tried in bipolar depression.

Methods: 18-70yos with DSM IV bipolar depression and Vitamin D deficiency (<30 ng/ml) were randomized in a controlled double blind trial of 5000IU Vitamin D3 po qday supplementation versus placebo for twelve weeks. Change in Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS), medication, and tolerance were assessed q2weeks.

Results: 16 VitD vs 17 placebo subjects did not differ in baseline characteristics (mean = 44 yo, SD = 13), VitD level (19.2 ± 65.8 g/ml vs 19.3 ± 5.5 ng/ml respectively) or mood ratings (MADRS 21.3 ± 6.4 vs 22.8 ± 6.9 respectively). At 12wks, the placebo group VitD levels remained unchanged, while the VitD group levels increased to 28 ng/ml. MADRS score decreased significantly in both placebo (mean = 6.42 (95% CI [2.28 to 10.56]) and VitD groups (mean = 9.54 (95% CI[3.51 to 15.56]) (p = 0.031), but there were no differences between treatment groups (time by treatment interaction estimate: 0.29, t(23) = 0.14, p = 0.89); VitD and placebo groups had similar reductions in YMRS and HAM-A. Vitamin D3 was well tolerated.

Conclusions: In this small study, despite a greater rise in Vitamin D levels in the VitD supplementation group, there was no significant difference reduction in depressive symptoms. However both groups' VitD levels remained deficient. Vitamin D3 supplementation vs placebo did not improve reduction in mood elevation or anxiety symptoms.

Keywords: Bipolar; Depression; Supplement; Vitamin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Aged
  • Anxiety / drug therapy
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / physiopathology
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / pharmacology*
  • Comorbidity
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy*
  • Vitamin D Deficiency / epidemiology
  • Young Adult


  • Cholecalciferol