Creatine monohydrate in resistant depression: a preliminary study

Bipolar Disord. 2007 Nov;9(7):754-8. doi: 10.1111/j.1399-5618.2007.00532.x.


Objectives: Creatine plays a pivotal role in brain energy homeostasis, and altered cerebral energy metabolism may be involved in the pathophysiology of depression. Oral creatine supplementation may modify brain high-energy phosphate metabolism in depressed subjects.

Methods: Eight unipolar and two bipolar patients with treatment-resistant depression were treated for four weeks with 3-5 g/day of creatine monohydrate in an open add-on design. Outcome measures were the Hamilton Depression Rating Scale, Hamilton Anxiety Scale, and Clinical Global Impression scores, recorded at baseline and at weeks 1, 2, 3 and 4.

Results: One patient improved considerably after one week and withdrew. Both bipolar patients developed hypomania/mania. For the remaining seven patients, all scale scores significantly improved. Adverse reactions were mild and transitory.

Conclusions: This small, preliminary, open study of creatine monohydrate suggests a beneficial effect of creatine augmentation in unipolar depression, but possible precipitation of a manic switch in bipolar depression.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / chemically induced
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / metabolism*
  • Bipolar Disorder / psychology
  • Brain / drug effects
  • Brain / metabolism
  • Creatine / adverse effects
  • Creatine / pharmacology
  • Creatine / therapeutic use*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Resistance
  • Drug Therapy, Combination
  • Energy Metabolism / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphates / metabolism
  • Psychiatric Status Rating Scales
  • Treatment Outcome


  • Antidepressive Agents
  • Phosphates
  • Creatine