A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression

source extracted confidence: high 2026-04-09
#adult #aged #antidepressive-agents #creatine #major-depressive-disorder

A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression

Nemets et al., 2013 | Int Clin Psychopharmacol | Rct

Citation

Nemets Boris, Levine Joseph. A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression. Int Clin Psychopharmacol. 2013-May;28(3):127-33. doi:10.1097/YIC.0b013e32835ff20f

Abstract

Creatine's effects on brain energy metabolism raise the possibility of developing a new therapeutic strategy in depression focusing on the treatment of metabolic hypoactive brain areas. Previous creatine augmentation studies in patients with major depression showed a beneficial effect. Eighteen patients (14 women) with major depression not responding to previous 3 weeks of antidepressant treatment were enrolled into a pilot, dose finding, 4-week double-blind parallel augmentation study where creatine monohydrate 5 or 10 g daily or placebo was added to ongoing SSRIs/SNRIs/NASA treatment. Rating scales included the Hamilton Depression Rating Scale and the Clinical Global Impression Severity scale. Overall, there was no difference between creatine administered at 5 or 10 g daily and its corresponding placebos. Two female patients on creatine augmentation, but none on the placebo, showed early improvement of more than 50% reduction in Hamilton Depression Rating Scale after 2 weeks of creatine treatment. No clinically relevant side effects were reported. This preliminary study seems to suggest that the strategy using creatine augmentation in major depressive women showing no 'real-life response' to 3 weeks of treatment with SSRIs/SNRIs/NASA treatment is of no advantage compared with placebo. However, such creatine augmentation may still induce a more rapid response in a small subgroup of these female patients.

Key Findings

However, such creatine augmentation may still induce a more rapid response in a small subgroup of these female patients.

Outcomes Measured

  • depression

Population

Field Value
Population major depression showed a
Sample Size See abstract
Age Range See abstract
Condition depression

MeSH Terms

  • Adult
  • Aged
  • Antidepressive Agents
  • Creatine
  • Major Depressive Disorder
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors
  • Treatment Outcome

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
  • Vertical: creatine-neurological

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09