Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area

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Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area

Sherpa et al., 2025 | Eur Neuropsychopharmacol | Rct

Citation

Sherpa Nima Norbu, De Giorgi Riccardo, ... Dorjee Sangila. Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. Eur Neuropsychopharmacol. 2025-Jan;90:28-35. doi:10.1016/j.euroneuro.2024.10.004

Abstract

Pre-clinical and clinical evidence proposes that creatine monohydrate, an affordable nutraceutical, could be a useful adjunct to conventional antidepressant treatments. In this pilot feasibility and exploratory study, we investigate the 8-week effects of creatine in addition to cognitive-behavioural therapy (CBT) versus placebo plus CBT in depression. For the primary efficacy outcome of change in Patient Health Questionnaire-9 depression score at study endpoint, we used mixed-model repeated measures analysis of covariance. Logistic regressions were employed to assess acceptability (any-cause dropouts), tolerability (dropouts for adverse events), and safety (patients experiencing one or more adverse events). We calculated effect sizes adjusted for age, sex, and baseline depression score. One-hundred participants (50 females, mean age= 30.4 ± 7.4 years) with depression (mean PHQ-9 = 17.6 ± 6.3) were randomised to either creatine+CBT (N = 50) or placebo+CBT (N = 50). At 8 weeks, PHQ-9 scores were lower in both study arms, but significantly more so in participants taking creatine (mean difference= -5.12). Treatment discontinuations due to any cause and to adverse events, and proportion of participants with at least one adverse event were comparable between study arms. This hypothesis-generating trial suggests that creatine could be a useful and safe supplement to CBT for depression. Longer and larger clinical trials are warranted.

Key Findings

Longer and larger clinical trials are warranted.

Outcomes Measured

  • depression

Population

Field Value
Population See abstract
Sample Size 50
Age Range See abstract
Condition depression

MeSH Terms

  • Humans
  • Female
  • Creatine
  • Male
  • Adult
  • Double-Blind Method
  • Pilot Projects
  • Cognitive Behavioral Therapy
  • Feasibility Studies
  • Treatment Outcome
  • Combined Modality Therapy
  • Young Adult
  • Administration, Oral
  • Depression
  • Middle Aged

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial
  • Vertical: creatine-neurological

Provenance

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