Important adverse events to be evaluated in antidepressant trials and meta-analyses in depression: a large international preference study including patients and healthcare professionals

Journal article

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

Authors: Chevance, A; Tomlinson, A; Ravaud, P; Touboul, S; Henshall, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ
• Journal: BMJ Mental Health
• Volume: 25
• Issue: e1
• Pages: e41-e48
• Publication date: 2022-07-29
• Acceptance date: 2022-06-15
• DOI: 10.1136/ebmental-2021-300418
• ISSN: 1362-0347
• Language: English
• Keywords: Anxiety; Psychology; Antidepressant; Meta-analysis; Psychiatry; Depression (economics); Clinical psychology; Medicine; Clinical trial; Health care; Preference; Adverse effect; Internal medicine; Political science; Health professionals