Hellem · Journal of dual diagnosis 2015 · Open-label single-arm pilot trial · n=14

Creatine as a Novel Treatment for Depression in Females Using Methamphetamine: A Pilot Study.

Cited 48 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled, single-arm open-label pilot study

PubMed 26457568 · doi:10.1080/15504263.2015.1100471 · record verified 2026-08-26

What was done

Fourteen females with depression and comorbid methamphetamine dependence enrolled in an 8-week open-label trial of 5 g daily creatine monohydrate (11 completed). Depression was assessed using the Hamilton Depression Rating Scale (HAMD), and brain phosphocreatine concentrations were measured using phosphorus magnetic resonance spectroscopy before and after treatment. Secondary outcomes included anxiety symptoms via the Beck Anxiety Inventory (BAI) and methamphetamine use monitored by twice-weekly urine drug screens and self-report.

What was found

A linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores starting at week 2 and continuing through study completion (exact numerical score values were not reported in the abstract). Brain phosphocreatine concentrations increased significantly from baseline (mean = 0.223, SD = 0.013) to post-treatment (mean = 0.233, SD = 0.009; t(9) = 2.905, p < 0.01). Methamphetamine-positive urine drug screens decreased by greater than 50% by week 6. Adverse events possibly related to creatine included gastrointestinal symptoms and muscle cramping.

Why it matters

This pilot study provides preliminary target-engagement and symptom data suggesting creatine monohydrate may warrant further investigation for comorbid depression and methamphetamine dependence in females.

Limits

The study was an open-label trial lacking a control or placebo group, making it impossible to rule out placebo effects or natural symptom fluctuation. The sample size was very small (n = 14 enrolled, n = 11 completed), and the abstract lacks exact point estimates for depression and anxiety score reductions.

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