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

J Dual Diagn. 2015;11(3-4):189-202. doi: 10.1080/15504263.2015.1100471.


Objective: Depression among methamphetamine users is more prevalent in females than males, but gender-specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment-resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users.

Methods: Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8-week open label trial of 5 g of daily creatine monohydrate and of these 14, 11 females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use.

Results: The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t (9) = 2.905, p <.01, suggesting that creatine increased phosphocreatine levels. Also, a reduction in methamphetamine positive urine drug screens of greater than 50% was observed by week 6. Finally, creatine was well tolerated and adverse events that were related to gastrointestinal symptoms and muscle cramping were determined as possibly related to creatine.

Conclusions: The current study suggests that creatine treatment may be a promising therapeutic approach for females with depression and comorbid methamphetamine dependence. This study is registered on (NCT01514630).

Keywords: co-occurring; comorbidity; depression; methamphetamine dependence; neuroimaging; substance use disorders; women's health.

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / complications*
  • Antidepressive Agents / therapeutic use*
  • Brain / metabolism
  • Creatine / therapeutic use*
  • Depressive Disorder / complications
  • Depressive Disorder / drug therapy*
  • Diagnosis, Dual (Psychiatry)
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Methamphetamine*
  • Middle Aged
  • Phosphocreatine / metabolism
  • Pilot Projects
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents
  • Phosphocreatine
  • Methamphetamine
  • Creatine

Associated data