Oral Creatine Augmentation to Enhance SSRI Response in Women With MDD


Underlying Mechanism Behind using Creatine:

  • Creatine supplementation is known to increase –> cerebral concentration of phosphocreatine.
  • Increase cerebral creatine –> causes shift in brain creatine kinase activity –> increase production of ATP from phosphocreatine.
  • This increased generation of ATP –> known to contribute to earlier and increased response to antidepressants. 

The following study done by Lyoo et al tested this hypothesis:

  • n= 52 women with MDD
  • Duration= 8-week double-blind placebo-controlled clinical trial
  • Group 1= Escitalopram + creatine (5 g/day, N=25) or
  • Group 2= Escitalopram + placebo (N=27).
  • Dose of Escitalopram= 10 mg/day for the first week and then 20 mg/day for the following 7 weeks.
  • Scale= Hamilton Depression Rating Scale (HAM-D) score.

Results of this study:

  • RESPONSE: Women who received creatine augmentation showed greater improvement of depressive symptoms as early as week 2.
  Week 2 Week 4 Week 8
Creatine (N=25) 32.0% (N=8) 68.0% (N=17) 64.0% (N=16)
Placebo (N=27) 3.7% (N=1) 29.6% (N=8)  63.0% (N=17)


Creatine 13 (52.0%)
Placebo 7 (25.9%) 


  • ADVERSE EVENTS: Similar in both groups- tension headache, nausea and/or vomiting, and sleep difficulties. These are likely related to the use of SSRIs.
Creatine 43.4% (36 events)
Placebo  46.4% (45 events)


The present results suggest that creatine augmentation with the Escitalopram, provides a promising therapeutic approach for MDD in terms of its superior efficacy, relatively good tolerability, minimal side effects, and easy attainability.

Source: Am J Psychiatry. 2012 Sep; 169(9): 937–945.

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Dr. Harvinder Singh, M.D. (Admin)

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