A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression

Abstract

Creatine's effects on brain energy metabolism raise the possibility of developing a new therapeutic strategy in depression focusing on the treatment of metabolic hypoactive brain areas. Previous creatine augmentation studies in patients with major depression showed a beneficial effect. Eighteen patients (14 women) with major depression not responding to previous 3 weeks of antidepressant treatment were enrolled into a pilot, dose finding, 4-week double-blind parallel augmentation study where creatine monohydrate 5 or 10 g daily or placebo was added to ongoing SSRIs/SNRIs/NASA treatment. Rating scales included the Hamilton Depression Rating Scale and the Clinical Global Impression Severity scale. Overall, there was no difference between creatine administered at 5 or 10 g daily and its corresponding placebos. Two female patients on creatine augmentation, but none on the placebo, showed early improvement of more than 50% reduction in Hamilton Depression Rating Scale after 2 weeks of creatine treatment. No clinically relevant side effects were reported. This preliminary study seems to suggest that the strategy using creatine augmentation in major depressive women showing no 'real-life response' to 3 weeks of treatment with SSRIs/SNRIs/NASA treatment is of no advantage compared with placebo. However, such creatine augmentation may still induce a more rapid response in a small subgroup of these female patients.

Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression

“…The authors report the results of what is, to the best of our knowledge, the first 31 P-MRS experimental medicine dose-ranging study of adjunctive CM for female adolescents with SSRI-resistant MDD. While our results diverge with those of a recent dose-ranging study of CM augmentation in adults with TRD (Nemets and Levine 2013 ), the outcome of interest in the present report was PCr measured with translational 31 P-MRS neuroimaging. As found in our previous open-label study (Kondo et al 2011b ), augmentation of SSRI pharmacotherapy with CM was associated with increased frontal lobe PCr.…”

Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle

“…Both doses showed a significant rise in neuronal creatine measured with magnetic resonance imaging (MRI) spectroscopy, confirming that the dosages used are indeed able to increase cerebral creatine content. 135 This study did not find a clinical effect on mood, however it should be noted that, as stated in the title, it was mainly meant as a "dose-finding" study, in other words it was not primarily aimed at finding efficacy of creatine supplementation.…”

“…In a dose‐finding study on 18 patients (14 women) affected by major depression creatine was administered at 3 g/d for 1 week followed by 5 g/d for 3 more weeks or at 5 g/d for 1 week followed by 10 g/d for 3 more weeks. Both doses showed a significant rise in neuronal creatine measured with magnetic resonance imaging (MRI) spectroscopy, confirming that the dosages used are indeed able to increase cerebral creatine content …”

Creatine for the Treatment of Depression

“…The only negative trial of creatine in MDD to our knowledge was conducted by Nemets and Levine [189]. They enrolled 18 subjects (14 women) who had received an SSRI, SNRI, or noradrenergic and specific serotonergic antidepressant (NaSSA) for at least three weeks and who continued to be depressed in a 4-week trial of adjunctive creatine at 5 g or 10 g per day, or placebo.…”