L-Carnosine combination therapy for major depressive disorder: A randomized, double-blind, placebo-controlled trial

J Affect Disord. 2020 Apr 15;267:131-136. doi: 10.1016/j.jad.2020.02.020. Epub 2020 Feb 7.


Background: Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD).

Methods: Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6.

Results: Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects.

Limitations: Short follow-up period and small population size were two important limitations of this study.

Conclusions: L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation.

Keywords: Glutamate; L-Carnosine; Major depressive disorder (MDD); Randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Carnosine* / therapeutic use
  • Citalopram / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Double-Blind Method
  • Humans
  • Treatment Outcome


  • Antidepressive Agents
  • Citalopram
  • Carnosine