A pilot, open-label investigation of the efficacy of glucosamine for the treatment of major depression

Introduction: Glucosamine hydrochloride normalizes GABA antagonist- and social defeat-induced behavioral alterations and upregulation of immune response genes in Drosophila and mice, respectively, increases hippocampal neurogenesis in mice, and demonstrates efficacy in murine behavioral models of depression. This suggests that it may have antidepressant potential in humans.

Methods: In an open label, 4-week pilot study, patients (n = 20) diagnosed with mild to moderate, nonpsychotic (unipolar) major depressive episode (DSM-IV) were treated with glucosamine in monotherapy at 1 g/day for 1 week and 2 g/day for 3 more weeks. Patients were assessed at baseline, and at 2- and 4-week follow up using the 21-item Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impression-Improvement (CGI-I) scale, and other measures. An intent-to-treat analysis with last-observation-carried-forward was conducted on the whole sample.

Results: Three patients dropped out before the first follow up; the rest completed the study. HAM-D scores dropped by a third in the sample as a whole; however, only 4 patients (20 %) were considered HAM-D responders (improvement by >50 %) and only 2 patients (10 %) were CGI-I responders (endpoint score of 1 or 2). There were only 2 (10 %) HAM-D remitters (endpoint score <8). There were no serious adverse events and the treatment was well tolerated.

Conclusions: Encouraging preclinical results notwithstanding, glucosamine monotherapy does not appear to be effective against major depression. A more authoritative conclusion would require a randomized controlled trial.