Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor– or Serotonin-Norepinephrine Reuptake Inhibitor–Resistant Depression in Adult Women

Kious, Brent M. MD, PhD*; Sabic, Hana BS; Sung, Young-Hoon MD*†; Kondo, Douglas G. MD*†; Renshaw, Perry MD, PhD*†‡

Journal of Clinical Psychopharmacology: October 2017 - Volume 37 - Issue 5 - p 578–583
doi: 10.1097/JCP.0000000000000754
Original Contributions

Purpose Many women with major depressive disorder (MDD) respond inadequately to standard treatments. Augmentation of conventional antidepressants with creatine monohydrate and 5-hydroxytryptophan (5-HTP) could correct deficits in serotonin production and brain bioenergetics associated with depression in women, yielding synergistic benefit. We describe an open-label study of 5-HTP and creatine augmentation in women with MDD who had failed selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) monotherapy.

Methods Fifteen women who were adequately adherent to an SSRI or SNRI and currently experiencing MDD, with a 17-item Hamilton Depression Rating Scale (HAM-D) score of 16 or higher, were treated with 5 g of creatine monohydrate daily and 100 mg of 5-HTP twice daily for 8 weeks, with 4 weeks of posttreatment follow-up. The primary outcome was change in mean HAM-D scores.

Results Mean HAM-D scores declined from 18.9 (SD, 2.5) at pretreatment visits to 7.5 (SD, 4.4) (P < 0.00001), a decrease of 60%. Participants did not experience any serious treatment-related adverse events.

Conclusions Combination treatment with creatine and 5-HTP may represent an effective augmentation strategy for women with SSRI- or SNRI-resistant depression. Given the limitations of this small, open-label trial, future study in randomized, placebo-controlled trials is warranted.

From the *Department of Psychiatry and †Brain Institute, University of Utah; and ‡Veterans Integrated Service Network 19 Mental Illness Research Education Clinical, Centers of Excellence, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.

Received February 12, 2017; accepted after revision May 12, 2017.

Reprints: Brent M. Kious, MD, PhD, Department of Psychiatry, University of Utah, 501 Chipeta Way, Salt Lake City, UT 84108 (e-mail:

This work was supported by a grant from the R. Harold Burton Foundation (Salt Lake City, UT) and the Utah Science, Technology, and Research Initiative (Salt Lake City, UT).

Trial Registration: identifier NCT02356107.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.