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

Abstract

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.

Figure 1

HAM-D scores over 8 weeks in women receiving SSRI/SNRI augmentation with 5-HTP and creatine. Active treatment provided through week 8; weeks 10 and 12 represent post-treatment follow-up. Error bars represent 95% confidence interval of the mean. Solid horizontal line indicates potential remission score (HAM-D=7). Asterisk (*) represents beginning of statistical significance compared to baseline (Sidak corrected p < 0.05). Dashed vertical line indicates the finish of 8 weeks of treatments.

Figure 2

MADRS scores over 8 weeks in women receiving SSRI/SNRI augmentation with 5-HTP and creatine. Active treatment provided through week 8; weeks 10 and 12 represent post-treatment follow-up. Error bars represent 95% confidence interval of the mean. Solid horizontal line indicates potential remission score (MADRS=10). Asterisk (*) represents beginning of statistical significance compared to baseline (Sidak corrected p < 0.05). Dashed vertical line indicates the finish of 8 weeks of treatments.

Figure 3

BAI scores over 8 weeks in women receiving SSRI/SNRI augmentation with 5-HTP and creatine. Active treatment provided through week 8; weeks 10 and 12 represent post-treatment follow-up. Error bars represent 95% confidence interval of the mean. Solid horizontal line indicates potential remission score (BAI=10). Asterisk (*) represents beginning of statistical significance compared to baseline (Sidak corrected p < 0.05). Dashed vertical line indicates the finish of 8 weeks of treatments.