Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis

Context: Serotonergic dysfunction, including reduced central serotonin levels, is associated with different psychiatric syndromes, including depression. As a serotonin precursor, 5-hydroxytryptophan has long been used as a nonpharmacological treatment for depression. Objective: A systematic review and meta-analysis was conducted to determine the antidepressant effects of 5-hydroxytryptophan in depressed patients. Data sources: MEDLINE (via PubMed) and Google Scholar were searched from inception to May 2018. Data extraction: Thirteen investigations were included in the systematic review (using PRISMA guidelines), and 7 in the full meta-analysis (pre-registered on PROSPERO: CRD42018104415). Data analysis: Analyses revealed a depression remission rate of 0.65 (95% confidence interval [CI], 0.55-0.78; remission rate [k]= 13), and this was confirmed by the questionnaire results, which revealed a large Hedges' g (1.11; 95%CI, 0.53-1.69). Methodological variability (in treatment duration, type of depression studied, experimental design, 5-hydroxytryptophan dosage) contributes to heterogeneity in the results (I2 = 76%, s2 = 0.379). In addition, the OHAT (Office of Health Assessment and Translation risk of bias rating) tool suggested that, on the whole, current studies are relatively weak (few include placebo groups). Conclusion: Further trials should overcome these limitations by using placebo-controlled studies that include patients with well-defined depression diagnoses, along with strong characterization of psychological and physiological patient characteristics.