5-hydroxytryptophan (5-HTP)

5-HTP is sold as a «natural sleep aid» on the «5-HTP → serotonin → melatonin» hypothesis. Several small RCTs showed mild improvement in sleep latency. AASM 2021 and SES 2016 list CBT-I first-line for chronic insomnia; 5-HTP is in no international sleep guideline. If 5-HTP was recommended for chronic insomnia instead of CBT-I or workup for sleep apnoea and restless legs syndrome, consider seeking a second opinion. It is also important to check whether the patient takes serotonergic drugs (SSRIs, tramadol, triptans) – serotonin syndrome risk.

5-HTP was historically considered for migraine prophylaxis on the serotonin hypothesis. Several small 1980s RCTs showed attack frequency reduction comparable to methysergide (a drug withdrawn for retroperitoneal fibrosis). No modern evidence base: AAN 2012 and SEN 2020 list propranolol, metoprolol, topiramate, candesartan or anti-CGRP monoclonals (severe forms) as first-line for migraine prophylaxis. 5-HTP is in no international guideline. If 5-HTP was recommended for migraine, especially with triptans (serotonin syndrome risk), consider seeking a second opinion.

5-HTP is widely sold as a «natural antidepressant» promising a «safe SSRI alternative». Evidence base is weak: Cochrane 2002 (Shaw) reviewed 108 studies, of which only 2 RCTs met quality criteria – 64 patients total, ambiguous results. No large modern RCT has confirmed clinically meaningful 5-HTP efficacy in depression. NICE 2022 and SEP 2014 list CBT and SSRIs first-line for mild-to-moderate depression; 5-HTP is not included. Main risk: self-combination with an antidepressant or tramadol – serotonin syndrome (tachycardia, hyperthermia, myoclonus, rigidity, confusion). If 5-HTP was recommended for depression instead of a psychiatric consultation, consider seeking a second opinion.

5-HTP is sold as a «natural anxiolytic» on the hypothesis: serotonin regulates anxiety; raising brain serotonin reduces anxiety. Logic is correct (basis of SSRIs), but direct transfer to a 5-HTP supplement fails: oral 5-HTP is significantly converted to serotonin in the periphery (platelets, GI tract), causing nausea and tachycardia, while only a fraction reaches the CNS. NICE 2022 and SEP 2014 list SSRIs and CBT first-line for anxiety disorders. Main risk: combination with SSRIs, tramadol or triptans – serotonin syndrome. If 5-HTP was recommended for GAD or panic attacks instead of a psychiatric consultation, consider seeking a second opinion.