5-HTP

Biological rationale: 5-HTP is the immediate biochemical precursor of serotonin (5-HT). Because many effective OCD treatments (clomipramine, SSRIs) act by increasing serotonergic signalling, supplying more precursor can — in theory — increase brain serotonin and affect OCD symptoms. This is the mechanistic reason researchers tested 5-HTP for obsessive-compulsive symptoms. Cambridge University Press & Assessment

Empirical rationale: Given the serotonin hypothesis of OCD (established by antidepressant response and other studies), researchers have tested serotonin precursors and serotonergic modulators as augmentation or alternative strategies. This is why clinical trials have been done to see if 5-HTP adds benefit. Cambridge University Press & Assessment

What the best clinical trial used (adjunctive setting):

• A 12-week randomized, double-blind, placebo-controlled trial (Yousefzadeh et al., Int Clin Psychopharm, 2020) tested fluoxetine + 5-HTP (100 mg twice daily) versus fluoxetine + placebo in patients with moderate–severe OCD (Y-BOCS > 21). The 5-HTP dose in that trial was 100 mg twice daily (200 mg/day) as an adjunct to fluoxetine. That trial reported greater improvement with the 5-HTP augmentation group than with fluoxetine alone. Ingenta Connect
• If you want the paper: the trial is titled “5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control.” (Int Clin Psychopharm, 2020). Lippincott Journals

Common clinical/regimen notes (outside trials):

• Doses commonly cited in reviews and clinical summaries for mood/anxiety uses range from 50 mg/day up to about 200–300 mg/day, usually split into 2–3 doses; many authors and product monographs recommend starting low and titrating up while monitoring side effects. Clinical trial for OCD used 200 mg/day (100 mg twice daily). WebMD
• If used as augmentation with an SSRI (as in the 2020 trial), do so only under medical supervision. Combining 5-HTP with SSRIs increases serotonergic activity and therefore the risk of serotonin syndrome — but that risk was managed in the supervised clinical trial setting. Do not self-combine 5-HTP with SSRIs or MAOIs without a clinician’s guidance. Ingenta Connect

Practical checklist if someone (with clinician oversight) is considering trialing 5-HTP for OCD:

1. Review current medications (especially SSRIs, SNRIs, MAOIs, triptans, certain analgesics). Stop or adjust only under clinician direction. poison.org
2. Consider 200 mg/day split dosing (100 mg twice daily) only as adjunct — that’s the regimen used in the randomized trial. If a clinician chooses to start lower, common practice is to begin 50–100 mg/day and titrate slowly while watching for side effects. Ingenta Connect
3. Monitor actively for side effects or signs of serotonin excess (see Warnings). Stop and seek urgent care if severe symptoms appear. poison.org.
4. Prefer clinical-grade suppliers and consider brands with independent verification (USP, NSF) to reduce contamination risk. poison.org

Key randomized trial for OCD (adjunctive):

• Yousefzadeh et al., 2020 (Int Clin Psychopharm) — randomized, double-blind, placebo-controlled, 12-week trial of fluoxetine + 5-HTP (100 mg twice daily) vs fluoxetine + placebo in 60 moderate–severe OCD patients. The trial reported that the 5-HTP augmentation group had greater reductions in Y-BOCS scores than the control group. This is the most directly relevant RCT for OCD. Ingenta Connect

Broader evidence context:

• Systematic reviews / Cochrane for 5-HTP in mood disorders: Cochrane and systematic reviews have found some evidence that 5-HTP can reduce depressive symptoms vs placebo, but the evidence base is small, heterogeneous, and older trials had quality limitations. There is far more robust evidence for SSRIs/clomipramine in OCD than for 5-HTP. In short: evidence for mood disorders is mixed/modest; evidence for OCD is limited but includes at least one positive adjunctive RCT. Cochrane Library
• Mechanistic / review papers on serotonin’s role in OCD underpin why serotonergic agents (and by extension, serotonergic precursors) were tested. But mechanistic plausibility does not substitute for multiple, large RCTs. Cambridge University Press & Assessment