L-Tryptophan and 5-Hydroxytryptophan in Mental Health Care

Depressed mood

The amino acids 5-hydroxytryptophan (5-HTP) and l-tryptophan are precursors of serotonin. 5-HTP is generally recommended over l-tryptophan because it crosses the blood-brain barrier at a higher rate, is converted into serotonin more efficiently than l-tryptophan, and has a more pronounced antidepressant effect. A systematic review of RCTs on 5-HTP or l-tryptophan in depressed mood identified 108 studies, but design problems and small study size limited analysis of findings to only two studies (N=64) that met inclusion criteria. On the basis of those limited findings, the reviewers concluded that 5-HTP is probably more effective than placebo at doses of 100 to 300 mg per day for moderately depressed mood. Sixty-three depressed patients randomized to fluvoxamine 150 mg per day or 5-HTP 300 mg per day reported equivalent improvements in mood. In an open study, almost half of treatment-refractory depressed patients (N=100) responded to 5-HTP (up to 600 mg per day) in combination with 150 mg per day of carbidopa after several weeks of treatment. Case reports show that some treatment-refractory patients improve when 300 mg per day of 5-HTP is combined with carbidopa (a peripheral monoamine oxidase inhibitor (MAOI), tricyclic antidepressants, MAOIs, or serotonin selective reuptake inhibitors (SSRI).

Preliminary findings support that combining 1 to 3 g per day of l-tryptophan and early-morning bright light exposure is more efficacious than either treatment alone in patients diagnosed with seasonal affective disorder. In a double-blind study, 58 percent of generally anxious patients (N=79) randomized to 3 g per day of l-tryptophan reported significantly greater reductions in baseline anxiety compared to placebo

Anxiety

Findings of placebo-controlled trials show consistent beneficial effects of 5-HTP for generalized anxiety and panic disorder. Patients diagnosed with generalized anxiety disorder randomized to 5-HTP with carbidopa versus clomipramine reported equivalent and significant reductions in generalized anxiety. 5-HTP at 50 to 100 mg thrice daily is well tolerated when used at recommended doses alone or in combination with conventional antianxiety agents.

Insomnia

l-Tryptophan, 1 g, at bedtime reduces time to sleep onset in mild situational insomnia, and doses up to 15 g at bedtime may be necessary for severe insomnia. Case reports suggest that nighttime use of 5-HTP at 300 to 600 mg may improve mild to moderate insomnia and lessen sleep disturbances related to obstructive sleep apnea and narcolepsy. Combining 2 g of l-tryptophan with 20 mg per day of fluoxetine resulted in more rapid response and improved sleep quality in depressed patients complaining of chronic insomnia. No cases of serotonin syndrome or other serious adverse effects were reported with these doses.

Side effects and safety issues

Transient mild adverse effects reported with l-tryptophan and 5-HTP include nausea, constipation, dry mouth, blurred vision, drowsiness, and decreased libido. l-Tryptophan is typically taken at bedtime because of its sedating properties and is dosed between 1.5 and 5.0 g, depending on therapeutic response. 5-HTP is also moderately sedating and doses greater than 100 mg should be taken at bedtime. Cases of serious serotonin syndrome have been reported when MAOIs are combined with l-tryptophan, including orthostatic hypotension, hyperreflexia, diaphoresis, and delirium. Fifteen hundred cases of eosinophilia-myalgia syndrome (EMS) and 37 deaths in patients taking l-tryptophan were reported in the late 1980s and early 1990s. All cases were traced to contaminants in a single batch of one over-the-counter brand of l-tryptophan. The manufacturing problem that resulted in the contaminated batch was identified and corrected, and there have been no subsequent reports of EMS associated with l-tryptophan.