Tryptophan (L-tryptophan, antidepressant adjunct [prescription product]) (United States: Not available): Drug information

(For additional information see "Tryptophan (L-tryptophan, antidepressant adjunct [prescription product]) (United States: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: Canada

APO-Tryptophan;
DOM-Tryptophan;
TEVA-Tryptophan;
Tryptan

Dosing: Adult

Depressive disorders

Depressive disorders: Note: Use as an adjunct to antidepressant therapy.

Oral: 8 to 12/g day in 3 to 4 divided doses.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Gastrointestinal: Anorexia, nausea, xerostomia

Hypersensitivity: Hypersensitivity reaction (including edema, myalgia)

Nervous system: Disinhibition (sexual), dizziness, drowsiness, headache, serotonin syndrome

Contraindications

Hypersensitivity to tryptophan or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Cataracts: Patients may be more susceptible to cataract formation (especially if exposed to UV light) due to raised lenticular tryptophan and kynurenine concentrations.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Hypersensitivity reactions: Hypersensitivity reactions (eg, edema, myalgia, pruritus, rash, urticaria, wheezing) have been reported.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome has rarely occurred with concomitant use of tryptophan and serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors). Monitor patients closely for signs of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

Disease-related concerns:

• Achlorhydria: Patients with achlorhydria may be more susceptible to emphysema and pulmonary edema.

• Diabetes: Use with caution in patients with a history of diabetes.

• Protein deprived: Amino acid imbalance may occur in patients who are protein deprived and treated with tryptophan.

Generic Equivalent Available: US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Tryptan: 500 mg

Generic: 500 mg

Tablet, Oral:

Tryptan: 500 mg, 1 g

Generic: 500 mg, 1 g

Administration: Adult

Oral: Administer with meals or snacks.

Use: Labeled Indications

Note: Not approved in the United States.

Depressive disorders: Adjunct to antidepressant therapy in the management of patients with depressive disorders (eg, bipolar affective disorder).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination

Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Diamorphine: May enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid combination

Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Gepirone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Levomethadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Linezolid: May enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid combination

Lithium: May enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Methadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Methylene Blue: Tryptophan may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): May enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Type B): May enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Risk X: Avoid combination

Nefazodone: May enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy

Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: Serotonergic Agents (High Risk, Miscellaneous) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonergic Non-Opioid CNS Depressants: Serotonergic Agents (High Risk, Miscellaneous) may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Pregnancy Considerations

Endogenous tryptophan crosses the placenta (Kamimura 1991).

Tryptophan is an essential amino acid. Enzymes in the placenta regulate endogenous tryptophan metabolism and fetal exposure via the serotonin and kynurenine pathways. Endogenous tryptophan and its metabolites are needed for placentation, fetal development, and immune regulation during pregnancy. The kynurenine pathway plays an essential role in preventing the maternal immune system from rejecting the developing fetus. Neonatal concentrations decrease 24 hours after birth (Kamimura 1991; Karahoda 2020).

Maternal concentrations of endogenous tryptophan and metabolites vary as pregnancy progresses (Duan 2018; Teshigawara 2019). Fluctuations in endogenous maternal tryptophan concentrations may impact metabolism and influence the development of postpartum depression (Duan 2018; Trujillo 2018). Information related to tryptophan supplementation to prevent postpartum depression in limited (Dowlati 2017; Dowlati 2021).

Breastfeeding Considerations

Tryptophan is present in breast milk (Dowlati 2015; Kamimura 1991).

Concentrations of endogenous tryptophan (total and unbound/free) are highest in the colostrum. Concentrations in breast milk decrease from 5 to 7 days postpartum and decline over 30 days after delivery (Kamimura 1991; Zanardo 1989).

Tryptophan breast milk concentrations may increase following supplementation. Breastfeeding patients 2 to 24 months postpartum were administered a single oral dose of tryptophan 2 g (n=6) or 4 g (n=6). Breast milk was sampled prior to and for 6 hours after the dose. Breast milk concentrations of total tryptophan were not significantly increased above baseline. Concentrations of unbound/free tryptophan showed a dose-dependent increase, peaking 2 hours after the dose, then decreasing over 6 hours. Free tryptophan concentrations in 12 infant formulas were also measured. Two formulas had free tryptophan concentrations below the limit of detection. Free concentrations of tryptophan in the remaining infant formulas were similar to or greater than the concentrations of unbound/free tryptophan measured in breast milk following the single oral dose (Dowlati 2015).

Mechanism of Action

An essential amino acid which is a precursor to serotonin

Pharmacokinetics (Adult Data Unless Noted)

Metabolism: ~98% is metabolized into nicotinic acid and only a small amount into serotonin via the intermediary stage of 5-hydroxy-tryptophan. CNS serotonin is metabolized by monoamine oxidase to 5-HIAA.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AT) Austria: Kalma;
(AU) Australia: L-tryptophan | Nature's own natural high potency l-tryptoph;
(BR) Brazil: Ansiocalm | Kmill | L triptofano pure | L trofan | L-tryptophan | Levita | Marazen | Sereben | Serenoa | Serezen | Sunfood L triptofano | Tripto zen | Triptofan | Triptofano | Triptofano dreams | Up vitam triptofan;
(DE) Germany: Apologo L tryptophan | Ardeydorm | Ardeytropin | Encormed l tryptophan | Kalma | L tryptophan | L-tryptophan | My Vegan Energy L Tryptophan Base;
(GB) United Kingdom: Optimax | Optimax wv | Pacitron;
(IE) Ireland: L-tryptophan;
(JP) Japan: Eltrip;
(LT) Lithuania: L-tryptophan | Swanson l tryptophan;
(LV) Latvia: L-tryptophan;
(NO) Norway: L tryptophan | L-tryptophan;
(PY) Paraguay: The vitamin shoppe l tryptophan;
(TR) Turkey: Venatura 5 htp;
(UY) Uruguay: Geriterona

Dowlati Y, Meyer JH. Promising leads and pitfalls: a review of dietary supplements and hormone treatments to prevent postpartum blues and postpartum depression. Arch Womens Ment Health. 2021;24(3):381-389. doi:10.1007/s00737-020-01091-3 [PubMed 33205315]
Dowlati Y, Ravindran AV, Maheux M, Steiner M, Stewart DE, Meyer JH. No effect of oral L-tryptophan or alpha-lactalbumin on total tryptophan levels in breast milk. Eur Neuropsychopharmacol. 2015;25(6):779-787. doi:10.1016/j.euroneuro.2015.03.005 [PubMed 25823693]
Dowlati Y, Ravindran AV, Segal ZV, Stewart DE, Steiner M, Meyer JH. Selective dietary supplementation in early postpartum is associated with high resilience against depressed mood. Proc Natl Acad Sci U S A. 2017;114(13):3509-3514. doi:10.1073/pnas.1611965114 [PubMed 28289215]
Duan KM, Ma JH, Wang SY, Huang Z, Zhou Y, Yu H. The role of tryptophan metabolism in postpartum depression. Metab Brain Dis. 2018;33(3):647-660. doi:10.1007/s11011-017-0178-y [PubMed 29307018]
Kamimura S, Eguchi K, Sekiba K. Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period. Acta Med Okayama. 1991;45(2):101-106. doi:10.18926/AMO/32183 [PubMed 1867111]
Karahoda R, Abad C, Horackova H, et al. Dynamics of tryptophan metabolic pathways in human placenta and placental-derived cells: effect of gestation age and trophoblast differentiation. Front Cell Dev Biol. 2020;8:574034. doi:10.3389/fcell.2020.574034 [PubMed 33072756]
Teshigawara T, Mouri A, Kubo H, et al. Changes in tryptophan metabolism during pregnancy and postpartum periods: potential involvement in postpartum depressive symptoms. J Affect Disord. 2019;255:168-176. doi:10.1016/j.jad.2019.05.028 [PubMed 31158779]
Trujillo J, Vieira MC, Lepsch J, et al. A systematic review of the associations between maternal nutritional biomarkers and depression and/or anxiety during pregnancy and postpartum. J Affect Disord. 2018;232:185-203. doi:10.1016/j.jad.2018.02.004 [PubMed 29494902]
Tryptan (tryptophan) [product monograph]. Laval, Quebec, Canada: Bausch Health Canada Inc; June 2021.
Zanardo V, Bacolla G, Biasiolo M, Allegri G. Free and bound tryptophan in human milk during early lactation. Biol Neonate. 1989;56(1):57-59. doi:10.1159/000242987 [PubMed 2758083]

Topic 132504 Version 17.0

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Tryptophan (L-tryptophan, antidepressant adjunct [prescription product]) (United States: Not available): Drug information