5-Hydroxytryptophan (5-HTP)
  Uses of this Supplement
Headache, Migraine
  Supplements with Similar Uses
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  Drugs that Interact
Carbidopa-containing Medications
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
  Supplements with Similar Side Effects
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Look Up > Supplements > 5-Hydroxytryptophan (5-HTP) > Interactions
Interactions with 5-Hydroxytryptophan (5-HTP)

A case of scleroderma-like illness has been reported in a patient taking L-5-hydroxytryptophan and carbidopa (Joly et al. 1991). An earlier case reported a similar interaction between carbidopa and 5-HTP (Sternberg et al. 1980). This interaction may be due to an alteration in tryptophan metabolism (Joly et al. 1991).

Monoamine Oxidase Inhibitors (MAOIs); Selective Serotonin Reuptake Inhibitors (SSRIs); Sumatriptan

Concomitant use of sumatriptan, SSRIs, and monoamine oxidase inhibitors (MAOIs) is contraindicated due to increased risk for developing serotonin syndrome (Gardner and Lynd 1998; Hines Burnham et al 2000; Joffe and Sokolov 1997). Serotonin syndrome is characterized by mental status changes, rigidity, hyperthermia, rapidly fluctuating vital signs, and possibly coma. Sumatriptan could theoretically interact with 5-HTP by enhancing serotonergic effects.


Tramadol inhibits serotonin uptake and may interact with 5-HTP supplements. A serotonin-like syndrome has been reported in patients taking tramadol with other medications that increase serotonin levels in the central nervous system (Hernandez et al. 1995; Mason and Blackburn 1997; Spiller et al. 1997).

Trazodone; Venlafaxine

Antidepressants that inhibit serotonin reuptake may interact with 5-HTP supplements by enhancing serotonergic effects, causing symptoms related to central and peripheral toxicity. A serotonin-like syndrome has been reported in patients taking trazodone with other medications that increase serotonin levels in the central nervous system (Bodner et al. 1995; George and Godleski 1996; Nisijima et al. 1996; Reeves and Bullen 1995). Serotonin syndrome has also been reported in patients taking venlafaxine with other medications that increase serotonin levels (Bhatara et al. 1998; Diamond et al. 1998; Perry 2000).


There are several case reports of patients experiencing prolonged hallucinations while taking zolpidem with SSRIs (Elko et al. 1998; Toner et al. 2000). The mechanism for this interaction is not known. Because 5-HTP increases serotonin levels in the brain, it could interact with zolpidem, although no reports of such an interaction are known to have been identified in the literature to date.


Bhatara VS, Magnus RD, Paul KL, et al. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechansims. Ann Pharmacother. 1998;32(4):432-436.

Bodner RA,Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurol. 1995;45(2):219-223.

Diamond S, Pepper BJ, Diamond MI, et al. Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports. Neurol. 1998;51(1):274-276.

Elko CJ, Burgess JL, Robertson WO. Zolpidem--associated hallucinations and serotonin reuptake inhibition: a possible interaction. J Toxicol Clin Toxicol. 1998;36(3):195-203.

Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32(1):33-38.

George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry. 1996 Mar;39(5):384-385.

Hernandez AF, Montero MN, Pla A, Villanueva E, et al. Fatal moclobemide overdose or death caused by serotonin syndrome? J Forensic Sci. 1995;40(1):128-130.

Hines Burnham, et al, eds. Drug Facts and Comparisons 2000. 55th ed. St. Louis, MO:Facts and Comparisons; 2000.

Joffe RT, Sokolov ST. Co-adminstration of fluoxetine and sumatriptan: the Canadian experience. Acta Psychiatr Scand. 1997;95(6):551-552.

Joly P, Lampert A, Thomine E, Lauret P. Development of pseudobullous morphea and sclero-derma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. J Am Acad Dermatol. 1991;25(2):332-333.

Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother. 1997;31(2):175-177.

Nisijima K, Shimizu M, Abe T, Ishijuro T. A case of serotonin syndrome induced by concomitant treatment with low-dose trazodone and amitriptyline and lithium. Int Clin Psychopharmacol. 1996 Dec;11(4):289-290.

Perry NK. Venlafaxine-induced serotonin syndrome with relapse following amitripyline. Postgrad Med J. 2000;76(894):254.

Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosom. 1995 Mar-Apr;36(2):159-160.

Spiller HA, Gorman SE, Villalobos D, et al. Prospective multicenter evaluation of tramadol exposure. J Toxicol Clin Toxicol. 1997;35(4):361-364.

Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. New Eng J Med. 1980;303:782-787.

Toner LC, Tsambiras BM, Catalano G, et al. Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol. 2000;23(1):54-58.

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