5-HTP

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References

Auffranc JC, Berbis P, Fabre JF, Garnier JP, Privat Y. Sclerodermiform and poikilodermal syndrome observed during treatment with carbidopa and 5-hydroxytryptophan. Ann Dermatol Venereol. 1985;112(9):691-692. [Article in French]

Baker GB; Fang J; Sinha S; Coutts RT. Metabolic drug interactions with selective serotonin reuptake inhibitor (SSRI) antidepressants. Neurosci Biobehav Rev 1998 Mar;22(2):325-333.
Abstract: The selective serotonin reuptake inhibitor (SSRI) antidepressants have become an important component of the therapeutic armamentarium in psychiatry and have attracted a great deal of public attention. Another interesting aspect of the SSRIs is their interaction with various isozymes of the cytochrome P450 (CYP) system which are responsible for metabolism of numerous drugs. This effect on the CYP isozymes has drawn attention to the importance of metabolic drug-drug interactions when dealing with drugs used to treat psychiatric disorders. Such interactions are of great relevance since psychiatry patients are frequently treated with multiple drugs and often these drugs undergo extensive biotransformation to metabolites which contribute to therapeutic and/or adverse effects. The present review deals with various aspects of metabolism mediated by CYP isozymes, particularly as they relate to pharmacokinetic interactions between the SSRIs and other drugs which are coadministered with them.

Barr LC, Heninger GR, Goodman W, Charney DS, Price LH. Effects of fluoxetine administration on mood response to tryptophan depletion in healthy subjects. Biol Psychiatry. 1997 May 1;41(9):949-954.
Abstract: Short-term reduction in plasma tryptophan (tryptophan depletion) produces a relapse of depressive symptoms in 60% of previously depressed patients recently recovered with serotonin reuptake inhibitor treatment. Tryptophan depletion does not consistently increase depressive symptoms in unmedicated depressed patients or in depressed patients whose symptoms are remitted with a norepinephrine reuptake inhibitor. These data suggest that serotonin reuptake inhibitor treatment itself may confer vulnerability to the development of depressive symptoms during tryptophan depletion. In order to further investigate this possibility, six healthy individuals underwent double-blind placebo-controlled tryptophan depletion before and following six weeks of treatment with fluoxetine 20 mg/day. No increased vulnerability to the mood-lowering effects of tryptophan depletion occurred as a result of fluoxetine treatment. Additionally, fluoxetine treatment itself was not associated with changes in mood or quality of life in these healthy volunteers. These data indicate that serotonin reuptake inhibitor treatment alone does not produce the depressive effects of tryptophan depletion that are observed in serotonin reuptake inhibitor-treated depressed and obsessive compulsive disorder patients.

Birmaher B, Kaufman J, Brent DA, Dahl RE, Perel JM, al-Shabbout M, Nelson B, Stull S, Rao U, Waterman GS, Williamson DE, Ryan ND. Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder. Arch Gen Psychiatry. 1997 Dec;54(12):1113-1119.
Abstract: BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli F.  Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. 1992 Nov;56(5):863-867.
Abstract: Previous observations have shown that oral administration of 5-hydroxytryptophan (5-HTP) without dietary prescriptions causes anorexia, decreased food intake, and weight loss in obese subjects. To confirm these data over a longer period of observation and to verify whether adherence to dietary restriction could be improved by 5-HTP, 20 obese patients were randomly assigned to receive either 5-HTP (900 mg/d) or a placebo. The study was double-blinded and was for two consecutive 6-wk periods. No diet was prescribed during the first period, a 5040-kJ/d diet was recommended for the second. Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found. These findings together with the good tolerance observed suggest that 5-HTP may be safely used to treat obesity.

Cangiano C, Ceci F, Cairella M, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Rossi-Fanelli F. Effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects. Adv Exp Med Biol. 1991;294:591-593.

Ceci F, Cangiano C, Cairella M, Cascino A, Del Ben M, Muscaritoli M, Sibilia L, Rossi Fanelli F. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76(2):109-117.
Abstract: Nineteen obese female subjects with body mass index ranging between 30 and 40 were included in a double-blind crossover study aimed at evaluating the effects of oral 5-hydroxytryptophan administration on feeding behavior, mood state and weight loss. Either 5-hydroxytryptophan (8 mg/kg/day) or placebo was administered for five weeks during which patients were not prescribed any dietary restrictions. Feeding behavior was investigated by means of a questionnaire designed to establish the onset of anorexia and related symptoms. Food intake was evaluated using a three-day diet diary. BDI, SI, STAI-T, and STAI-S were used to assess mood state. The administration of 5-hydroxytryptophan resulted in no changes in mood state but promoted typical anorexia-related symptoms, decreased food intake and weight loss during the period of observation.

Chan BS, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust 1998 Nov 16;169(10):523-525.
Abstract: We describe six patients diagnosed with serotonin syndrome after exposure to drugs with serotonergic activity. Drug interactions occurred as a result of a combination of tricyclic antidepressants, selective serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors or monoamine oxidase inhibitors. Management included supportive care and the use of non-specific serotonin antagonists (cyproheptadine, benzodiazepines and chlorpromazine). All patients made uneventful recoveries.

den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990 Mar;31(3):267-278.
Abstract: L-5-Hydroxytryptophan (5HTP) was administered to 20 patients suffering from panic disorder and to 20 healthy controls. Subjects received 60 mg 5HTP in 300 ml saline solution. Before, during, and up to 2 hours after 5HTP administration, symptoms of anxiety and depression were assessed. In addition, plasma 5HTP, 3-methoxy-4-hydroxyethylglycol (MHPG), cortisol, beta-endorphin, and melatonin levels were measured at several time points, and the kinetics of 5-hydroxytryptamine (5HT) in blood platelets were measured. During and after the infusion of 5HTP, none of the patients showed an increase in anxiety or depressive symptoms, despite the presence of severe side effects. Some patients even experienced the 5HTP infusion as a relief. In contrast to the patients, nine control subjects reported depressed mood, although no increases in anxiety were noted. In both patients and controls, the 5HTP infusion led to substantial increases in plasma cortisol and beta-endorphin levels, while the plasma MHPG level was unchanged. Plasma melatonin increased significantly after 5HTP administration, suggesting that increasing 5HT availability in man might affect melatonin synthesis. The results of this study are at odds with the hypothesis that there is a supersensitivity of 5HT2 receptors in panic disorder.

Fuller RW. Biochemical pharmacology of the serotonin system. Adv Neurol. 1986;43:469-480. (Review)

Growdon JH, Young RR, Shahani BT. L-5-hydroxytryptophan in treatment of several different syndromes in which myoclonus is prominent. Neurology 1976 Dec;26(12):1135-1140.
Abstract: The serotonin precursor L-5-hydroxytryptophan is useful therapy for patients with posthypoxic intention myoclonus. L-5-hydroxytryptophan plus carbidopa was administered to eight patients with this disorder or other syndromes in which myoclonus is prominent. This treatment (1) decreased the frequency of occurrence and amplitude of intention myoclonus in two patients with posthypoxic intention myoclonus and in one with idiopathic myoclonus, (2) had no effect in one patient with congenital encephalopathy and myoclonus, and (3) increased the frequency of occurrence and amplitude of myoclonus in two patients with lipid storage disease, one with myoclonic epilepsy, and in an additional patient with idiopathic myoclonus. Therefore, L-5-hydroxytryptophan does not effect improvement in all forms of myoclonus; it should be given with caution because it produces a high incidence of side effects. A patient's response to L-5-hydroxytryptophan therapy may be important in a diagnostic classification of myoclonic syndromes based on differences in indoleamine neurotransmitter function.

Irwin MR, Marder SR, Fuentenebro F, Yuwiler A. L-5-hydroxytryptophan attenuates positive psychotic symptoms induced by D-amphetamine. Psychiatry Res. 1987 Dec;22(4):283-289.
Abstract: Brain serotonin has been hypothesized to be involved in the modulation of psychotic symptoms in at least some forms of schizophrenia. We examined the effects of the serotonin precursor L-5-hydroxytryptophan (5HTP) on D-amphetamine induction of acute psychotic symptoms in schizophrenic patients. Preadministration with 5HTP significantly antagonized amphetamine-elicited elevations in thought disturbance, activation, and hallucinations.

Joly P, Lampert A, Thromine E, Lauret P. Development of pseudobullous morphea and scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. J Am Acad Dermatol. 1991 Aug;25(2 Pt 1):332-333.

Lado-Abeal J, Grana M, Rey C, Cabezas-Cerrato J. L-5-hydroxytryptophan does not stimulate LH secretion directly from the pituitary in patients with gonadotrophin releasing hormone deficiency. Clin Endocrinol (Oxf). 1998 Aug;49(2):203-207.
Abstract: OBJECTIVE: There is abundant histological and physiological evidence that serotonin plays a role in the regulation of LH secretion in rats. Studies in human subjects have been few, but their results include the finding that pulsatile administration of L-5-hydroxytryptophan (5-HTP, the immediate precursor of serotonin) amplifies LH secretion in women in the medium-late follicular phase, and that this effect is not due to 5-HTP directly inducing LH secretion by the pituitary. We have investigated whether 5-HTP amplifies LH secretion by enhancing the response of the pituitary to GnRH. PATIENTS: Seven patients aged 20-40 years with hypogonadotrophic hypogonadism (HH) of hypothalamic origin (3 men with Kallmann's syndrome, 2 women without anosmia and with GH deficiency, and 2 women with anorexia nervosa). DESIGN: To prime the pituitary, subcutaneous pulsatile GnRH was administered for 7 days at the rate of one 5-20 micrograms pulse every 90 min. The day before the investigation, this regimen was replaced by 1.5-3 micrograms intravenous pulses at the same frequency. On the day of the investigation, 3 ml blood samples were taken every 10 min from 0850 to 19:00 hours. After the first two samples, the intravenous GnRH pulse frequency was increased to one per hour and was maintained at this level throughout the rest of the study. The first 4 h of the study acted as a control phase allowing determination of the pituitary response to GnRH. At 1300 h, 75 mg of the aromatic-L-amino-acid decarboxylase inhibitor carbidopa was administered orally; carbidopa does not cross the blood-brain barrier, and prevents peripheral conversion of 5-HTP to serotonin. At 1600 h, another 75 mg dose of carbidopa was administered, and administration of 8-20 mg pulses of 5-HTP at a rate of one pulse per hour was begun. MEASUREMENTS: LH was determined in triplicate by an immunoradiometric assay (IRMA), and LH pulses identified by means of a program developed in our laboratory. RESULTS: When pulsatile administration of GnRH was accompanied by administration of carbidopa and 5-HTP, LH pulse amplitude (2.32 +/- 0.71 IU/I) did not differ significantly from its value in either the GnRH+ carbidopa phase (2.58 +/- 1.12 IU/I) or the unaccompanied GnRH phase (2.77 +/- 1.76 IU/I). CONCLUSIONS: L-5-hydroxytryptophan-induced amplification of LH secretion in humans is not due to enhancement of the pituitary response to GnRH. The effect of L-5-hydroxytryptophan must therefore be due to its action on the hypothalamus, where it may be hypothesized that it increases GnRH release.

Magnussen I, Nielsen-Kudsk F. Bioavailability and related pharmacokinetics in man of orally administered L-5-hydroxytryptophan in steady state. Acta Pharmacol Toxicol (Copenh). 1980 Apr;46(4):257-262.
Abstract: The bioavailability of orally administered L-5-hydroxytryptophan in steady state was investigated at four increasing multiple dose levels in five patients suffering from various myoclonic disorders. An L-aromatic amino acid decarboxylase inhibitor was co-administered in all the experiments. The disposition pharmacokinetics of the amino acid had been established in the same patients in preceding intravenous single dose experiments. The finding of a direct proportionality between the size of the oral dose level of L-5-hydroxytryptophan and the corresponding areas under the plasma concentration curves within a dosage interval at steady state strongly indicates dose independent, linear pharmacokinetics of the compound. The systemic availability of L-5-hydroxytryptophan exhibited an interindividual range of 47-84%, with a mean value of 69.2% +/- 4.7 S.E.M. The absorption took place at a rather slow rate as judged from times of 1.8 to 3.3 hours elapsing from administration of the compound until occurance of the maximum measured plasma concentrations. Transitory nausea and vomiting were only recognized in few instances during the gradual building up of increasing steady state levels of L-5-hydroxytryptophan in the patients, and the importance of a slow initiation of therapeutical treatment with the amino acid is emphasized.

Magnussen I, Van Woert MH. Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors. Eur J Clin Pharmacol. 1982;23(1):81-86.
Abstract: L-5-Hydroxytryptophan (5HTP) and its major metabolites 5-hydroxytryptamine (5HT) and 5-hydroxyindoleaceticacid (5HIAA) were measured in blood and cerebrospinal fluid from neurological patients receiving steady state treatment with 5HTP. There was accumulation of 5HT in blood platelets and 5HIAA in plasma in all patients, despite concomitant administration of the L-aromatic amino acid decarboxylase inhibitors, carbidopa and benserazide. There was no correlation between the 5HTP dose and the circulating concentrations of the aminoacid or its metabolites. Preliminary comparison of the biochemical and therapeutic effects of carbidopa versus benserazide suggest that 5HTP: carbidopa is superior to 5HTP: benserazide. A direct proportionality between plasma 5HTP concentrations and the levels of 5HTP in the lumbar cerebrospinal fluid was found. The binding to serum proteins of 5HTP in the clinically relevant concentration range of 10 to 100 microM was investigated; 19% of circulating 5HTP was bound to serum proteins. 5HTP did not displace protein-bound tryptophan in serum.

Magnussen I, Jensen TS, Rand JH, Van Woert MH. Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man. Acta Pharmacol Toxicol (Copenh). 1981 Sep;49(3):184-189.
Abstract: Single oral doses of L-5-hydroxytryptophan (5-HTP) were administered in combination with L-aromatic amino acid decarboxylase inhibitors. The time courses of plasma concentrations of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and the concentrations of 5-HT in blood platelets were measured. Carbidopa enhanced the rise in plasma concentrations of 5-HTP 5-15 fold and counteracted the increase in plasma 5-HIAA levels induced by 5-HTP alone. A single dose of the decarboxylase inhibitor was equipotent to 14 days' pretreatment. Plasma or platelet concentrations of 5-HT failed to reflect the metabolism of 5-HTP. The ratio of 5-HTP to carbidopa influenced the systemic bioavailability of single dose administered 5-HTP indicating dose dependent absorption kinetics. Co-administration of L-dopa with 5-HTP and decarboxylase inhibitors had no effect on gastrointestinal absorption of 5-HTP in six parkinsonian patients.

Magnussen I, Dupont E, Engbaek F, de Fine Olivarius B. Post-hypoxic intention myoclonus treated with 5-hydroxytryptophan and an extracerebral decarboxylase inhibitor. Acta Neurol Scand 1978 Apr;57(4):289-294.
Abstract: Post-hypoxic intention myoclonus successfully treated by long-term administration of the combination of 5-hydroxytryptophan and carbidopa is described. Persistent euphoria and diarrhoea were essential side effects. Methysergide (12 mg/day) blocked the therapeutic effect, indicating a specific serotoninergic function of precursor loading with 5-hydroxytryptophan. Tryptophan (8 g/day) had no effect on the myoclonus suggesting a reduced tryptophan hydroxylase activity. Plasma concentrations of 5-hydroxytryptophan in the range of 10--30 micromoles per liter were obtained during maintenance therapy with 900 mg 5-hydroxytryptophan per day in combination with 150 mg carbidopa per day.

Meltzer H, Bastani B, Jayathilake K, Maes M.  Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder. Neuropsychopharmacology. 1997 Jul;17(1):1-11.
Abstract: It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity. The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol and prolactin (PRL) concentrations were studied in patients with major depression or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD. The L-5-HTP-induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different. The results suggest that fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated stimulation of cortisol and PRL secretion in humans, consistent with available evidence that fluoxetine treatment, but not tricyclic antidepressants, increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism.

Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol 1993;31(4):603-630.
Abstract: This overview summarizes the major and minor side effects and drug interactions of fluoxetine. The adverse reactions include the "serotonin syndrome", cardiovascular complications, extrapyramidal side effects such as akathisia, dyskinesias, and parkinsonian-like syndromes and an apparently increased risk of suicidality. Fluoxetine-induced mania and hypomania, seizures and sexual disorders are evaluated along with minor symptoms of allergic reactions, stuttering, hematological changes, psoriasis, and inappropriate secretion of the antidiuretic hormone. The major fluoxetine-drug interactions involve the amino acids L-dopa and L-tryptophan, anorexiants, anticonvulsants, antidepressants, anxiolytics, calcium channel blockers, cyproheptadine, lithium salts, and drugs of abuse. The underlying mechanism and the paradoxical effects of fluoxetine are addressed.

Michelson D, Page SW, Casey R, Trucksess MW, Love LA, Milstien S, Wilson C, Massaquoi SG, Crofford LJ, Hallett M, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol. 1994 Dec;21(12):2261-2265.
Abstract: OBJECTIVE. To determine whether L-5-hydroxytryptophan (L-5-HTP) associated with eosinophiliamyalgia syndrome (EMS) like illness contains impurities in a fashion similar to that described in L-tryptophan associated with EMS. METHODS. Members of a family who became ill after exposure to L-5-HTP were evaluated at the National Institutes of Health. Data from patients with extended exposure to L-5-HTP were also examined. Samples of L-5-HTP were examined using high performance liquid chromatography. RESULTS. One member of the family had EMS, and 2 others had eosinophilia. No patient in the other group reviewed developed the syndrome, although 2 patients developed eosinophilia. The L-5-HTP used by the family contained an impurity not present in samples from the other patient group. After replacement with L-5-HTP not containing this impurity, eosinophilia in 2 family members resolved. CONCLUSION. Some L-5-HTP contains impurities that may be related to L-5-HTP associated EMS.

Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology. 1991;24(2):53-81.
Abstract: H.M. van Praag has been suggesting a reappraisal of syndromes in psychiatry for over 20 years. He has tried to define syndromes originating from the same biochemical disorder. He has denoted this concept as 'functional psychopathology'. As an example of such a functional syndrome, he has cited the serotonin-shortage syndrome which unifies various psychiatric symptoms under a new point of view. The treatment of the serotonin-shortage syndrome is best served by psychopharmaca which raise the metabolism of serotonin in the synaptic cleft, e.g. the selective serotonin re-uptake inhibitors. Borrowing F. Freyhan's concept of 'target symptoms', one can now speak of 'functional target syndromes', within the frame of functional psychopathology.

Sargent PA, Williamson DJ, Cowen PJ. Brain 5-HT neurotransmission during paroxetine treatment.Br J Psychiatry. 1998 Jan;172:49-52.
Abstract: BACKGROUND: Animal experimental studies suggest that repeated administration of selective serotonin reuptake inhibitors (SSRIs) produces complex adaptive changes in brain serotonin (5-HT) pathways. The effect of these adaptive changes on different aspects of brain 5-HT neurotransmission and their clinical consequences are not well understood. METHOD: We studied the effect of repeated administration of the SSRI, paroxetine (20 mg daily), on the cortisol responses to the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in healthy subjects and depressed patients. RESULTS: In healthy subjects, following one week of paroxetine treatment there was a large increase in the cortisol response to 5-HTP. This increase had all but disappeared following 3 weeks treatment. In contrast, in depressed patients treated with paroxetine for 8 weeks, the cortisol response to 5-HTP was significantly increased. CONCLUSIONS: SSRI treatment in depressed patients produces a persistent increase in the cortisol response to 5-HTP, a probable measure of neurotransmission at central 5-HT2 receptors. Potentiation of 5-HT2 neurotransmission is unlikely to account for the efficacy of SSRIs in major depression but might underlie their actions in obsessive-compulsive disorder and also perhaps certain of their adverse effects, notably sexual dysfunction.

Soulairac A, Lambinet H. [Clinical studies of the effect of the serotonin precursor, L-5-hydroxytryptophan, on sleep disorders]. Schweiz Rundsch Med Prax. 1988 Aug 23;77(34A):19-23. [Article in French]

Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S, Osterland CK. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980 Oct 2;303(14):782-787.
Abstract: A scleroderma-like illness developed in a patient treated with L-5 hydroxytryptophan (L-5HTP) and carbidopa for intention myoclonus. The patient had high plasma kynurenine levels that remained high when the L-5HTP-carbidopa combination was discontinued, However, levels rose futher on drug rechallenge, suggesting that the drug unmasked an abnormality in one of the enzymes that catabolize kynurenine. Plasma kynurenine was also determined to be high in seven of 15 patients wth idiopathic scleroderma, but not in eight patients with intention myoclonus treated with L-5HTP and a decarboxylase inhibitor and in whom scleroderma did not develop or in 10 patients with Parkinson's disease treated wth L-dopa and carbidopa. Our data and studies in the literature suggest that two factors may be important in the pathogenesis of some scleroderma-like illness: high plasma serotonin and the abnormality associated with elevated kynurenine.

Threlkeld DS, ed. Central Nervous System Drugs, Antidepressants, Selective Serotonin Reuptake Inhibitors. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparison, Apr 1997.

Van Woert MH, Rosenbaum D, Howieson J, Bowers MB Jr. Long-term therapy of myoclonus and other neurologic disorders with L-5-hydroxytryptophan and carbidopa. N Engl J Med. 1977 Jan 13;296(2):70-75.
Abstract: We evaluated the therapeutic effect of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin (5-hydroxytryptamine), combined with carbidopa, a peripheral decarboxylase inhibitor, in patients with intention myoclonus and examined the serotonin metabolites in spinal fluid, blood and urine before and during therapy. In 18 patients with intention myoclonus due to anoxia or other brain damage, 11 derived more than 50% overall improvement during treatment with L-5HTP and carbidopa. Spinal-fluid 5-hydroxyindoleacetic acid was 35% lower in patients with intention myoclonus than in controls (P less than 0.05). Therapy with L-5HTP and carbidopa increased the concentration of serotonin metabolites in urine and spinal fluid. We postulate that a deficiency of brain serotonin is causally related to intention myoclonus and that the therapeutic effect of L-5HTP and carbidopa may be due to the repletion of serotonin in regions of the brain where serotoninergic neurons have degenerated.

Van Woert MH. Myoclonus and L-5-hydroxytryptophan (L-5HTP). Prog Clin Biol Res. 1983;127:43-52.

Williamson BL, Tomlinson AJ, Glleich GJ, et al. Problems with over-the-counter 5-hydroxytryptophan. Nature Med 1998;4:983.