5-hydroxytryptophan (5-HTP) - toxicitet/biverkningar. Se brev

Fråga: 5-hydroxytryptophan (5-HTP) - toxicitet/biverkningar. Se brev

Sammanfattning: The principal side-effects of 5-HTP are gastrointestinal. In order to prevent them it has been suggested to associate a peripheral decarboxylase inhibitor or to use coated tablets. Animal toxicology has not yet been systematically studied.

Svar: 5-HTP, a precursor of serotonin, is used in the treatment of depression according to the serotonin hypothesis of effective disorders. It is also used for treatment of different kinds of involuntary movement disorders. In fact in the CSF of patients with intention myoclonus the major catabolite of serotonin has been found to be low (1). The drug is not registered in Sweden although it is registered in other countries e.g. Germany, France and Italy.

The principal side effects are gastrointestinal such as nausea, anorexia, vomiting and diarrhea. They are dose-dependent and can be largely avoided by giving 5-HTP in combination with a peripheral decarboxylase inhibition or by using tablets with enteric coating. Such a preparation is not yet commercially available (2).

The frequency of gastrointestinal side-effects has been studied by Nakajima et al (1978; 3). Disturbances were found in 13 of 59 patients treated with a daily dose of 150-300 mg of 5-HTP, although all patients were protected by simultaneous administration of metoclopramide. Other side-effects occasionally observed included sweating, tremor, dizziness, disturbances of urination, flushes and headache. In animal studies (rat) nephrotoxicity has been shown at high doses (300 mg/kg).

Magnussen and Nielsen-Kudsk (1980; 4) investigated the steady-state pharmacokinetics and bioavailabililty of 5-HTP administered orally at increasing dose together with carbidopa and the relationship between the dose level and the frequency of gastrointestinal side effects. Transitory nausea and vomiting were found in few instances during the gradual building up of increasing steady-state levels of 5-HTP in patients. They emphasize the importance of a slow initiation of treatment in order to induce tolerance against the unwanted effects of the drug. Systemic availability of 5-HTP exhibited a range of 47-84 per cent.

Van Hiele (1980; 5) reports an "astonishing recovery" without side-effects in some 50 % of 99 "therapy resistant" depressive patients treated with 5-HTP. This is a finding that indeed has to be validated.

In the literature is described a patient with intention myoclonus who developed scleroderma-like illness during treatment with 5-HTP and carbidopa. The 5-HTP dosage (1400 mg per day over a period of 20 months) was higher than that used in depression (50-500 mg daily) (6). It has been reported (7) that l-tryptophan can induce in rats bladder, uterus and lung tumours. In our literature we have found nothing on this.