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Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline

par Mendlewicz, Julien ;Pinder, Margaret;Stulemeijer, S.M.;Van Dorth, R.
Référence Journal of affective disorders, 4, 3, page (219-226)
Publication Publié, 1982

Article révisé par les pairs

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Résumé :

A group of 20 inpatients with moderate to severe primary to severe primary affective disorder received 14 days of placebo treatment and were then randomly allocated to receive mianserin 10 mg 3 times daily or identical amitriptyline 25 mg 3 times daily for 1 week followed by 60 mg mianserin or 150 mg amitriptyline daily for a second week. Patients were rated for side-effects and depression (Hamilton Depression Scale) on days 0, 7, 14, 21 and 28. Probenecid 100 mg/kg was administered in 3 divided doses on days 13/14 and on days 27/28 of the trial, followed by collection of CSF. Blood samples for determination of antidepressant levels were collected on day 27. Both mianserin and amitriptyline produced a significant decrease in CSF levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but only amitriptyline significantly lowered CSF levels of 5-hydroxyindole-3-acetic acid (5-HIAA). Neither drug affected CSF levels of homovanillic acid (HVA). Both mianserin and amitriptyline produced significant but indistinguishable improvement in mean Hamilton scores over 2 weeks of treatment. There was no relationship between therapeutic response and either plasma antidepressant levels or pre-treatment CSF monoamine metabolite levels in this small group of patients. The reductions of CSF levels of metabolites of NA (MHPG) and 5-HT 95-HIAA) are consistent with the known effects of amitriptyline on amine uptake. Mianserin may reduce CSF MHPG levels as a result of its effects upon NA release and/or uptake, but it appears to be devoid of influence upon central 5-HT metabolism.