Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline.
A group of 20 inpatients with moderate 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 his small group of patients. The reductions of CSF levels of metabolites of NA (MHPG) and 5-HT (5-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.
D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000523:psychology; D003984:Dibenzazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006018:Glycols / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008803:Mianserin / Q000627:therapeutic use*; D008875:Middle Aged; D010648:Phenylacetates / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales
D003984:Dibenzazepines; D006018:Glycols; D010648:Phenylacetates; D000639:Amitriptyline; D008803:Mianserin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid