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Clinical and biochemical effects during treatment of depression with nortriptyline: The role of 10‐hydroxynortriptyline
Author(s) -
Nordin Conny,
Bertilsson Leif,
Siwers Bo
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.101
Subject(s) - nortriptyline , metabolite , medicine , chemistry , endocrinology , cerebrospinal fluid , plasma concentration , amitriptyline
Plasma concentrations of nortriptyline (NT) and its major metabolite 10‐hydroxy‐NT (10‐OH‐NT) were measured in 30 patients with depression, treated with NT for 3 weeks. Nine patients who recovered completely had plasma concentrations of NT and 10‐OH‐NT ranging from 358 to 728 nmol/L and from 428 to 688 nmol/L, respectively. Of the 21 patients who did not recover completely, only four had plasma concentrations within the window limited by these two plasma concentration ranges. A correlation was found between the degree of amelioration and the plasma concentration of NT (r s = 0.469; P < 0.01). Lumbar punctures were performed in 26 patients before and after 3 weeks of NT treatment. During treatment there was a 30.9% mean decrease in the noradrenaline metabolite 4‐hydroxy‐3‐methoxyphenylglycol (HMPG) in cerebrospinal fluid (CSF). We could not evaluate the extent to which this decrease was caused by NT or 10‐OH‐NT, respectively, because both are strong inhibitors of noradrenaline uptake. The ratio between the concentration of NT and 10‐OH‐NT in CSF correlated to the reduction of HMPG in CSF (r = 0.397; P < 0.05) and to the amelioration of depression (r s = 0.623; P < 0.001). This might indicate that NT and 10‐OH‐NT interact on the noradrenaline system in a nonadditive way. During treatment there was a 15.2% decrease in CSF concentration of the serotonin metabolite 5‐hydroxyindoleacetic acid. The reduction was significantly correlated to the CSF concentration of NT but not to that of 10‐OH‐NT. This is in accordance with the fact that NT is a more potent inhibitor of serotonin uptake than is 10‐OH‐NT. The dopamine metabolite homovanillic acid in CSF decreased significantly by 10.0%. The biochemical data indicate that noradrenergic, serotoninergic, and dopaminergic systems are affected by NT treatment and that 10‐OH‐NT might be more selective on noradrenergic neurons than the parent drug. Clinical Pharmacology and Therapeutics (1987) 42, 10–19; doi: 10.1038/clpt.1987.101