title: Clinical relevance of serum nortriptyline and 10-hydroxy-nortriptyline measurements in the depressed elderly: a multicenter pharmacokinetic and pharmacodynamic study.
abstract: In a recent placebo-controlled multicenter study, 38 patients, ranging in age between 62 and 88 years (median, 71) were treated with nortriptyline (NT) for up to 7 weeks. NT was administered in a divided dose of 75 mg daily and serum NT (se NT), and its 10-hydroxy-metabolites (se OH-NT) were determined at various intervals. Several clinical measures of efficacy, including the 17-item Hamilton Rating Scale for Depression, were evaluated weekly as well as side effects (anticholinergic) and electrocardiogram (ECG) changes. Eighty-one percent of patients had NT levels in the previously defined therapeutic range of 50 to 170 ng/ml, with steady state reached between 1 and 3 weeks. There was little individual variation in drug kinetics and metabolism over the study period. In general se OH-NT levels were not greater than those of se NT. Pharmacodynamic analyses showed that patients with moderate to severe anticholinergic side effects [CSE(+)] had significantly higher NT levels than those with mild or no symptoms [CSE(-)]. Furthermore, repeated-measures ANOVA modeled over time showed a highly significant decrease in clinical measures in both CSE groups of patients and also a highly significant group-time interaction. Higher se OH-NT levels were associated with less anticholinergic side effects. No ECG changes were observed.
authors.affiliation: Douglas Hospital Research Centre, McGill Uruversity, Montréal, Québec, Canada.
authors.forename: N M
authors.initials: NM
authors.lastname: Kin
authors.forename: N
authors.initials: N
authors.lastname: Klitgaard
authors.forename: N P
authors.initials: NP
authors.lastname: Nair
authors.forename: M
authors.initials: M
authors.lastname: Amin
authors.forename: P
authors.initials: P
authors.lastname: Kragh-Sorensen
authors.forename: G
authors.initials: G
authors.lastname: Schwariz
authors.forename: S K
authors.initials: SK
authors.lastname: Ahmed
authors.forename: P
authors.initials: P
authors.lastname: Holm
authors.forename: C
authors.initials: C
authors.lastname: Katona
authors.forename: K
authors.initials: K
authors.lastname: Stage
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003866:Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000009:adverse effects / Q000097:blood* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009661:Nortriptyline