Nortriptyline plasma levels and therapeutic response

Abstract

Eighteen depressed outpatients were treated for 6 wk with a mean daily dose of 121 mg of nortriptyline. The mean plasma level was 138 ng/ml during treatment. Therapeutic response was monitored by the Zung Self-Rating Depression Scale and the Hamilton Depression Scale administrered by two psychiatrists blind to the tricyclic used, dose, and plasma levels. Eight patients recovered (Hamilton less than or equal to 6) by the fourth week and 12 by the sixth week. During the steady-state (wk 4 to 6) there was a positive correlation between the weekly Hamilton scores and the weekly nortriptyline levels (p less than 0.01). The 9 patients with mean plasma levels between 50 and 139 ng/ml had a better therapeutic response after 6 wk measured by percent recovered (p less than 0.005). Zung score (p less than 0.05), and Hamilton score (p less than 0.025) than the 9 patients with mean plasma levels between 140 and 260 ng/ml.

Symptoms of Major Depression and Tricyclic Side Effects in Primary Care Patients

“…It extends our understanding of the course of these somatic symptoms beyond the time frame previously reported for depressed psychiatric, 13,15 geriatric, 16 or primary care patients. 18 Our findings clearly support the concept that treatment of the underlying depressive episode can reduce the number and severity of depression-associated somatic symptoms experienced by primary care patients.…”

“…This finding resembles other reports of patients recovering from depression using tricyclic antidepressants. 13,16,18 Furthermore, we found that the severity of these dry mouth symptoms declined during continuation therapy to approach that found before commencing pharmacotherapy.…”

“…Presumably physicians prescribe antidepressants at quite low initial and continuing dosages so that discomforts are better tolerated and participation in treatment is sustained. 12 Still, the physician must consider whether the discomforting psychological and somatic symptoms attributed to the antidepressant medication are actually manifestations of the mood disorder itself.Symptoms resembling the side effects of tricyclic antidepressants have been found among depressed psychiatric, 13-15 geriatric, 16 and primary care [17][18][19] patients even before these medications were provided them. Given these earlier reports, more information is needed about the relation between subjective symptoms resembling tricyclic side effects and the severity of the depressive episode along with the influence of a comorbid anxiety disorder on these symptoms.…”

“…Symptoms resembling the side effects of tricyclic antidepressants have been found among depressed psychiatric, [13][14][15] geriatric, 16 and primary care [17][18][19] patients even before these medications were provided them. Given these earlier reports, more information is needed about the relation between subjective symptoms resembling tricyclic side effects and the severity of the depressive episode along with the influence of a comorbid anxiety disorder on these symptoms.…”

Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6‐an evaluation with the nonparametric maximum likelihood method.

“…It was the first antidepressant for which a bell-shaped concentration-effect relationship was postulated [1]. Subsequent studies have confirmed that the therapeutic effect in most patients decreases at concentrations above circa 600 nM [2][3][4]. A proposed lower effect limit at 200 nM is based on only one pilot study [1].…”