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PubMed1986

Preliminary data on the relationship between nortriptyline plasma level and response in depressed children.

Twenty-two subjects 6-12 years old who met Research Diagnostic Criteria and DSM-III criteria for major depressive disorder received a fixed daily dose of nortriptyline during an 8-week protocol. Weekly plasma levels were measured; the raters performing behavioral assessments were blind to these levels. There was a highly significant difference between the mean steady-state plasma levels and the milligram-per-kilogram doses of the responders and nonresponders. The data suggest that the lower limit of the therapeutic range of nortriptyline in children (over 60 ng/ml) is similar to that reported for adults. The disadvantages of the use of a milligram-per-kilogram dose rather than a pharmacokinetic approach are discussed.

Age Factors↗

PubMed1991

Serum nortriptyline levels in nursing mothers and their infants.

The nortriptyline levels of seven depressed mothers and their breast-fed infants were obtained. Nortriptyline was not detected in the infants' sera. However, two of four infants evaluated developed low concentrations of 10-hydroxynortriptyline. No adverse effects were observed.

Breast Feeding↗

PubMed1989

Treatment of depressed tinnitus patients with nortriptyline.

Patients disabled by tinnitus show a high prevalence of major depression. Furthermore, tinnitus produces patterns of disability similar to those produced by major depression. To explore further this link between tinnitus and depression, and to investigate the efficacy of treating depression in the treatment of tinnitus, a single-blind, placebo-washout, nonrandomized pilot study of the tricyclic antidepressant nortriptyline (hydrochloride) was undertaken in disabled tinnitus patients who also met diagnostic criteria for major depression. Nineteen patients began the study, two responded to placebo, and two dropped out prior to completion. Fourteen considered their tinnitus improved, and 12 chose to continue taking nortriptyline after the study. Depression severity decreased, on the average, by 65% (p less than .0001). Tinnitus loudness measured by audiometric matching decreased by a mean of 10 dB or 50% (p less than .02). Self-reports of tinnitus loudness and severity, somatic and psychologic symptoms, and psychosocial dysfunction all showed significant improvement with treatment. These results suggest that what initially appears to be an irreversible otologic disability in these patients may be in large part a reversible psychiatric disability.

Adolescent↗

PubMed1978

Radioimmunoassay of amitriptyline and nortriptyline in body fluids.

A radioimmunoassay for the measurement of amitriptyline and nortriptyline in serum, saliva, and urine is described. The sensitivity of the assay is such that 0.5 ng/ml of drug can be measured, although the assay does not distinguish between amitriptyline and nortriptyline. Other tricyclic compounds cross-react with the antiserum to varying degrees, but the metabolites of amitriptyline did not significantly cross-react. Total tricyclic compounds were detected in serum and saliva after single oral doses of amitriptyline, although the absorption was slow.

Amitriptyline↗

PubMed1986

Exacerbation of acute intermittent porphyria by nortriptyline.

Many medications have been reported to produce attacks of acute intermittent porphyria (AIP). Nortriptyline has been reported to be safe in porphyric patients. We present a case of AIP exacerbated by nortriptyline.

Acute Disease↗

PubMed1982

The clinical efficacy and side-effects of mianserin and nortriptyline in depressed out-patients: a double-blind randomized trial.

A double-blind randomized study was performed in 86 depressed out-patients, in order to compare the efficacy and tolerance of mianserin (30 to 60 mg daily) with that of nortriptyline (75 to 150 mg daily). Both drugs were administered for 6 weeks after a wash-out period of 1 week. The Hamilton Rating Scale for Depression was used weekly and the Clinical Global Impression Scale at the end of treatment. Both preparations proved to be effective, with no significant differences in response. However, tolerance in the mianserin group was much better than in the nortriptyline group. Significant differences were found mainly in the incidence and severity of tachycardia, dry mouth, constipation, sweating, insomnia, agitation and oedema.

Adult↗

PubMed2000

Release of nortriptyline hydrochloride from oil-water microemulsions.

The release of nortritptyline hydrochloride from oil-in-water (o/w) microemulsions (isopropyl myristate as oil, propylene glycol as cosurfactant, polysorbate 80 as surfactant and phosphate buffer, pH 7.4, as the continuous phase) containing increasing concentrations of polyethylene glycol 400, used to facilitate the diffusion of a drug from the inner oily phase of the microemulsion to the outer aqueous phase of such a dispersion system, was studied by determining the permeability constants of the drug through hydrophilic and lipophilic membranes separating the o/w microemulsions from the receiving aqueous phase (phosphate buffer pH 7.4). The permeability of nortriptyline hydrochloride from microemulsions through the lipophilic membrane increased as the concentration of polyethylene glycol 400 in the disperse system increased. The apparent permeability constant for nortriptyline hydrochloride, from the microemulsion without polyethylene glycol, was 1.36 x 10(-3) cm x h(-1), it increased up to 7.80 x 10(-3) cm x h(-1) in the presence of polyethylene glycol at a concentration of 50% (v/v) of the initial volume of the aqueous phase.

Adrenergic Uptake Inhibitors↗

PubMedDate not supplied

Prediction of steady-state nortriptyline plasma levels by the repeated one-point method.

10 psychiatric inpatients with a diagnosis of depression were entered into a prospective study to investigate the repeated one-point method as a method of predicting steady-state concentrations for nortriptyline. Four males and 4 females completed all requirements of the protocol. Single plasma concentrations obtained after the first and second daily doses were found to be accurate predictors of the steady-state minimum plasma concentrations. The difference between the measured and the predicted steady-state minimum values ranged from 2.10 to 32.7 micrograms/L with a standard deviation 10.4 and a mean of 10.5 micrograms/L, assuming a normal distribution. The correlation coefficient of predicted versus measured concentrations was 0.946 with 90% confidence limits, ranging from 0.800 to 0.990. The repeated one-point method was found to be an accurate predictor of steady-state minimum plasma concentrations in patients receiving nortriptyline. This method should allow for individual adjustment of dose while minimising the time required to achieve therapeutic, non-toxic plasma concentrations.

Adult↗

PubMed1997

Does lorazepam impair the antidepressant response to nortriptyline and psychotherapy?

BACKGROUND: This analysis sought to determine whether lorazepam influences time to response or rate of response in elderly depressed patients receiving nortriptyline and psychotherapy and to examine clinical and polysomnographic correlates of lorazepam treatment. METHOD: Patients with recurrent major depressive disorder (N = 119; mean +/- SD age = 68.0 +/- 6.1 years; diagnosis defined by Research Diagnostic Criteria) received acute treatment with nortriptyline and interpersonal psychotherapy. Thirty-five patients received open-label adjunctive lorazepam for anxiety or insomnia symptoms (LZ+) and 84 did not. Statistical analyses were conducted between the LZ+ group and a group of 35 patients who received no lorazepam (LZ-) and were matched for anxiety level. Patients had polysomnographic studies prior to treatment and after remission of depressive symptoms. RESULTS: The LZ+ group reported more anxiety on the Brief Symptom Inventory (p = .04) compared with the remaining 84 patients. The LZ+ group had a greater proportion of endogenous depression subtype than the anxiety-matched LZ- group, in addition to more abnormal EEG sleep (higher percentage of REM sleep, shorter REM latency, lower delta sleep ratio). Mean time to initial antidepressant response was no different between groups. However, a significantly greater proportion of LZ+ than LZ- patients responded to acute treatment (91.4% vs. 71.4%; p < .03). CONCLUSION: Adjunctive lorazepam does not slow the antidepressant response to combined antidepressant/psychotherapy treatment in elderly depressed patients, and it is associated with a greater likelihood of antidepressant response. A greater percentage of patients treated with lorazepam have endogenous depression subtype and abnormal sleep findings (EEG) than those who are not treated with lorazepam. Adjunctive lorazepam is useful for treating anxiety in elderly depressed patients.

Age Factors↗

PubMed1999

Brain morphology and response to nortriptyline in geriatric depression.

In geriatric patients with major depression (N=15), the authors compared response to treatment with nortriptyline as it relates to brain morphology assessed by computed tomography. There was a significant negative association between ventricle-brain ratio and response to nortriptyline (rs=-0.63; P=0.015).

Aged↗

PubMed2000

Effects of nortriptyline and paroxetine on QT variability in patients with panic disorder.

This study investigated beat-to-beat QT variability in patients with panic disorder before and after treatment with nortriptyline (n = 13) and paroxetine (n = 16), using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden cardiac death. QTvi (QT variability index: a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) was significantly higher in supine posture in patients with panic disorder treated with nortriptyline (P = 0.006) but not paroxetine. Thus paroxetine may be a better drug of choice especially in patients with coexisting cardiac disease. These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression. QTvi can be a valuable noninvasive measure of temporal repolarization lability, especially to study the side effects of medications which affect cardiac autonomic function.

Adult↗

PubMed2000

Weight change in older depressed patients during acute pharmacotherapy with paroxetine and nortriptyline: a double-blind randomized trial.

The authors examined weight change in 32 elderly patients treated for 12 weeks with either nortriptyline or paroxetine during acute-phase pharmacotherapy. Random assignment to treatment and double-blind assessment of weight change were performed, including ascertainment of premorbid (i.e., pre-depression) weight. Pretreatment severity of depression was correlated with weight loss during the depressive episode and depression-related weight loss, in turn, correlated with weight regained during antidepressant treatment. There was no differential weight change associated with nortriptyline vs. paroxetine. Rather, subjects in both groups approximated their premorbid weights by 12 weeks of acute-phase pharmacotherapy with either agent. However, additional investigation of weight change during continuation and maintenance pharmacotherapy is necessary and would be clinically useful for the long-term management of elderly patients with depression.

Aged↗

PubMedDate not supplied

A double-blind, randomized, controlled study of amitriptyline, nortriptyline and placebo in patients with fibromyalgia. An analysis of outcome measures.

OBJECTIVE: To study the efficacy and tolerability of amitriptyline and nortriptyline in a Brazilian population with fibromyalgia and to evaluate the instruments used to measure the efficacy of the treatment. METHODS: A total of 118 fibromyalgia patients were randomly assigned to 3 groups: amitriptyline (AM, n = 40), nortriptyline (NOR, n =38) and placebo (PL, n = 40), and were blindly given 25 mg at bedtime of the assigned treatment for 8 weeks. Clinical evaluation before and at the end of the study included the number of tender points (NTP), FIQ score (FIQ), and global improvement as reported by the patients on a verbal scale (VSGI). RESULTS: The 3 groups were comparable at baseline for all the parameters studied. After 8 weeks, the 3 groups improved in all parameters: (36.5% AM, 26.7% NOR and 24% PL patients improved on FIQ; 13.9% AM, 19.5% NOR and 8.57% PL patients improved on NTP; 86.5% AM, 72.2% NOR and 57.6% PL patients improved on VSGI). Only the AM group differed from the PL group on VSGI. Side effects were noted among the groups, but none were serious (16 in the AM group, 31 in the NOR group, and 25 in the PL group). CONCLUSION: All three groups improved after treatment. Only the patient's subjective global assessment of improvement differed between the AM patients and the PL group (p < or = 0.03). In fibromyalgia, placebo groups are important in drug trials. Different measures of therapeutic effect are not better than the patient's self assessment.

Adolescent↗

PubMed1988

Nortriptyline in the treatment of panic disorder and agoraphobia with panic attacks.

Thirty-four consecutive patients with panic disorder or agoraphobia with panic attacks were treated with nortriptyline at the LAC-USC Medical Center's Anxiety Disorders Clinic. Fourteen (67%) of the 21 completers totally lost their panic attacks, five (24%) showed partial improvement, and two (10%) showed no improvement. The relationship of treatment outcome to pretreatment and posttreatment measures of depression is discussed, in addition to the potential role of nortriptyline in treating panic attacks in clinical practice.

Adult↗

PubMed1987

Prospective study of scheduled withdrawal from nortriptyline in children and adolescents.

Thirty 6- to 16-year-old subjects were gradually tapered from their maintenance dose of nortriptyline while being monitored for withdrawal effects. Five subjects had brief gastrointestinal distress that did not require the administration of an extra dose. The results of this open study suggest that scheduled tapering of nortriptyline will preclude withdrawal symptoms in most pediatric patients.

Adolescent↗

PubMed1987

Child and adolescent nortriptyline single dose pharmacokinetic parameters: final report.

This is the final report of a study of single dose pharmacokinetic parameters of nortriptyline in children and adolescents 5 to 16 years old (N = 64). The data were analyzed separately for the 5- to 12-year-olds (N = 41) and for the 13- to 16-year-olds (N = 32). The results confirm the preliminary findings of the similarity of the pharmacology of nortriptyline between the pediatric and adult age groups with respect to a logarithmically linear rate of elimination and a wide interindividual rate of metabolism. The 5- to 12-year-olds had a significantly shorter mean half-life and a significantly greater mean apparent oral clearance than the 13- to 16-year-olds. The mean half-life in the 5- to 12-year-olds was 20.8 +/- 7.2 (range, 11.2 to 42.5) hours and in the 13- to 16-year-olds was 31.1 +/- 19.8 (range, 14.2 to 89.4) hours. A twice a day dosage regimen is recommended for the entire 5- to 16-year-old group based on their range of half-lives.

Adolescent↗

PubMedDate not supplied

[Double blind clinical study of mianserin and nortriptyline (author's transl)].

The present study was done in double blind during 6 weeks on 36 depressed patients having a minimal score of 15 on the Hamilton rating scale. Seventeen received mianserin and nineteen nortriptyline. A comparable therapeutic efficacy was observed for both drugs, without significant differences for the delay of action or the activity during 6 weeks. The number of side-effects was much more elevated for nortriptyline, and a significant difference was particularly observed for the frequency and severity of tachycardia, dry mouth and oedema.

Adolescent↗

PubMed1985

Nortriptyline-induced severe hyperventilation.

A 61-year-old man with end-stage renal disease developed severe hyperventilation following nortriptyline hydrochloride usage for depression. He required mechanical ventilation and paralysis to correct severe respiratory alkalosis. To our knowledge, nortriptyline usage has not been previously associated with hyperventilation.

Alkalosis, Respiratory↗