Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nortriptyline”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

Relationships among nortriptyline, 10-OH(E)nortriptyline, and 10-OH(Z)nortriptyline steady-state plasma levels and nortriptyline dosage.

The postulated therapeutic activity of nortriptyline metabolites has prompted investigation of dosage adjustments based on plasma levels of nortriptyline (NT) and its metabolites. The method assumes that metabolite concentrations vary independently of nortriptyline concentrations among patients. This study tests that assumption and investigates different means of obtaining metabolite concentrations. Forty-two psychiatric inpatients were divided into three maintenance dose groups: 50, 100, and 150 mg NT/day. After a 28-day study for each inpatient, steady-state plasma concentrations for days 14, 18, 21, 25, and 28 were determined. Concentrations were averaged for each patient. Nortriptyline concentrations did not correlate well with corresponding 10-OH(E)nortriptyline (p greater than 0.05) or 10-OH(Z)nortriptyline concentrations (r2 = 0.31, p less than 0.05). Concentrations of 10-OH(E)nortriptyline did not correlate well with corresponding 10-OH(Z)nortriptyline concentrations (r2 = 0.236, p less than 0.05). Neither dose/body weight nor obesity were good predictors of individual concentrations of nortriptyline, 10-OH(E)nortriptyline, or 10-OH(Z)nortriptyline or even the sum of the three. In conclusion, optimal drug therapy may involve dosage adjustments according to the combined plasma levels of nortriptyline and metabolites. Assurance of obtaining certain plasma concentrations requires plasma level monitoring.

Body Weight↗
PubMed1989

Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients: significance of concurrent medication and the sparteine oxidation phenotype.

Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50% of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steady-state levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (rs = 0.68, n = 55, p less than 0.001) and the nortriptyline/Z-10-OH-nortriptyline ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs = 0.62, p less than 0.01) and E-10-OH-nortriptyline (rs = -0.52, p less than 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs = 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.

Adult↗
PubMed1985

Dose and plasma levels of nortriptyline and chlorpromazine in delusionally depressed adolescents and of nortriptyline in nondelusionally depressed adolescents.

Eight adolescents with major depressive disorder were treated with nortriptyline and six adolescents with delusional depression were treated with combined nortriptyline and chlorpromazine. Dose and plasma levels of nortriptyline for the two groups were compared. The delusional group receiving combined drug treatment needed significantly less nortriptyline than did the nondelusional group receiving only nortriptyline to obtain similar mean steady state plasma levels of the drug. The mean plasma chlorpromazine levels were quite low.

Adolescent↗
PubMed1994

Nonlinear kinetics of nortriptyline in relation to nortriptyline clearance as observed during therapeutic drug monitoring.

From routine therapeutic drug monitoring data, samples from 105 patients with two analyses of nortriptyline at different daily doses were collected. The ratio between concentration and daily dose, which is the reciprocal of the apparent clearance, was compared intra-individually to study the occurrence of dose-dependent kinetics. Subjects with a low or intermediate ratio at the low dose had a higher mean ratio at the high dose, indicating a nonlinear relationship between dose and concentration. The magnitude of the difference was inversely correlated to the ratio at the low dose. No major difference was seen in the ca. 10% of the patients that exhibited the highest ratio at the low dose. This fraction corresponds to the frequency of poor metabolizers of debrisoquine in the population. The metabolism of nortriptyline has been shown to be partly dependent on the debrisoquine hydroxylase CYP2D6. We conclude that dose-dependent kinetics of nortriptyline occurs in subjects with a high or intermediate capacity to eliminate the drug, in accord with debrisoquine hydroxylase being a high-affinity, low-capacity pathway in the elimination of nortriptyline.

Chromatography, High Pressure Liquid↗
PubMed1996

Clinical relevance of serum nortriptyline and 10-hydroxy-nortriptyline measurements in the depressed elderly: a multicenter pharmacokinetic and pharmacodynamic study.

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.

Aged↗
PubMed1991

Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline.

The enantioselectivity of hydroxylation of nortriptyline (NT) to E-10-hydroxynortriptyline (E-10-OH-NT) was studied in human liver microsomes, intestinal homogenate, and patients treated with NT. The rate of formation of (-)-E-10-OH-NT was higher than that of (+)-E-10-OH-NT both in the liver microsomes and in the intestinal homogenate. Quinidine, a prototype competitive inhibitor of the cytochrome P450IID6 ("debrisoquin hydroxylase"), inhibited the formation of (-)-E-10-OH-NT in a concentration-dependent manner in liver microsomes, while the formation of (+)-E-10-OH-NT was hardly affected. This indicates that P450IID6 catalyzes the hydroxylation of NT in a highly enantioselective manner to (-)-E-10-OH-NT in the liver. Another P450 isozyme besides IID6 seems to be responsible for the formation of the (+)-enantiomer in the liver. In intestinal homogenate, the formation of both enantiomers of E-10-OH-NT was inhibited to about the same extent by quinidine, the maximum inhibition being much less than in the liver. In the urine of six patients treated with NT, the (-)-enantiomer accounted for 91 +/- 2% of the unconjugated E-10-OH-NT, and for 78 +/- 6% of the glucuronide conjugates. The study shows that NT is hydroxylated in a highly enantioselective way, probably catalyzed by the polymorphic P450IID6, to (-)-E-10-OH-NT both in vitro in human liver as well as in vivo in patients treated with the drug.

Glucuronates↗
PubMed1979

Displacement of nortriptyline and uptake of 14C-lidocaine in the lung after administration of 14C-lidocaine to nortriptyline intoxicated pigs.

Six anaesthetized Swedish land-race pigs were intoxicated by an intravenous infusion of nortriptyline-HCl (NT) up to a concentration of 4.58 +/- 0.58 (mean +/- S.E.M.) microM in arterial whole blood. A rapid injection of 2 mg/kg b.wt. lidocaine-HCl in the right atrium was followed by a rise in arterial whole blood concentration of NT up to a maximum of 7.32 +/- 0.28 microM NT. Amount displaced NT from the cardio-pulmonary circulation after the 14C-lidocaine bolus, was calculated to be 0.66 +/- 0.03 mumol. Lung uptake of 14C-lidocaine during first-pass through the lung was not influenced to any statistically signficant degree compared to a control group. Thus, first pass uptake (FPU) was 30 +/- 8 (mean +/- S.E.M.)% and 39 +/- 5% respectively. The duration of the QRS-complex of the ECG was increased (P less than 0.01) during the infusion of NT from 0.07 +/- 0.01 (mean +/- S.E.M.) sec. to 0.14 +/- 0.02 sec. when 250 mg NT-HCl had been administered. The QRS-duration was decreased (P less than 0.01) after the injection of the 14C-lidocaine bolus to 0.09 +/- 0.01 sec. Mean arterial blood pressure and heartrate decreased slightly during the infusion of NT, but did not change immediately after the 14C-lidocaine bolus.

Animals↗
PubMed1998

10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes.

OBJECTIVE: To investigate the disposition and effects of nortriptyline and its major metabolite 10-hydroxy-nortriptyline line in panels of white subjects with different CYP2D6 genotypes, including those with duplicated and multiduplicated CYP2D6*2 genes and to evaluate the contribution of the number of functional C gamma P2D6 alleles to the metabolism of nortriptyline, used here as a model drug for CYP2D6 substrates. METHODS: Oral single doses of 25 to 50 mg nortriptyline were given to five poor metabolizers of debrisoquin (INN; debrisoquine) with no functional CYP2D6 gene, five extensive metabolizers with one functional CY2D6 gene, five extensive metabolizers with two functional CYP2D6 genes, five ultrarapid metabolizers with duplicated CYP2D6*2 genes, and one ultrarapid metabolizer with 13 copies of the CYP2D6*2 gene. Plasma kinetics of nortriptyline and 10-hydroxynortriptyline were analyzed. Anticholinergic effects (inhibition of salivation and accommodation disturbances), sedation, blood pressure, and effect on supine and erect pulse rate were measured. RESULTS: There was a clear relation between the C gamma P2D6 genotype and the plasma kinetics of nortriptyline and 10-hydroxynortriptyline. The proportion between the apparent oral clearances of nortriptyline in the groups with 0, 1, 2, 3, and 13 functional genes was 1:1:4:5:17. The proportions between AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratios in the groups with 0, 1, 2, 3, and 13 functional genes were 36:25:10:4:1. Oral plasma clearance of nortriptyline and AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratio both correlated significantly with the debrisoquin metabolic ratio (rS = -0.89, p = 0.0001; rS = 0.92, p = 0.0001). Although ultrarapid metabolizer subjects were given double the nortriptyline dose (50 mg), inhibition of salivation was not more pronounced compared with the other genotype groups given 25 mg nortriptyline. CONCLUSION: The results of this study show the quantitative importance of the CYP2D6 genotype, especially the presence of multiple functional CYP2D6 genes for the pharmacokinetics of nortriptyline and 10-hydroxynortriptyline. Genotyping of subjects with multiple copies of functional genes may be of great value for differentiating ultrarapid metabolizers from patients who do not comply with the prescription and for assuring adequate drug choice and dosage for these patients.

Analysis of Variance↗
PubMed1997

The effects of perphenazine on the concentration of nortriptyline and its hydroxymetabolites in older patients.

Twenty-five older patients who presented with psychotic depression were treated with a combination of nortriptyline and perphenazine. Plasma levels of nortriptyline, E-, and Z-10-OH nortriptyline (E- and Z-10-OH-NT) were measured before and after addition of perphenazine. The mean (+/-SD) initial nortriptyline dose was 59 +/- 24 mg/day, whereas the mean final nortriptyline and perphenazine doses were 56 +/- 24 and 19 +/- 13 mg/day, respectively. The mean plasma level to dose quotient for perphenazine (0.45 +/- 0.34 nM/mg/day) was comparable to the mean quotient reported previously in older psychotic patients treated with perphenazine alone. After addition of perphenazine, the median quotient of nortriptyline plasma level to nortriptyline dose (L/D) increased significantly (from 6.1 to 8.6). This change was inversely correlated with baseline nortriptyline L/D. The median ratio of E-10-OH-NT to nortriptyline plasma level decreased significantly (from 1.6 to 1.3), whereas the median ratio of Z-10-OH-NT to nortriptyline plasma level did not change significantly. These results are consistent with the known inhibition by perphenazine of the cytochrome P450 2D6 (sparteine/debrisoquine hydroxylase), the major enzyme involved in the oxidative metabolism of nortriptyline, mostly through the formation of E-10-OH-NT. This complex alteration in the metabolism of nortriptyline induced by perphenazine emphasizes the relevance of measuring plasma levels not only of nortriptyline but also of its hydroxymetabolites in older patients who are more likely to be sensitive to their differing cardiovascular, anticholinergic, and cognitive effects.

Aged↗
PubMed1996

Longitudinal effects of nortriptyline on EEG sleep and the likelihood of recurrence in elderly depressed patients.

Our objectives were to determine the effects of nortriptyline and placebo on subjective and EEG sleep measures over 1 year of maintenance therapy in elderly depressed patients and to determine the relationship of such effects to recurrence in nortriptyline or placebo-treated patients during maintenance therapy. EEG and subjective sleep assessments were conducted before and during a maintenance therapy study of patients suffering from major depression. During acute treatment all patients received nortriptyline plus interpersonal psychotherapy (IPT). During maintenance treatment patients were randomly assigned to double-blind treatment in one of four cells: nortriptyline with IPT; nortriptyline with medication clinic (no IPT); placebo with IPT; or placebo with medication clinic. Sleep evaluations were conducted at one point before treatment, one point following remission during continuation nortriptyline/IPT treatment, and at three time points after random assignment to maintenance treatment. The setting was the sleep laboratory of the outpatient depression treatment clinic, and subjects were a convenience sample of media-recruited and clinically referred elderly outpatient depressed patients (n = 72). Complete sleep analyses were conducted for 21 nortriptyline- and 10 placebo-treated patients throughout 1 year of maintenance treatment. The main outcome measures were subjective and EEG sleep measures and the recurrence of major depression. Our results show that nortriptyline acutely and persistently decreased REM sleep, increased phasic REM activity, decreased sleep apnea, and had no effect on periodic limb movements during sleep. Recurrence on maintenance nortriptyline was associated with lower phasic REM activity during early continuation therapy, but EEG sleep measures did not predict recurrence during placebo maintenance therapy. Patients treated with nortriptyline had a lower recurrence rate than those treated with placebo. Better subjective sleep quality and maintenance IPT were associated with a lower rate of recurrence regardless of nortriptyline treatment. It seems that nortriptyline has persistent effects on REM sleep and sleep apnea in elderly depressed patients. Maintenance nortriptyline, maintenance IPT, good subjective sleep quality, and high-phasic REM activity are associated with a reduced likelihood of the recurrence of depression during maintenance therapy.

Aged↗
PubMed1995

Active hydroxymetabolites of antidepressants. Emphasis on E-10-hydroxy-nortriptyline.

Hydroxymetabolites of the antidepressants nortriptyline and desipramine, like the parent drugs, inhibit neuronal uptake of noradrenaline (norepinephrine). In both plasma and cerebrospinal fluid (CSF), the concentrations of the 10-hydroxymetabolites of nortriptyline (10-OH-NT) are usually higher than those of the parent drugs, but there is a pronounced interindividual variation in the plasma concentrations. This shows that during treatment with nortriptyline, hydroxymetabolites exert, at least in some patients, major effects on brain noradrenaline neurons. Hydroxymetabolites of antidepressants are formed by the polymorphic cytochrome P450 enzyme CYP2D6. Nortriptyline is hydroxylated by this enzyme in a highly stereospecific way to the (-)-enantiomer of E-10-OH-NT. Among Caucasians, 7% are poor metabolisers of the CYP2D6 probe drug debrisoquine. These patients will form very little hydroxymetabolite. The affinity of E-10-OH-NT for muscarinic acetylcholine receptors in vitro was only one-eighteenth of the affinity of nortriptyline for these receptors. In healthy individuals, nortriptyline decreased saliva flow to a significantly greater extent than either E-10-OH-NT or placebo. In an ultrarapid hydroxylator of nortriptyline treated with very high doses of nortriptyline, the plasma concentration of unconjugated 10-OH-NT was very high without any sign of anticholinergic adverse effects. These results show that hydroxymetabolites of nortriptyline have much less anticholinergic effect than the parent drug. When racemic E-10-OH-NT per se was given to healthy individuals, the plasma concentration of the (-)-enantiomer was 5-fold higher than that of (+)-E-10-OH-NT. The 2 enantiomers were eliminated in parallel with an elimination half-life of 8 to 10 hours. A combined in vitro and in vivo investigation showed that a mean of 64% of (+)-E-10-OH-NT was glucuronidated in the liver and subsequently eliminated in urine. Of the administered (-)-enantiomer, a mean of 36% was eliminated as glucuronide formed in the intestine and 35% was actively secreted as unchanged form in urine. Plasma protein binding, determined by ultrafiltration, of the (+)- and (-)-enantiomers of E-10-OH-NT was 54 and 69%, respectively, which is less than that of nortriptyline (92%). The concentration of E-10-OH-NT in CSF was 50% of the concentration of unbound in plasma. There seems to be a stereoselective active transport of E-10-OH-NT from the CSF to blood. We administered racemic E-10-OH-NT to 5 patients during a major depressive episode.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Proteins↗
PubMed1988

Electrocardiographic changes with nortriptyline and 10-hydroxynortriptyline in elderly depressed outpatients.

Pharmacokinetic factors may contribute to altered nortriptyline effects in the elderly. Plasma concentrations of nortriptyline's principal metabolite, E-10-hydroxynortriptyline, tend to be greater than nortriptyline, increase with age, and may contribute to cardiotoxicity. Electrocardiogram changes were evaluated in 21 ambulatory, elderly, depressed outpatients who were treated with therapeutic doses of nortriptyline. Resting electrocardiograms were obtained before and after 6 weeks of treatment. Plasma samples were assayed simultaneously for nortriptyline, E-, and Z-10-hydroxynortriptyline. Three subjects developed a first degree atrioventricular block and one developed a right bundle branch block during treatment. Mean daily nortriptyline dose and steady state plasma level in these subjects did not differ from those who did not develop conduction defects, but E-10-hydroxynortriptyline levels were significantly higher. Overall, there were significant correlations between changes in the PR interval and QRS duration with plasma concentrations of nortriptyline, E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline, and the sum of nortriptyline and its 10-hydroxynortriptyline metabolites. Multiple regression analyses suggested that increases in PR interval were associated with increasing nortriptyline concentration, while increases in QRS duration and Q-Tc intervals were associated with increasing Z-10-hydroxynortriptyline concentration. E- and Z-10-hydroxynortriptyline may contribute substantially to the cardiac conduction effects of nortriptyline treatment and may be of particular importance in the elderly.

Aged↗
PubMed1999

Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years.

CONTEXT: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability. OBJECTIVE: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years. DESIGN: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist. SETTING: University-based psychiatric research clinic. PATIENTS: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions. INTERVENTIONS: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22). MAIN OUTCOME MEASURE: Recurrence of major depressive episode. RESULTS: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years. CONCLUSION: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

Adrenergic Uptake Inhibitors↗
PubMed1977

Quantitative determination of amitriptyline and its principal metabolite, nortriptyline, by GLC-chemical ionization mass spectrometry.

A quantitative GLC-mass spectrometry assay was developed for the determination of the tricyclic antidepressant amitriptyline and its desmethyl metabolite (nortriptyline) in human plasma. The assay utilizes selective ion detection to monitor in a GLC effluent the MH+ molecular ions of amitriptyline and nortriptyline generated by isobutane chemical ionization. The procedure, which utilizes deuterated analogs of amitriptyline and nortriptyline as internal standards, requires 1 ml of plasma and can measure 1 ng/ml of amitriptyline and 0.5 ng/ml of nortriptyline. The curves relating the amounts of amitriptyline and nortriptyline added versus the amounts found over a 100-fold range of amitriptyline and nortriptyline concentrations are straight lines with intercepts of approximately zero and slopes of unity. Analyses of plasma samples from three subjects receiving 50 mg of amitriptyline orally, three times a day, gave an average plasma concentration of 115 +/- 42 ng/ml for amitriptyline and 109 +/- 20 ng/ml for nortriptyline. Similar analyses of the plasma of three subjects who had received a single 50-mg oral dose of amitriptyline showed an average maximum plasma concentration of 25 +/- 10 ng/ml for amitriptyline and 10 +/- 4 ng/ml for nortriptyline. Seventy-two hours after adminis-ration, the average plasma amitriptyline and nortriptyline levels were 3 +/- 2 ng/ml, respectively.

Adult↗
PubMed1982

Nortriptyline metabolism in chronic renal failure: metabolite elimination.

Single oral dose kinetics of nortriptyline and of tis two major metabolites, conjugated and unconjugated 20-hydroxynortriptyline, were studied in eight healthy subjects and 15 patients with chronic renal failure, five of whom were being treated with hemodialysis. Nortriptyline kinetics were unaltered, but the elimination of the metabolites was reduced in both groups of patients. In chronic renal failure the excretion of nortriptyline metabolites appeared to be the rate-limiting step in nortriptyline elimination. Three depressed hemodialysis patients were treated with nortriptyline (75 mg at night) for 6 wk. The ratios of the steady-state plasma concentrations of unconjugated 10-hydroxynortriptyline to nortriptyline (0.74 to 2.30) were in the same range as those in a control group of depressed patients with adequate renal function (0.53 to 4.08) who were also receiving nortriptyline. Conjugated 10-hydroxynortriptyline in renal failure patients was slow to reach steady-state concentrations and these were 10 to 20 times as high as those of the control depressed patients. Conjugated 10-hydroxynortriptyline in dialysis fluid during treatment showed that a mean 43 +/- 7% (SD) of the dose was removed by a 10-hr dialysis. Dialysis clearance of conjugated 10-hydroxynortriptyline was 58 +/- 8 (SD) ml min-1, but nortriptyline and unconjugated 10-hydroxynortriptyline were not appreciably removed by dialysis. Hemodialysis is not likely to be of value in the management of acute nortriptyline poisoning.

Adolescent↗
PubMed1986

Effects of smoking on nortriptyline plasma concentrations in depressed patients.

The pharmacokinetic parameters of half-life, volume of distribution, and steady-state nortriptyline plasma concentration normalized to a 100-mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 +/- 33 ng/ml was significantly lower than the nonsmokers' mean value of 158 +/- 35 ng/ml. The mean normalized free plasma concentrations for the smokers of 11.4 +/- 3.5 ng/ml was not different from the nonsmokers' mean concentrations of 11.5 +/- 2.6 ng/ml. The smokers had a slightly higher percentage free drug values of 10.2 +/- 4.0% (p = 0.08) as contrasted to 7.4 +/- 1.5% free nortriptyline for the nonsmokers. The nortriptyline half-life figures for both the free and total drug concentrations did not differ. Multiple linear regression analysis utilizing age, smoking status, sex, liver function, and the presence or absence of enzyme-inducing or -inhibiting drugs as the potential independent variables and percentage free nortriptyline or total nortriptyline concentration as the dependent variable, found that smoking status explained 21% of the variation in the percentage free nortriptyline in the patients and 26% of the variation in the total nortriptyline concentrations. These preliminary data suggest that smokers ideally should be dosed at the lower end of the nortriptyline therapeutic range, whereas nonsmokers should be dosed at the upper end to maximize the antidepressant effect and minimize adverse effects.

Adolescent↗
PubMed1999

Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy.

OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.

Aged↗