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PubMed1998

Time course of enzyme induction in humans: effect of pentobarbital on nortriptyline metabolism.

To study the effect of induction we gave six male volunteers 10 mg nortriptyline three times a day for 4 weeks and 0.2 gm pentobarbital on days 8 to 21. Plasma and urinary levels of nortriptyline and metabolites were measured. The rate and extent of induction of the enzyme(s) were estimated by a model with use of nortriptyline concentrations. There was a marked decrease of nortriptyline levels after 2 days of pentobarbital treatment. Total clearance of nortriptyline increased more than twofold (range, 1.6-fold to 4.1-fold). Apparent metabolic clearance by 10-hydroxylation increased markedly. The decrease in nortriptyline levels was more rapid than the increase after pentobarbital cessation, fitting with the theory of the model. The induction of nortriptyline metabolism is probably mainly the result of an increase in a non-CYP 2D6 P450 isozyme, possibly CYP 3A4 or a CYP 2C form. More knowledge of induction characteristics of drugs should lead to better predictions of decreased effects and appearance of adverse effects. The kinetic model used for analysis of our data could then be useful.

Adrenergic Uptake Inhibitors↗

PubMed1998

Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes.

OBJECTIVES: To study the impact of the CYP2D6*10 allele on the disposition of nortriptyline in Chinese subjects. METHODS: A single dose of 25 mg nortriptyline was given orally to 15 healthy Chinese volunteers who were classified as extensive metabolizers after phenotyping with debrisoquin (INN, debrisoquine) and who were genotyped by allele-specific polymerase chain reaction. Five subjects were homozygous for CYP2D6*1, 5 subjects were homozygous for CYP2D6*10, and 5 subjects were heterozygous for these 2 alleles. Plasma concentrations of nortriptyline and its main metabolite 10-hydroxynortriptyline were measured by liquid chromatography-mass spectrometry, and the pharmacokinetics were studied during 168 hours after the dose. RESULTS: Subjects who were homozygous for CYP2D6*10 had significantly higher total areas under the plasma concentration-time curve (AUC), lower apparent oral clearances, and longer mean plasma half-life of nortriptyline than subjects in the CYP2D6*1/*1 and the heterozygous groups. For 10-hydroxynortriptyline, the AUC was lower and the plasma half-life was longer in subjects who were homozygous for CYP2D6*10 than in subjects in the other 2 groups. CONCLUSION: The CYP2D6*10 allele in Chinese subjects was associated with significantly higher plasma levels of nortriptyline compared with the CYP2D6*1 allele because of an impaired metabolism of nortriptyline to 10-hydroxynortriptyline, particularly in the subjects with the CYP2D6*10/*10 genotype. The results suggest that genotyping of CYP2D6 may be a useful tool in predicting the pharmacokinetics of nortriptyline.

Adult↗

PubMed2000

Comparison of UV spectrophotometric and LC methods for the determination of nortriptyline hydrochloride in polysorbate 80 based oil/water (o/w) microemulsions.

A new rapid, reliable and specific UV spectrophotometric method was developed for the determination of nortriptyline hydrochloride formulated into o/w microemulsions. The UV spectra of nortriptyline standard solution in methanol and placebo (microemulsion without nortriptyline) were recorded over the wavelength range 200-600 nm and the spectra for placebo and nortriptyline loaded microemulsion were recorded over the range 260-400 nm in order to determine the overlapping that might appears, and hence to set the wavelength that could be used for the quantitative analysis. This method was validated and compared with a liquid chromatography (LC) procedure used for the quantitative analysis of the drug. Both methods showed excellent precision and accuracy with RSD values of 2.37 and 1.41%, respectively, for the LC method, and values of 1.24 and 2.88%, respectively, for the UV spectrophotometric method. The established linearity range was 10-50 microg ml(-1) (r2 = 0.9985) and 20-60 microg ml(-1) (r2 = 0.9979) for the HPLC and UV spectrophotometric methods respectively. The recoveries of nortriptyline from spiked placebos were > 95% for both methods over the linear range. The methods have been successfully used for determining the nortriptyline content of microemulsions and for evaluating the chemical stability of the drug in nortriptyline-loaded microemulsions.

Antidepressive Agents, Tricyclic↗

PubMed2002

Patterns and predictors of remission, response and recovery in major depression treated with fluoxetine or nortriptyline.

OBJECTIVE: The first objective of this paper was to describe the pattern of remission, response and recovery in patients with major depression who were randomised for treatment with fluoxetine ornortriptyline. The second objective was to report on the demographic and diagnostic predictors of the response and recovery in these depressed patients. METHOD: One hundred and ninety-five patients with major depression were recruited for this outpatient study. After a detailed clinical and neurobiological evaluation patients were randomized to receive either fluoxetine or nortiptyline as an initial antidepressant treatment. RESULTS: Of the 195 depressed patients randomised to treatment,154 completed an adequate 6-week trial of either fluoxetine or nortriptyline as their initial antidepressant. Of the 41 patients who did not complete an adequate trial the dropout rate was higher on those randomized to nortriptyline (p = 0.02). There was also an important interaction of drug and gender in determining dropouts in that women did not complete an adequate trial with nortriptyline and men did not complete an adequate trial with fluoxetine (p = 0.002). Of the 154 patients who completed an adequate 6-week antidepressant trial there were no significant differences in 6-week measures of depression severity or of percentage improvement. However, if we use an intention to treat analysis and dichotomise outcomes into response,remission or recovery; then recovery rates were significantly higher with fluoxetine than nortriptyline (p = 0.005). Using an intention to treat analysis fluoxetine was superior tonortriptyline in women, in those less than 25-years old, and in those with atypical depression. Independent of drug, those with chronic depressions had a poorer outcome. CONCLUSION: In this sample of depressed patients randomized tonortriptyline or fluoxetine the change in depressive symptoms over 6 weeks were comparable between fluoxetine and nortriptyline. However,when we look at the more clinically important variable of recovery then fluoxetine was superior to nortriptyline. Predictors of a poorer response to nortriptyline were gender, young age and atypical depression. The results challenge traditional beliefs that selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressant have comparable efficacy.

Adult↗

PubMed2005

Nortriptyline for smoking cessation: a review.

This article reviews the efficacy of nortriptyline for smoking cessation based on a meta-analysis of the Cochrane Library. Six placebo-controlled trials have shown nortriptyline (75-100 mg) doubles quit rates (OR = 2.1). Between 4% and 12% of smokers dropped out because of adverse events, but no serious adverse events occurred. The efficacy of nortriptyline did not appear to be related to its antidepressant actions. Nortriptyline is an efficacious aid to smoking cessation with a magnitude of effect similar to that for bupropion and nicotine replacement therapies. Whether nortriptyline produces serious side effects at these doses in healthy, nondepressed smokers remains unclear because it has been tested in only 500 smokers. The finding that nortriptyline and bupropion are effective for smoking cessation but that selective serotonin-reuptake inhibitors are not suggests that dopaminergic or adrenergic, but not serotonergic, activity is important for cessation efficacy. Until further studies can verify a low incidence of significant adverse events, nortriptyline should be a second-line treatment for smoking cessation.

Antidepressive Agents, Tricyclic↗

PubMedDate not supplied

Selective determination of amitriptyline and nortriptyline in human plasma by HPLC with ultraviolet and particle beam mass spectrometry.

A selective, sensitive, and reliable method was devised to determine concentrations of amitriptyline and its major metabolite, nortriptyline, in human plasma using high-performance liquid chromatography (HPLC) combined with UV and particle beam mass spectrometry (PBMS). Amitriptyline and nortriptyline were effectively extracted in a three-step solvent extraction procedure. Imipramine was used as the internal standard (IS). Amitriptyline, nortriptyline, and the IS were clearly separated by HPLC on a silica column with the mobile phase of acetonitrile-0.1 M ammonium acetate (94:6, v/v). The calibration curves were linear in the concentration range of 10-1000 ng/g for both compounds with UV and PBMS detections. The lower limits of detection were 5 ng/g for amitriptyline and 10 ng/g for nortriptyline with UV detection and 2 ng/g for amitriptyline and 5 ng/g for nortriptyline with PBMS detection. The absolute recoveries were 58% for amitriptyline and 47% for nortriptyline at a concentration of 50 ng/g. This method proved most useful in accurately identifying amitriptyline and nortriptyline in tissues from an autopsied individual.

Acetates↗

PubMedDate not supplied

Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial.

OBJECTIVE: Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment. This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome. METHOD: Sixty-eight diabetic patients with poor glycemic control, 28 of whom had active major depression (DSM-IIIR), completed a randomized, placebo-controlled, double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels (50-150 ng/ml). Depression improvement was determined with the Beck Depression Inventory; glucose control was measured by glycated hemoglobin levels. Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory. RESULTS: The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo (-10.2 vs -5.8, p = .03). Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects (p = .5). However, path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin. These findings were not explained by the relationships of nortriptyline treatment to weight change (r = -0.21, p = .31) or depression improvement to compliance with the protocol for self-monitoring of blood glucose (r = 0.01, p = .97). CONCLUSIONS: Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect. Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control, suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome.

Adult↗

PubMed1981

The pharmacokinetics of nortriptyline in patients with chronic renal failure.

1 The pharmacokinetics of single oral doses of nortriptyline were studied in twenty patients with chronic renal failure, eight of whom were receiving treatment with haemodialysis. 2 The median nortriptyline half-life was 25.2 h (range 14.5-140.0 h) and the median nortriptyline clearance was 32.3 l/h (range 8.1-122.0 l/h). 3 No differences were observed between the dialysed and non-dialysed groups. 4 Comparisons of nortriptyline half-life and clearance between the patients and groups of physically healthy subjects revealed no significant differences. 5 There was no significant linear correlation between age and either of these measurements. In the twelve patients not receiving haemodialysis there was no correlation between nortriptyline clearance and glomerular filtration rate. 6 Chronic renal failure is not associated with a significant alteration in nortriptyline metabolism as measured by its half-life or clearance, but the drug should nonetheless be used with caution, and monitored whenever possible. However, the marked inter-individual differences observed in nortriptyline half-life and clearance in patients with chronic renal failure may not be solely responsible for their unpredictable response to tricyclic antidepressant therapy, and other possible contributory factors are discussed.

Adolescent↗

PubMed1977

Plasma nortriptyline and cardiac responses in young and old rats.

1. The relationship between plasma concentrations and cardiac effects of nortriptyline was studied in anaesthetized young and old rats. 2. Nortriptyline was administered by two consecutive intravenous infusions which resulted in a peak plasma concentration followed by steady state values. Increasing infusion rates were followed by proportional increases in the drug plasma concentrations ranging from 0.15 to 6.0 microgram/ml. 3. In young rats, nortriptyline induced an increase in the heart rate, a right rotation of the electrical axis and a prolongation of the PQ interval. Heart rate changes were not correlated with nortriptyline plasma concentrations, while significant correlations were found for the other two parameters. Plasma concentrations inducing 20% increase of the PQ interval and 40 degrees rotation of the electrical axis were 1.65 microgram/ml respectively. Arrhythmias occurred at concentrations higher than 5.2 microgram/ml. 4. Nortriptyline caused more severe cardiac effects in old than in young animals. However, plasma concentrations of nortriptyline in old rats were two to five times higher than those found in young rats at similar infusion rates. A higher concentration of the drug at its sites of action seems to be responsible for the more severe cardiac toxicity of nortriptyline observed in old rats.

Aging↗

PubMed1987

Plasma levels and effects of nortriptyline in geriatric depressed patients.

Pharmacokinetic, therapeutic effects, and side effects of nortriptyline were studied in geriatric depressed patients treated with a standard dose of 150 mg/day. Plasma levels and elimination half-life of nortriptyline were no different in geriatric patients than younger patients. The antidepressant therapeutic effects of nortriptyline appeared to be similar in geriatric patients as in younger depressed patients. Geriatric patients experienced few subjective side effects of nortriptyline. Overall, the drug produced no clinically significant changes in several parameters of the EKG, and no geriatric patient experienced tachycardia on nortriptyline. Nortriptyline did induce significant orthostatic hypotension in the systolic component, but not in the diastolic component. However, the orthostatic hypotension produced by nortriptyline was not greater in geriatric patients than in younger patients treated with the same dose.

Age Factors↗

PubMed1999

Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease.

OBJECTIVE: This study compared the efficacy, tolerability, and safety of paroxetine and nortriptyline in depressed patients with ischemic heart disease. METHOD: After a 2-week, single-blind placebo lead-in phase, 81 outpatients with DSM-III-R-defined nonpsychotic unipolar major depression and ischemic heart disease were randomly assigned to double-blind treatment with paroxetine or nortriptyline for 6 weeks. Paroxetine was administered at a fixed-flexible dose of 20-30 mg/day. Nortriptyline dose was adjusted with the use of blood-level monitoring to reach a plasma concentration of 50-150 ng/ml. RESULTS: Twenty-seven of the 41 patients who started treatment with paroxetine and 29 of the 40 patients who started treatment with nortriptyline had an improvement of at least 50% in their Hamilton Depression Rating Scale scores. Significantly more patients taking nortriptyline discontinued treatment prematurely (35% versus 10%), and more patients taking nortriptyline had adverse events resulting in termination (25% versus 5%). CONCLUSIONS: Both treatments were efficacious. Sixty-three percent of all patients improved at least 50%, and of these, 90% met the criteria for remission. Paroxetine was better tolerated than nortriptyline and less likely to produce cardiovascular side effects.

Adult↗

PubMed2000

Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study.

OBJECTIVE: This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke. METHOD: A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind randomized study comparing nortriptyline, fluoxetine, and placebo over 12 weeks of treatment. The majority of patients were recruited from a rehabilitation hospital in Des Moines, Iowa, but other enrollment sites were also used. Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression. Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks. Response to treatment of depression for individual patients was defined as a greater-than-50% reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression. Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial, compared with patients treated with placebo, on measures of impairment in activities of daily living and levels of cognitive and social functioning. RESULTS: Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression, in improving anxiety symptoms, and in improving recovery of activities of daily living as measured by the Functional Independence Measure. There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients. Fluoxetine in increasing doses of 10-40 mg/day led to an average weight loss of 15. 1 pounds (8% of initial body weight) over 12 weeks of treatment that was not seen with nortriptyline or placebo. CONCLUSIONS: Given the doses of medication used in this study, nortriptyline was superior to fluoxetine in the treatment of poststroke depression. Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients, alternative measurement scales, or the optimal time of treatment.

Activities of Daily Living↗

PubMed2003

Thyroid indices and response to fluoxetine and nortriptyline in major depression.

We investigated: (i) the status of thyroid hormones and their clinical correlates in patients with major depression; (ii) changes in thyroid hormone status after treatment with fluoxetine versus nortriptyline; and (iii) whether blunted thyrotropin-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) challenge predicts improvement after 6 weeks of fluoxetine versus nortriptyline treatment. Patients with major depression entering a treatment trial were assessed with the Structured Clinical Interview for DSM-III-R and were rated on the Montgomery-Asberg Depression Rating Scale (MADRS). Blood samples were taken for TSH, thyroxine (T4) and free thyroxine (FT4) measurement, and the maximum TSH response (deltamaxTSH) to a TRH challenge test was undertaken. Patients were then randomly assigned to receive fluoxetine or nortriptyline for six weeks. At 6 weeks, patients repeated the thyroid hormone assessment and completed the MADRS. Mean concentrations of TSH, T4, FT4 and deltamaxTSH were within reference ranges. T4 and FT4 levels decreased significantly after treatment in responders, but not in nonresponders. After treatment, deltamaxTSH concentrations decreased significantly in patients who responded to fluoxetine, and increased in patients who responded to nortriptyline. Patients with deltamaxTSH blunting at pretreatment were more likely to be male, to have higher MADRS scores and have a history of alcohol and drug dependence. Patients with a pretreatment deltamaxTSH of < 3.0 microm/ml showed greater improvement on the MADRS when treated with fluoxetine than if treated with nortriptyline. We observed a decrease in T4 and FT4 in responders to treatment with fluoxetine or nortriptyline. Positive relationships between deltamaxTSH blunting and alcohol and drug abuse and severity of depression were found. Patients with blunted deltamaxTSH responded better to fluoxetine than to nortriptyline. It is suggested that a blunted DmaxTSH may reflect a predominantly serotonergic disturbance in this group of patients with major depression.

Adolescent↗

PubMed2002

Stopping smoking: a prospective, randomized, double-blind study comparing nortriptyline to placebo.

OBJECTIVE: The administration of antidepressant drugs was shown to positively affect the rate of smoking cessation. This study evaluates the efficacy of nortriptyline in an antismoking program. METHODS: A possible randomized double-blind study that included 144 patients who were randomized to receive nortriptyline, 75 mg/d (68 patients), or placebo (76 patients), during 6 consecutive weeks. All patients attended behavioral group orientation for 5 weeks. The rate of success, complications, adherence to the regime, and factors of pretreatment prognosis were evaluated (multivariate analysis). RESULTS: The groups were balanced in relation to the characteristics of the patients on entering the study. Patients receiving nortriptyline showed significantly higher cessation rate (55.9%) compared to the group receiving placebo (23.3%; p < 0.001). In a univariate analysis on prognosis factors influencing the rate of cessation in our study, the Fagerström test results (p = 0.005) and nortriptyline (p < 0.001) were identified. Logistic regression showed that a Fagerström test score of < 7 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.47 to 6.7; p = 0.003) and nortriptyline use (OR, 4.1; 95% CI, 2 to 8.3; p < 0.001) were independent factors impacting the rate of success for smoking cessation. No significant complications were observed in the nortriptyline group. CONCLUSION: This study showed that nortriptyline significantly increases the smoking cessation rate in chronic smokers, as compared to the placebo group, without any significant side effects.

Adult↗

PubMedDate not supplied

Two prospective dosing methods for nortriptyline.

This study compared two prospective pharmacokinetic dosing methods to predict steady-state concentrations of nortriptyline. One method required multiple determinations of the nortriptyline plasma concentration to estimate the drug's steady-state concentration. The second method required a single nortriptyline concentration drawn at a fixed time, preferably 36 hours, following a nortriptyline test dose. The 36-hour nortriptyline plasma concentrations (NTP 36h) were substituted into the straight-line equation of Cssav = 17.2 + 3.74 (NTP 36h), where Cssav is the average steady-state concentration for a 100 mg/day dose of nortriptyline. No differences were noted between the observed steady-state nortriptyline concentration of 121 +/- 19 ng/ml, the 36-hour single-point prediction mean concentration of 121 +/- 21 ng/ml, or the multiple-point prediction mean concentration of 122 +/- 19 ng/ml. Because of the similar findings between the two methods, the clinical advantages and disadvantages of each kinetic approach are discussed to put these prospective dosing protocols into their proper perspective.

Adult↗

PubMed1990

Relationship of hydroxynortriptyline to nortriptyline concentration and creatinine clearance in depressed elderly outpatients.

Plasma concentration of E-10-hydroxynortriptyline is increased in the elderly and may be related to both renal clearance of hydroxynortriptyline and rate of liver hydroxylation of nortriptyline. In 25 ambulatory, depressed elderly outpatients treated with therapeutic doses of nortriptyline, relationships among plasma levels of nortriptyline and E-10-hydroxynortriptyline, and an estimate of creatinine clearance were examined. Plasma levels of E-10-hydroxynortriptyline (corrected for varying dosage) were significantly correlated with age and inversely correlated (r = -0.50) with creatinine clearance but not with notriptyline or Z-10-hydroxynortriptyline concentration. E-10-hydroxynortriptyline concentration was about 5 1/2 times that of Z-10-hydroxynortriptyline. By best subsets multiple regression analyses, the ratio of E-10-hydroxynortriptyline to nortriptyline level was best predicted by plasma nortriptyline concentration, creatinine clearance, and age, all of which accounted for 63% of the variance. These results corroborate and extend previous findings in elderly inpatients in whom creatinine clearance was measured directly. In addition, age had an effect on E-10-hydroxynortriptyline independently of creatinine clearance. Since E-10-hydroxynortriptyline concentration has been related to both therapeutic efficacy and toxicity during nortriptyline treatment, it may be important to assess nortriptyline hydroxymetabolites in elderly patients and in those with renal insufficiency.

Aged↗

PubMed1977

A comparison study of amitriptyline and nortriptyline with plasma levels.

Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptyline-treated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = -0.54, P less than .025) and positive in the nortriptyline-treated patients (r = -0.49, P less than .05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P less than .001), Zung Score (P less than .01), and percent recovered (P less than .001), than those above or below the therapeutic range.

Administration, Oral↗

PubMed1998

Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking.

BACKGROUND: A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence. METHODS: This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date. RESULTS: Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men. CONCLUSIONS: Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.

Adult↗