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Charles F Reynolds - One of the best experts on this subject based on the ideXlab platform.
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treatment of bereavement related major depressive episodes in later life a controlled study of acute and continuation treatment with Nortriptyline and interpersonal psychotherapy
FOCUS, 2004Co-Authors: Charles F Reynolds, Ellen Frank, James M Perel, Mark D. Miller, Cleon Cornes, Patricia R. Houck, Sati Mazumdar, Mary Amanda Dew, Rona E Pasternak, David J. KupferAbstract: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 double-blind 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 w...
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cyp2d6 genotyping with oligonucleotide microarrays and Nortriptyline concentrations in geriatric depression
Neuropsychopharmacology, 2001Co-Authors: Greer M Murphy, Margaret A Kirshner, Nina Pascoe, William Cheuk, Benoit H Mulsant, Bruce G. Pollock, Charles F ReynoldsAbstract:Recent advances in oligonucleotide microarray technology (“gene chips”) permit rapid screening for DNA sequence variation. The CYP2D6 gene encodes debrisoquine hydroxylase, which metabolizes the antidepressant Nortriptyline and other psychotropic medications. Nortriptyline plasma concentrations were obtained after at least three weeks of treatment in 36 geriatric patients with major depression who were taking a mean of 8.6 other medications besides Nortriptyline. Oligonucleotide microarrays were used to detect 16 CYP2D6 alleles that affect debrisoquine hydroxylase activity. Subjects carrying alleles encoding impaired debrisoquine hydroxylase activity had significantly greater Nortriptyline concentrations and lower Nortriptyline doses than did other subjects. Significant correlations were found between the numbers of alleles encoding decreased metabolism and Nortriptyline plasma concentration, Nortriptyline dose, and Nortriptyline plasma concentration standardized for dose, indicating a gene dosage effect. These results demonstrate that CYP2D6 genotyping on a microarray platform can be used to predict plasma antidepressant concentrations despite advanced patient age and numerous concurrent medications.
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a twelve week double blind randomized comparison of Nortriptyline and paroxetine in older depressed inpatients and outpatients
American Journal of Geriatric Psychiatry, 2001Co-Authors: Benoit H Mulsant, Bruce G. Pollock, Mark D. Miller, Patricia R. Houck, Sati Mazumdar, Robert D Nebes, Robert A Sweet, J A Stack, Salem Bensasi, Charles F ReynoldsAbstract:Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with Nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72±8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with Nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (Nortriptyline: 57% vs. paroxetine: 55%), or the Completer analysis (Nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than Nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.
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a double blind randomized comparison of Nortriptyline plus perphenazine versus Nortriptyline plus placebo in the treatment of psychotic depression in late life
The Journal of Clinical Psychiatry, 2001Co-Authors: Benoit H Mulsant, Bruce G. Pollock, Sati Mazumdar, Amy Begley, Robert A Sweet, Jules Rosen, George S Zubenko, Tracy Flynn, Charles F ReynoldsAbstract:Objective To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression. Method The efficacy of Nortriptyline plus placebo versus Nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on Nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment. Results Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received Nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (Nortriptyline-plus-perphenazine group, 50% vs. Nortriptyline-plus-placebo group, 44%). Conclusion When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life.
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paroxetine versus Nortriptyline in the continuation and maintenance treatment of depression in the elderly
Depression and Anxiety, 2001Co-Authors: Gregory M Bump, Benoit H Mulsant, Bruce G. Pollock, Sati Mazumdar, Mary Amanda Dew, Amy Begley, Charles F ReynoldsAbstract:Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus Nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or Nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; Nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and Nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in Nortriptyline-treated patients. Paroxetine and Nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.
Benoit H Mulsant - One of the best experts on this subject based on the ideXlab platform.
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effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes short term efficacy and adverse effects
Archives of General Psychiatry, 2009Co-Authors: Harold A Sackeim, Benoit H Mulsant, Thomas B Cooper, Joan Prudic, Elaine M Dillingham, Vaughn W Mccall, Peter B Rosenquist, Keith E Isenberg, Keith S GarciaAbstract:Context Medication resistance is the leading indication for use of electroconvulsive therapy (ECT) in major depression. The practice of stopping antidepressant medications prior to ECT derived from studies in the 1960s and 1970s in nonresistant samples. There is also continuing controversy regarding the relative efficacy and adverse effects of right unilateral and bilateral ECT. Objective To test the hypotheses that, compared with placebo, concomitant treatment with nortriptline or venlafaxine during the ECT course enhances short-term efficacy without a meaningful effect on adverse effects and reduces the rate of post-ECT relapse, and to test the hypotheses that high-dose, right-sided, unilateral ECT is equivalent in efficacy to moderate-dosage bilateral ECT and retains advantages with respect to cognitive adverse effects. Design Prospective, randomized, triple-masked, placebo-controlled study conducted from 2001 through 2005. Setting Three university-based hospitals. Patients Of approximately 750 consecutive patients referred for ECT, 319 with a major depressive episode consented, were randomized to pharmacological or ECT treatment conditions, and received at least 1 ECT treatment. Main Outcome Measures Scores on the Hamilton Rating Scale for Depression, remission rate following completion of ECT, and selective measures of cognitive adverse effects. Results Treatment with Nortriptyline enhanced the efficacy and reduced the cognitive adverse effects of ECT relative to placebo. Venlafaxine resulted in a weaker degree of improvement and tended to worsen cognitive adverse effects. High-dosage right unilateral ECT did not differ or was superior to bilateral ECT in efficacy and resulted in less severe amnesia. Conclusions The efficacy of ECT is substantially increased by the addition of an antidepressant medication, but such medications may differ in whether they reduce or increase cognitive adverse effects. High-dose, right-sided, unilateral ECT is at least equivalent to moderate-dosage bilateral ECT in efficacy, but retains advantages with respect to cognitive adverse effects.
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cyp2d6 genotyping with oligonucleotide microarrays and Nortriptyline concentrations in geriatric depression
Neuropsychopharmacology, 2001Co-Authors: Greer M Murphy, Margaret A Kirshner, Nina Pascoe, William Cheuk, Benoit H Mulsant, Bruce G. Pollock, Charles F ReynoldsAbstract:Recent advances in oligonucleotide microarray technology (“gene chips”) permit rapid screening for DNA sequence variation. The CYP2D6 gene encodes debrisoquine hydroxylase, which metabolizes the antidepressant Nortriptyline and other psychotropic medications. Nortriptyline plasma concentrations were obtained after at least three weeks of treatment in 36 geriatric patients with major depression who were taking a mean of 8.6 other medications besides Nortriptyline. Oligonucleotide microarrays were used to detect 16 CYP2D6 alleles that affect debrisoquine hydroxylase activity. Subjects carrying alleles encoding impaired debrisoquine hydroxylase activity had significantly greater Nortriptyline concentrations and lower Nortriptyline doses than did other subjects. Significant correlations were found between the numbers of alleles encoding decreased metabolism and Nortriptyline plasma concentration, Nortriptyline dose, and Nortriptyline plasma concentration standardized for dose, indicating a gene dosage effect. These results demonstrate that CYP2D6 genotyping on a microarray platform can be used to predict plasma antidepressant concentrations despite advanced patient age and numerous concurrent medications.
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a twelve week double blind randomized comparison of Nortriptyline and paroxetine in older depressed inpatients and outpatients
American Journal of Geriatric Psychiatry, 2001Co-Authors: Benoit H Mulsant, Bruce G. Pollock, Mark D. Miller, Patricia R. Houck, Sati Mazumdar, Robert D Nebes, Robert A Sweet, J A Stack, Salem Bensasi, Charles F ReynoldsAbstract:Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with Nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72±8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with Nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (Nortriptyline: 57% vs. paroxetine: 55%), or the Completer analysis (Nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than Nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.
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a double blind randomized comparison of Nortriptyline plus perphenazine versus Nortriptyline plus placebo in the treatment of psychotic depression in late life
The Journal of Clinical Psychiatry, 2001Co-Authors: Benoit H Mulsant, Bruce G. Pollock, Sati Mazumdar, Amy Begley, Robert A Sweet, Jules Rosen, George S Zubenko, Tracy Flynn, Charles F ReynoldsAbstract:Objective To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression. Method The efficacy of Nortriptyline plus placebo versus Nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on Nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment. Results Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received Nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (Nortriptyline-plus-perphenazine group, 50% vs. Nortriptyline-plus-placebo group, 44%). Conclusion When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life.
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continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy a randomized controlled trial
JAMA, 2001Co-Authors: Harold A Sackeim, Benoit H Mulsant, Roger F Haskett, Michael E Thase, John J Mann, Helen M Pettinati, Robert M Greenberg, Raymond R Crowe, Thomas B Cooper, Joan PrudicAbstract:ContextElectroconvulsive therapy (ECT) is highly effective for treatment of major depression, but naturalistic studies show a high rate of relapse after discontinuation of ECT.ObjectiveTo determine the efficacy of continuation pharmacotherapy with Nortriptyline hydrochloride or combination Nortriptyline and lithium carbonate in preventing post-ECT relapse.DesignRandomized, double-blind, placebo-controlled trial conducted from 1993 to 1998, stratified by medication resistance or presence of psychotic depression in the index episode.SettingTwo university-based hospitals and 1 private psychiatric hospital.PatientsOf 290 patients with unipolar major depression recruited through clinical referral who completed an open ECT treatment phase, 159 patients met remitter criteria; 84 remitting patients were eligible and agreed to participate in the continuation study.InterventionsPatients were randomly assigned to receive continuation treatment for 24 weeks with placebo (n = 29), Nortriptyline (target steady-state level, 75-125 ng/mL) (n = 27), or combination Nortriptyline and lithium (target steady-state level, 0.5-0.9 mEq/L) (n = 28).Main Outcome MeasureRelapse of major depressive episode, compared among the 3 continuation groups.ResultsNortriptyline-lithium combination therapy had a marked advantage in time to relapse, superior to both placebo and Nortriptyline alone. Over the 24-week trial, the relapse rate for placebo was 84% (95% confidence interval [CI], 70%-99%); for Nortriptyline, 60% (95% CI, 41%-79%); and for Nortriptyline-lithium, 39% (95% CI, 19%-59%). All but 1 instance of relapse with Nortriptyline-lithium occurred within 5 weeks of ECT termination, while relapse continued throughout treatment with placebo or Nortriptyline alone. Medication-resistant patients, female patients, and those with more severe depressive symptoms following ECT had more rapid relapse.ConclusionsOur study indicates that without active treatment, virtually all remitted patients relapse within 6 months of stopping ECT. Monotherapy with Nortriptyline has limited efficacy. The combination of Nortriptyline and lithium is more effective, but the relapse rate is still high, particularly during the first month of continuation therapy.
E J Wagena - One of the best experts on this subject based on the ideXlab platform.
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genetic variants in the serotonin transporter influence the efficacy of bupropion and Nortriptyline in smoking cessation
Addiction, 2012Co-Authors: E J Wagena, C P Van Schayck, Marieke Quaak, Dirkje S Postma, Frederik J Van SchootenAbstract:Aims We investigated whether variants in the serotonin transporter gene (SLC6A4) influence smoking cessation rates using antidepressant therapy (i.e. bupropion and Nortriptyline). Design Pharmacogenetic (secondary) analysis of a randomized, placebo-controlled efficacy trial of bupropion and Nortriptyline for smoking cessation. Setting Single-centre study, Maastricht University, the Netherlands. Participants A total of 214 of 255 (84%) current daily smokers participating in a randomized controlled efficacy trial. Measurements Subjects were genotyped for three functional variants in SLC6A4 (5-HTTLPR, STin2, rs25531). Primary outcome measures were prolonged abstinence from weeks 4-12, 4-26 and 4-52. Secondary outcome measures included 7-day point prevalence abstinence at weeks 4, 12, 26 and 52. Findings Carriers of the 5-HTTLPR high-activity L-variant had higher prolonged cessation rates with bupropion than placebo [ odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.01-2.05, P = 0.04]. Combining the three variants resulted in increased prolonged cessation rates for both bupropion and Nortriptyline among carriers of four to five high-activity variants (bupropion: OR = 2.00, 95% CI = 1.21-3.29, P = 0.01; Nortriptyline: OR = 1.91, 95% CI = 1.02-3.56, P = 0.04). Similar results were found for point prevalence abstinence. Conclusions Bupropion and Nortriptyline seem to be more effective in smoking cessation among SLC6A4 high-activity variant carriers, probably by blocking the increased serotonin transporter activity, thereby increasing serotonin levels. Prospective studies have to assess if this can improve cessation rates when treatment is targeted at individuals based on their genotypes.
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efficacy of bupropion and Nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease
JAMA Internal Medicine, 2005Co-Authors: E J Wagena, P G Knipschild, Marcus J H Huibers, Emiel F M Wouters, C P Van SchayckAbstract:Background The observations that smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD. No clinical trial has studied the efficacy of bupropion hydrochloride and Nortriptyline hydrochloride for smoking cessation in this patient population, to our knowledge. Methods In a placebo-controlled double-dummy randomized trial, 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion (bupropion SR) (150 mg twice daily) or Nortriptyline (75 mg once daily) for 12 weeks. All patients received smoking cessation counseling. The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date. Results The use of bupropion SR and Nortriptyline resulted in higher prolonged abstinence rates compared with placebo, although only the difference between bupropion SR and placebo was statistically significant (differences with placebo, 13.1% [95% confidence interval, 1.2%-25.1%] for bupropion SR and 10.2% [95% confidence interval, −1.7% to 22.2%] for Nortriptyline). In patients with COPD, bupropion SR and Nortriptyline seem efficacious in achieving prolonged abstinence (differences with placebo, 18.9% [95% confidence interval, 3.6%-34.2%] for bupropion SR and 12.9% [95% confidence interval, −0.8% to 26.4%] for Nortriptyline). In participants at risk for COPD, no statistically significant differences with placebo in prolonged abstinence rates were found. Conclusions Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative.
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should Nortriptyline be used as a first line aid to help smokers quit results from a systematic review and meta analysis
Addiction, 2005Co-Authors: E J Wagena, P G Knipschild, Maurice P ZeegersAbstract:Objectives The objective of this paper is to evaluate the efficacy of Nortriptyline for smoking cessation compared to placebo and bupropion sustained release. Data sources Randomized trials were identified by (1) checking electronic and (2) online publicly accessible registers of clinical trials; (3) searching references of identified studies and screening abstract books of conferences and symposia, and (4) personal communication with the first authors of identified papers. Review methods We included randomized trials in which Nortriptyline was compared to placebo or bupropion hydrochloride SR. The main clinical outcome measure was (at least) 6-month prolonged abstinence, confirmed with a biochemical test. To investigate the efficacy of Nortriptyline in time, we calculated the percentage of smokers who relapsed in time. Results We identified five randomized trials, including 861 smokers. Compared to placebo medication, Nortriptyline resulted in significantly higher prolonged abstinence rates after at least 6 months [relative risk (RR) = 2.4, 95% CI 1.7–3.6; RD = 0.11, 95% CI 0.07–0.15]. The difference in efficacy between Nortriptyline and placebo was highest in the first months after the target quit date. However, the number of people who remained abstinent decreased substantially and significantly faster over time in the Nortriptyline group. Although bupropion resulted in higher abstinence rates compared with Nortriptyline, the difference was not statistically significant (RR = 1.7, 95% CI 0.7–4.1). Conclusion This systematic review and meta-analysis shows that the use of Nortriptyline for smoking cessation resulted in higher prolonged abstinence rates after at least 6 months compared to placebo treatment. Furthermore, the use of Nortriptyline for smoking cessation is well tolerated and safe. As a result, we believe health care professionals should be recommended to prescribe Nortriptyline as a first-line therapy for smoking cessation, also because of the much lower cost of Nortriptyline compared to bupropion SR.
Peter R. Joyce - One of the best experts on this subject based on the ideXlab platform.
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age dependent antidepressant pharmacogenomics polymorphisms of the serotonin transporter and g protein β3 subunit as predictors of response to fluoxetine and Nortriptyline
The International Journal of Neuropsychopharmacology, 2003Co-Authors: Peter R. Joyce, Roger T. Mulder, Suzanne E. Luty, Janice M. Mckenzie, Allison L Miller, Geraldine R Rogers, Martin A KennedyAbstract:In 169 depressed patients randomized to treatment with either fluoxetine or Nortriptyline, we examined whether polymorphisms of the serotonin transporter and the G protein β 3 subunit influenced response to these antidepressants. For depressed patients under the age of 25 yr the T allele of the G protein β 3 subunit was associated with a markedly poorer response to Nortriptyline, while serotonin transporter polymorphisms did not predict antidepressant response. However, in patients 25 yr or older, the G protein β 3 polymorphisms did not predict antidepressant response, while the s,s genotype of the serotonin transporter was associated with a poorer response to both fluoxetine and Nortriptyline. These differential pharmacogenetic predictors of antidepressant response by age, may provide clues to understanding the discontinuities in pharmacological responsiveness of child/adolescent and adult depressive disorders.
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A differential response to Nortriptyline and fluoxetine in melancholic depression: the importance of age and gender.
Acta psychiatrica Scandinavica, 2003Co-Authors: Peter R. Joyce, Roger T. Mulder, Suzanne E. Luty, Janice M. Mckenzie, A. M. RaeAbstract:Objective: To consider the impact of age and gender on the antidepressant response to Nortriptyline and fluoxetine in melancholic depression. Method: Of 191 depressed patients, 113 met study criteria for melancholia. All patients were randomized to receive either fluoxetine or Nortriptyline. Response rates, defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis, were examined by age, and by age and gender. Results: Melancholic depressed patients 40 years or older, especially men, had a markedly superior response to Nortriptyline compared with fluoxetine. Conversely, melancholic depressed patients, age18–24 years, especially women, had a markedly superior response to fluoxetine. Conclusion: Age and gender appear to be critical variables in understanding differential antidepressant responses to tricyclic antidepressants and selective serotonin reuptake inhibitors in melancholic depression.
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a common p glycoprotein polymorphism is associated with Nortriptyline induced postural hypotension in patients treated for major depression
Pharmacogenomics Journal, 2002Co-Authors: Rebecca L Roberts, Peter R. Joyce, Roger T. Mulder, Evan J Begg, Martin A KennedyAbstract:The multi-drug resistance gene ABCB1 (or MDR1) encodes a P-glycoprotein (P-gp) that regulates passage of many substances across the blood–brain barrier. The antidepressant amitriptyline and its metabolites (including Nortriptyline) are substrates for P-gp, and in mice lacking P-gp, penetration of amitriptyline, but not fluoxetine, into the brain is enhanced. We reasoned that polymorphic variation of P-gp may contribute to differing responses of patients to antidepressant drugs. A single nucleotide polymorphism (SNP) of ABCB1 (3435C>T) was recently correlated with expression levels and in vivo function of P-gp. We examined this SNP in patients with major depression enrolled in a randomized antidepressant treatment trial of Nortriptyline and fluoxetine, and observed a significant association between Nortriptyline-induced postural hypotension and 3435C>T (χ2 = 6.78, df = 2, P = 0.034). Our results suggest that homozygosity for 3435T alleles of ABCB1 is a risk factor for occurrence of Nortriptyline-induced postural hypotension (OR = 1.37, P = 0.042, 95% CI 1.01–1.86).
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patterns and predictors of remission response and recovery in major depression treated with fluoxetine or Nortriptyline
Australian and New Zealand Journal of Psychiatry, 2001Co-Authors: Peter R. Joyce, Suzanne E. Luty, Janice M. Mckenzie, Rogert T Mulder, Patrick F Sullivan, Robyn M Abbott, Isobel StevensAbstract: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 or Nortriptyline. 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 th...
Andrew A Nierenberg - One of the best experts on this subject based on the ideXlab platform.
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psychiatric comorbidity as a predictor of clinical response to Nortriptyline in treatment resistant major depressive disorder
The Journal of Clinical Psychiatry, 2003Co-Authors: George I Papakostas, Timothy Petersen, Jonathan E Alpert, Maurizio Fava, Amy Farabaugh, Jessica L Murakami, Joel A Pava, Andrew A NierenbergAbstract:BACKGROUND A number of studies of major depressive disorder suggest that psychiatric co-morbidity may contribute to treatment resistance. The purpose of this study was to test whether the presence of comorbid Axis I and Axis II disorders predicts clinical response to an open trial of nor-triptyline among patients with treatment-resistant depression. METHOD Ninety-two outpatients with treatment-resistant DSM-III-R major depressive disorder were enrolled in a 6-week open trial of nor-triptyline (Nov. 1992-Jan. 1999). The presence of comorbid Axis I and Axis II disorders was established at baseline with the use of the Structured Clinical Interview for DSM-III-R. Chi-square analyses were used to test Axis I or Axis II co-morbid conditions as a predictor of clinical response to Nortriptyline. RESULTS Thirty-nine patients (42.4%) responded to Nortriptyline. The presence of avoidant personality disorder (p <.01) predicted poorer response to Nortriptyline. The response rate was 16.7% for patients with and 48.6% for patients without comorbid avoidant personality disorder. No other comorbid diagnoses were found to predict clinical response in a statistically significant manner. CONCLUSION The presence of avoidant personality disorder conferred a poorer prognosis in treatment-resistant depression patients treated with Nortriptyline.
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Nortriptyline for treatment resistant depression
The Journal of Clinical Psychiatry, 2003Co-Authors: Andrew A Nierenberg, George I Papakostas, Timothy Petersen, Karen E Kelly, Brian M Iacoviello, John J Worthington, Joyce Tedlow, Jonathan E Alpert, Maurizio FavaAbstract:Background Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of Nortriptyline for patients with treatment-resistant major depression. Method 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with Nortriptyline for 6 weeks. Patients were titrated up to full target doses of Nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. Results Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of Nortriptyline. Over a third of patients were unable to complete the trial. Conclusion Nortriptyline was effective for over a third of patients with treatment-resistant depression, and Nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.