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Biomedical subjects

Susan G Kornstein

Publications and source records attributed to Susan G Kornstein.

At least 19 recordsLinked to original sources
PubMed2006

Duloxetine in the treatment of major depressive disorder: comparisons of safety and tolerability in male and female patients.

BACKGROUND: While some studies have suggested sex differences in the efficacy of antidepressant medications, there have been few investigations into potential sex differences related to safety and/or tolerability. Pooled data from double-blind, placebo-controlled studies were utilized to assess the safety and tolerability of duloxetine in the treatment of major depressive disorder (MDD) in male and female patients. METHODS: Safety data were pooled from seven double-blind, placebo-controlled clinical trials of duloxetine. Patients (aged >or=18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day, male: N=318, female: N=578) or placebo (male: N=242, female: N=484) for up to 9 weeks. Safety was assessed using discontinuation rates, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory analyses. RESULTS: Discontinuation rates due to adverse events among duloxetine-treated patients were 18.6% for males and 13.5% for females. The most common treatment-emergent adverse events in both male and female patients included nausea, headache, dry mouth, diarrhea and constipation. The only event occurring at significantly different rates in male and female patients was nausea (Breslow Day p-value=0.008), and the significant difference was driven by a placebo nausea rate that was almost three times greater in females compared with males. No significant differential sex effects were found for pulse, blood pressure or weight. No laboratory analyte had an incidence of abnormal high or low values that differed significantly between male and female patients. LIMITATIONS: This was a post-hoc analysis of pooled data from acute phase clinical trials. Plasma concentrations of duloxetine were not obtained. Adverse event rates were based on spontaneous reports and differential dose-response effects were not evaluated. CONCLUSIONS: No evidence of clinically meaningful sex differences in the safety and tolerability of duloxetine were uncovered.

Adult↗
PubMed2006

Beyond remission: rationale and design of the Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study.

Recurrent major depressive disorder (MDD) is a common and disabling illness, but few studies have addressed long-term antidepressant treatment of recurrent MDD (ie, beyond 1 year of maintenance therapy) or compared the efficacy and safety of different antidepressant classes in this population. This article describes the rationale and design of a unique multi-phase trial in patients with recurrent MDD. The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study is a large double-blind, randomized, multi-center trial designed to assess the long-term efficacy of venlafaxine extended release (ER) in the prevention of depressive recurrence. Approximately 1,100 adult outpatients with MDD and a history of >or=3 lifetime episodes (with at least two occurring in the past 5 years) were randomized to 10 weeks of acute-phase treatment with either venlafaxine ER 75-300 mg/day or fluoxetine 20-60 mg/day, followed by 6 months of continuation-phase treatment for patients experiencing a satisfactory therapeutic response or remission during the acute phase. Responders and remitters to continuation phase treatment were then entered into a 2-year maintenance phase study, in which those receiving venlafaxine ER were re-randomized to either venlafaxine ER or placebo at the start of two 12-month maintenance periods. Those taking fluoxetine during the acute and continuation phases continued to receive double-blind treatment with fluoxetine. This study will address several unanswered questions about the long-term treatment of recurrent MDD, such as whether extended maintenance treatment (ie, up to 2 years) lessens the risk for developing future depressive episodes; whether fluoxetine and venlafaxine ER are effective for both short- and long-term treatment of MDD; whether rates of tachyphylaxis differ between antidepressant classes; and whether the likelihood of depressive recurrence differs according to the time point when treatment is discontinued.

Antidepressive Agents↗
PubMed2006

Duloxetine efficacy for major depressive disorder in male vs. female patients: data from 7 randomized, double-blind, placebo-controlled trials.

OBJECTIVE: A number of studies have suggested potential gender differences in the efficacy of antidepressant medications. Pooled data from double-blind, placebo-controlled studies were utilized to compare the efficacy of duloxetine in the treatment of major depressive disorder (MDD) in male and female patients. METHOD: Efficacy data were pooled from 7 randomized, double-blind, placebo-controlled clinical trials of duloxetine. These studies represent all available data from U.S. acute-phase, placebo-controlled studies of duloxetine for the treatment of MDD. Patients (aged > or = 18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day; men, N = 318; women, N = 578) or placebo (men, N = 242; women, N = 484) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score, HAM-D17 subscales (core, Maier, anxiety, retardation, sleep), the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Patient Global Impression of Improvement scale (PGI-I), the Quality of Life in Depression Scale (QLDS), and Visual Analog Scales (VAS) for pain. The first patient visit was February 1, 1999, and the last patient visit was November 27, 2002. RESULTS: In both male and female patients, duloxetine produced significantly greater improvement in HAM-D17, CGI-S, and PGI-I when compared with placebo (p < .05). Treatment-by-gender interactions did not reach statistical significance, indicating that the magnitude of duloxetine's treatment effects did not differ significantly between male and female patients. However, there was a trend for female patients to show a more robust response than male patients to both duloxetine and placebo. On the basis of VAS assessments of pain severity, duloxetine-treated female patients appeared to exhibit greater improvement than male patients, while women receiving placebo had smaller responses than placebo-treated men. Improvements in quality of life were significantly greater for both men (p = .006) and women (p = .001) receiving duloxetine than placebo and showed no significant difference by gender. CONCLUSION: In this analysis of pooled data, the efficacy of duloxetine did not differ significantly in male and female patients.

Adolescent↗
PubMed2006

Low-dose sertraline in the treatment of moderate-to-severe premenstrual syndrome: efficacy of 3 dosing strategies.

OBJECTIVE: Many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of premenstrual dysphoric disorder, but few studies have investigated the efficacy of SSRIs in the treatment of premenstrual syndrome (PMS). The objective of this study was to evaluate the safety and efficacy of sertraline in the treatment of moderate-to-severe PMS using 3 different dosing strategies: luteal phase (2 cycles), followed by continuous dosing throughout the month (1 cycle), followed by dosing begun at the first onset of PMS symptoms, or "symptom-onset" dosing (1 cycle). METHOD: 314 women with PMS from 22 U.S. sites were randomly assigned to fixed-dose treatment with sertraline (25 or 50 mg/day) or placebo for 4 menstrual cycles after a single-blind, placebo lead-in cycle. Assessments included the Daily Symptom Report (DSR), the Clinical Global Impressions-Severity of Illness and -Improvement scales, the Patient Global Evaluation scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, and the Social Adjustment Scale-Self Report. RESULTS: Intermittent luteal-phase dosing with low doses of sertraline (25 and 50 mg/day) produced significant improvement across 2 menstrual cycles, based on total DSR scores, compared with placebo. Continuous and symptom-onset dosing were also effective in treating PMS symptoms, particularly at the lower dose of 25 mg/day. CONCLUSIONS: The results of the current study suggest that low doses of sertraline may be a safe, effective, and well-tolerated treatment for moderate-to-severe PMS.

Adult↗
PubMed2006

Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial.

BACKGROUND: Major depressive disorder is a recurrent illness that often requires maintenance antidepressant treatment. Escitalopram is a selective serotonin reuptake inhibitor (SSRI) that has shown efficacy in both acute and continuation treatment of major depressive disorder. The current trial examined the efficacy of maintenance escitalopram treatment in preventing depression recurrence in patients who responded to acute SSRI therapy. METHOD: Patients with recurrent DSM-IV-defined major depressive disorder (>or= 2 previous episodes; baseline Montgomery-Asberg Depression Rating Scale [MADRS] score >or= 22) who had responded (MADRS score or= 22 or insufficient therapeutic response during the double-blind phase. The study was conducted between October 16, 2000, and February 4, 2003. RESULTS: A total of 234 patients who responded to acute open-label treatment with 1 of 4 SSRIs received at least 1 dose of open-label escitalopram continuation treatment. Of 164 patients who completed escitalopram continuation treatment, 139 were randomly assigned to double-blind maintenance treatment with escitalopram (N = 73) or placebo (N = 66). Mean baseline MADRS scores at the start of the maintenance phase were < 5 for both the placebo- and escitalopram-treatment groups. Time to recurrence was significantly longer in patients who received maintenance treatment with escitalopram compared with patients switched to placebo (hazard ratio = 0.26, 95% CI = 0.13 to 0.52, p < .001). Long-term escitalopram treatment was well tolerated. CONCLUSION: Maintenance treatment with escitalopram was well tolerated and significantly reduced the risk for recurrence of depression. Patients with few residual symptoms following continuation treatment with escitalopram experienced a high rate of depression recurrence when switched to placebo, demonstrating the need for maintenance therapy of recurrent major depressive disorder beyond 4 to 6 months of initial symptom resolution even if few residual symptoms are present.

Adult↗
PubMed2005

Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not.

CONTEXT: Although various strategies are available to manage nonresponders to an initial treatment for depression, no controlled trials address the utility of switching from an antidepressant medication to psychotherapy or vice versa. OBJECTIVE: To compare the responses of chronically depressed nonresponders to 12 weeks of treatment with either nefazodone or cognitive behavioral analysis system of psychotherapy (CBASP) who were crossed over to the alternate treatment (nefazodone, n = 79; CBASP, n = 61). DESIGN: Crossover trial. SETTING: Twelve academic outpatient psychiatric centers. PATIENTS: There were 140 outpatients with chronic major depressive disorder; 92 (65.7%) were female, 126 (90.0%) were white, and the mean age was 43.1 years. Thirty participants dropped out of the study prematurely, 22 in the nefazodone group and 8 in the CBASP group. INTERVENTIONS: Treatment lasted 12 weeks. The dosage of nefazodone was 100 to 600 mg/d; CBASP was provided twice weekly during weeks 1 through 4 and weekly thereafter. MAIN OUTCOME MEASURES: The 24-item Hamilton Rating Scale for Depression, administered by raters blinded to treatment, the Clinician Global Impressions-Severity scale, and the 30-item Inventory for Depressive Symptomatology-Self-Report. RESULTS: Analysis of the intent-to-treat sample revealed that both the switch from nefazodone to CBASP and the switch from from CBASP to nefazodone resulted in clinically and statistically significant improvements in symptoms. Neither the rates of response nor the rates of remission were significantly different when the groups of completers were compared. However, the switch to CBASP following nefazodone therapy was associated with significantly less attrition due to adverse events, which may explain the higher intent-to-treat response rate among those crossed over to CBASP (57% vs 42%). CONCLUSIONS: Among chronically depressed individuals, CBASP appears to be efficacious for nonresponders to nefazodone, and nefazodone appears to be effective for CBASP nonresponders. A switch from an antidepressant medication to psychotherapy or vice versa appears to be useful for nonresponders to the initial treatment.

Adult↗
PubMed2005

Self-reported depressive symptom measures: sensitivity to detecting change in a randomized, controlled trial of chronically depressed, nonpsychotic outpatients.

This study evaluated and compared the performance of three self-report measures: (1) 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR30); (2) 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16); and (3) Patient Global Impression-Improvement (PGI-I) in assessing clinical outcomes in depressed patients during a 12-week, acute phase, randomized, controlled trial comparing nefazodone, cognitive-behavioral analysis system of psychotherapy (CBASP), and the combination in the treatment of chronic depression. The IDS-SR30, QIDS-SR16, PGI-I, and the 24-item Hamilton Depression Rating Scale (HDRS24) ratings were collected at baseline and at weeks 1-4, 6, 8, 10, and 12. Response was defined a priori as a > or =50% reduction in baseline total score for the IDS-SR30 or for the QIDS-SR16 or as a PGI-I score of 1 or 2 at exit. Overall response rates (LOCF) to nefazodone were 41% (IDS-SR30), 45% (QIDS-SR16), 53% (PCI-I), and 47% (HDRS17). For CBASP, response rates were 41% (IDS-SR30), 45% (QIDS-SR16), 48% (PGI-I), and 46% (HDRS17). For the combination, response rates were 68% (IDS-SR30 and QIDS-SR16), 73% (PGI-I), and 76% (HDRS17). Similarly, remission rates were comparable for nefazodone (IDS-SR30=32%, QIDS-SR16=28%, PGI-I=22%, HDRS17=30%), for CBASP (IDS-SR30=32%, QIDS-SR16=30%, PGI-I=21%, HDRS17=32%), and for the combination (IDS-SR30=52%, QIDS-SR16=50%, PGI-I=25%, HDRS17=49%). Both the IDS-SR30 and QIDS-SR16 closely mirrored and confirmed findings based on the HDRS24. These findings raise the possibility that these two self-reports could provide cost- and time-efficient substitutes for clinician ratings in treatment trials of outpatients with nonpsychotic MDD without cognitive impairment. Global patient ratings such as the PGI-I, as opposed to specific item-based ratings, provide less valid findings.

Adolescent↗
PubMed2005

Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions.

OBJECTIVE: To investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender. METHODS: A pooled dataset from eight randomized, controlled trials of patients with major depressive disorder (MDD) was reanalyzed to compare remission rates following therapy with venlafaxine (n = 851), one of several selective serotonin reuptake inhibitors (SSRIs) (n = 748), or placebo (n = 446). Remission was defined as a final Hamilton Rating Scale for Depression (HAM-D) score < or =7. Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment, sex, and age (younger: <50; older: > or =50). Among older women, the impact of hormone replacement therapy (HRT) on remission rates also was examined. RESULTS: Remission rates on venlafaxine therapy were not affected by age, sex, or HRT use. Among women, but not men, there was a significant interaction reflecting poorer SSRI response in the older age group (Wald chi-square = 4.21, df = 1, p = 0.04); HRT appeared to eliminate this difference. Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women (6%-9%), the difference among older women not taking HRT was 23%. CONCLUSIONS: These findings provide further evidence that age, gender, and HRT moderate response to antidepressant medications.

Adult↗
PubMed2004

A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction.

OBJECTIVE: This study reports the results of a placebo-controlled, double-blind comparison of bupropion sustained release (SR) as an antidote for sexual dysfunction versus placebo in 42 patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. Exploratory analyses of the association of testosterone and sexual functioning in women in the study were also performed. METHOD: Patients with DSM-IV major depression who experienced a therapeutic response to any SSRI and were experiencing medication-induced global or phase-specific sexual dysfunction, as measured by the Changes in Sexual Functioning Questionnaire (CSFQ), were randomly assigned to receive either bupropion SR 150 mg b.i.d. or placebo for 4 weeks in addition to the SSRI. Total testosterone levels were assessed at baseline and week 4. RESULTS: The difference in global sexual functioning, based on the total CSFQ score, was not statistically significant between the 2 groups at week 4, nor were differences in orgasm, desire/ interest as measured by sexual thoughts, or self-reported arousal. There was a statistically significant difference between the 2 groups at week 4 in desire as measured by self-report feelings of desire and frequency of sexual activity. Desire/ frequency showed a significantly greater improvement among those patients receiving bupropion SR compared with placebo (Wilk's F = 5.47, df = 1, p =.024). Frequency was significantly correlated to total testosterone level at baseline (r = 0.36, p =.027) and at week 4 (r = 0.41, p =.025). CONCLUSIONS: Bupropion SR, as an effective antidote to SSRI-induced sexual dysfunction, produced an increase in desire to engage in sexual activity and frequency of engaging in sexual activity compared with placebo. A larger study is needed to further investigate this finding.

Administration, Oral↗
PubMed2003

Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression.

BACKGROUND: Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD. METHODS: A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians. RESULTS: Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p =.043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%). CONCLUSIONS: Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.

Acute Disease↗
PubMed2003

Gender differences in depression and response to antidepressant treatment.

Throughout their childbearing years, women are twice as likely as men to experience an episode of major depression. The exact etiology of this difference is unclear, but psychosocial and neurobiologic factors likely contribute. Clinicians should consider gender differences in the phenomenology of depression and response to antidepressant treatment when screening for depressive illness, selecting appropriate treatment and assessing therapeutic response. Treatment considerations when selecting an antidepressant should include the patient's gender, age, and, in women, menopausal status, including the use of concomitant HRT. Further research is needed to refine and extend the existing knowledge base regarding the effect of gender on treatment of depression, including the role of endogenous and exogenous gonadal hormones in response to antidepressant treatment.

Adult↗
PubMed2003

Chronic depression and comorbid personality disorders: response to sertraline versus imipramine.

BACKGROUND: Chronic subtypes of depression appear to be associated with high rates of Axis II personality disorder comorbidity. Few studies, though, have systematically examined the clinical correlates of Axis II personality disorder comorbidity or its effect on treatment response or time to response. METHOD: 635 patients diagnosed with DSM-III-R chronic major depression or "double depression" (dysthymia with concurrent major depression) were randomized to 12 weeks of double-blind treatment with either sertraline or imipramine between February 1993 and December 1994. Axis II diagnoses were made using the personality disorders version of the DSM-III-R Structured Clinical Interview. The effect of study treatment was measured utilizing the Hamilton Rating Scale for Depression and the Clinical Global Impressions scale. RESULTS: Forty-six percent of patients met criteria for at least 1 comorbid Axis II personality disorder, with cluster C diagnoses being the most frequent at 39%; 21% met criteria for at least 2 Axis II personality disorders. A cluster C diagnosis was associated with significantly higher rates of early-onset depression (before age 21; 47% vs. 32% for no cluster C; p =.005) and comorbid anxiety disorder (34% vs. 18% for no cluster C; p <.001). Overall, the presence of Axis II personality disorder comorbidity had minimal-to-no effect on the ability to achieve either an antidepressant response or remission and had inconsistent effects on time to response. The presence of Axis II personality disorder comorbidity did not appear to reduce functional and quality-of-life improvements among patients responding to acute treatment with sertraline or imipramine. CONCLUSION: In this treatment sample, rates of Axis II personality disorder comorbidity were substantial in patients suffering from chronic forms of depression. Axis II personality disorder comorbidity did not appear to diminish symptomatic response to acute treatment or associated improvement in functioning and quality of life.

Adult↗
PubMed2003

Continuation treatment of chronic depression: a comparison of nefazodone, cognitive behavioral analysis system of psychotherapy, and their combination.

Little is known about the relative benefits of psychotherapy, medication, and combined treatment as continuation therapies for chronic forms of major depressive disorder (MDD) after a positive response to acute treatment. We hypothesize that combined treatment would demonstrate superior continuation phase outcomes compared to either monotherapy, as evidenced by lower relapse rates and greater rates of improvement from partial to full remission. We report 16-week continuation phase outcomes for 324 patients who had participated in either the acute phase of a randomized multicenter trial of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combination therapy (COMB) for chronic forms of MDD. Patients entering the continuation phase had either fully or partially remitted after 12 weeks of acute phase treatment. The primary efficacy measure was the 24-item Hamilton Rating Scale for Depression. For patients in remission at acute phase exit, 73.3% (107/146) maintained their remitted status at endpoint of the continuation phase. Of those having a partial remission at acute phase exit, 52.9% (92/174) achieved full remission by end of continuation. A greater proportion of patients maintained a partial or full remission status on COMB (90%) compared to nefazodone (80%, p=0.011) or to CBASP (82%, p=0.042). These differences reflected greater symptom re-emergence in the partial remission groups on CBASP and nefazodone monotherapy compared to COMB. Continuation treatment assignment was not randomized or blinded. There was no placebo group. Most patients with chronic forms of MDD sustained their acute phase response and more than 50% of partial remitters achieved full remission while continuing treatment with nefazodone, CBASP, or COMB. COMB was associated with less symptom re-emergence during the continuation phase than either monotherapy, particularly for partial remitters.

Adolescent↗
PubMed2002

Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination.

BACKGROUND: Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients. METHODS: Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial assessments measured overall psychosocial functioning, work functioning, interpersonal functioning, and general health. RESULTS: Relative to community norms, patients with chronic major depression evidenced substantially impaired psychosocial functioning at baseline. Combined treatment produced significantly greater psychosocial improvement than either CBASP alone or nefazodone alone on all primary measures. Combined treatment remained superior to nefazodone on primary measures of work, social, and overall functioning, and superior to CBASP on social functioning when depressive symptoms were controlled. Unlike the two groups receiving nefazodone, CBASP alone's effect on psychosocial function was relatively independent of symptom change. Psychosocial functioning improved more slowly than depressive symptoms, and moderate psychosocial impairments remained at end point. CONCLUSIONS: Combined treatment had greater effect than either monotherapy. Change in depressive symptoms did not fully explain psychosocial improvement. Moderate residual psychosocial impairment remained, suggesting the need for continuation/maintenance treatment.

Adult↗
PubMed2002

Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression.

BACKGROUND: Although various strategies have been proposed to treat antidepressant nonresponders, little controlled research has been published that examines prospectively the use of switching to an alternate antidepressant. METHODS: This was a multisite study in which outpatients with chronic major depression (with or without concurrent dysthymia), who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication. Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions--Severity and Improvement scales. RESULTS: The switch from sertraline to imipramine (mean dosage, 221 mg/d) and from imipramine to sertraline (mean dosage, 163 mg/d) resulted in clinically and statistically significant improvements. The switch to sertraline treatment was associated with fewer adverse effect complaints and significantly less attrition owing to adverse effects. Although sertraline treatment also resulted in significantly higher response rates in the intent-to-treat samples (60% in the sertraline group and 44% in the imipramine group), neither the intent-to-treat remission rates nor the response and remission rates among study completers differed significantly. Moreover, after considering the effect of attrition, there were no significant treatment effects on the more comprehensive generalized estimating equation analyses of the continuous dependent measures. CONCLUSIONS: More than 50% of chronically depressed antidepressant nonresponders benefited from a switch from imipramine to sertraline, or vice versa, despite a high degree of chronicity. As in the initial trial, sertraline was generally better tolerated than imipramine. Switching to a standard antidepressant of a different class is a useful treatment strategy for antidepressant nonresponders and could be considered a standard of comparison for future studies of novel alternate strategies.

Adult↗
PubMed2002

Symptomatic and syndromal anxiety in chronic forms of major depression: effect of nefazodone, cognitive behavioral analysis system of psychotherapy, and their combination.

BACKGROUND: Limited information is available on treatment response of anxiety symptoms in chronic forms of major depression. Concurrent anxiety disorders are prevalent in chronic depression, but the responsiveness of patients with such comorbidity to different treatments is largely unknown. This study investigated the comparative efficacy of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), and their combination in improving anxiety symptoms in patients with chronic forms of major depression, including those with a concurrent anxiety disorder. METHOD: 681 patients with chronic major depressive disorder (DSM-IV criteria) participated in a multicenter study of 12 weeks of acute treatment with nefazodone (N = 226), CBASP (N = 228), or the combination (N = 227). The Hamilton Rating Scale for Anxiety (HAM-A), the HAM-A psychic anxiety factor, and the anxiety/arousal subscale of the 30-item Inventory for Depressive Symptomatology-Self Report (IDS-SR-30) were used to assess anxiety symptoms. RESULTS: In the full sample. without controlling for change in depressive symptoms, combination therapy was superior to both monotherapies on all 3 anxiety measures both in the rate of change and at endpoint. When change in depressive symptoms was controlled for, there were no treatment differences in rate of change from baseline to week 12 on any of the 3 anxiety measures. In those patients with a concurrent anxiety disorder, however, the combination was superior to CBASP on the HAM-A and the IDS-SR-30. Nefazodone alone and combination therapy were both superior to CBASP on the HAM-A psychic anxiety factor. CONCLUSION: For patients with chronic depression, combination therapy is superior to CBASP or nefazodone alone. Among patients with a concurrent anxiety disorder, nefazodone. either alone or in combination with CBASP, improves anxiety symptoms faster than CBASP alone, independent of depressive symptom reduction.

Adult↗
PubMed2002

Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression.

BACKGROUND: The antidepressant nefazodone and the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) were recently found to have significant, additive effects in a large multicenter study of chronic forms of major depression. As nefazodone-mediated blockade of serotonin-2 receptors may directly relieve insomnia associated with depression, we examined the more specific effects of CBASP and nefazodone, singly and in combination, on sleep disturbances. METHOD: A total of 597 chronically depressed outpatients (DSM-III-R criteria) with at least 1 insomnia symptom were randomly assigned to 12 weeks of treatment with nefazodone (mean final dose = 466 mg/day), CBASP (mean = 16.0 sessions), or the combination (mean dose = 460 mg/day plus a mean of 16.2 CBASP sessions). Continuous and categorical insomnia outcomes, derived from standard clinician- and self-rated assessments, were compared. RESULTS: Patients receiving nefazodone (either alone or in combination with CBASP) obtained significantly more rapid and greater ultimate improvement in insomnia ratings when compared with those treated with CBASP alone. This difference was maximal by the fourth week of therapy and sustained thereafter. Combined treatment did not result in markedly better insomnia scores than treatment with nefazodone alone on most measures, although patients receiving both CBASP and nefazodone were significantly more likely (p < .001) to achieve > or = 50% decrease in insomnia severity. CONCLUSION: Despite comparable antidepressant efficacy, monotherapy with nefazodone or CBASP resulted in markedly different effects on the magnitude and temporal course of insomnia symptoms associated with chronic forms of major depression. Patients receiving the combination of psychotherapy and pharmacotherapy benefited from both the larger and more rapid improvements in insomnia associated with nefazodone therapy and the later-emerging effects of CBASP on the overall depressive syndrome.

Adult↗