Increased premenstrual dosing of nefazodone relieves premenstrual magnification of depression

We report on 3 subjects with premenstrual magnification of major depression (PMMD) treated with nefazodone who benefited from a supplement of additional nefazodone premenstrually. During the 6-month study, subjects were given supplements of either additional nefazodone or placebo prior to the expected onset of menses (double-blind crossover design). Symptoms were assessed during the late luteal and follicular phases. All subjects showed significant improvement for the months in which they received nefazodone supplements, but not when given placebo. Premenstrual dose increase is a clinically promising intervention for women who experience PMMD.     

The efficacy of nefazodone augmentation for treatment-resistant depression with anxiety symptoms or anxiety disorder

Depression that fails to respond to multiple antidepressant trials, particularly when accompanied by anxiety, constitutes a difficult treatment challenge. Those with anxious depression may be less likely to respond to treatment than their cohorts without anxiety. Anxiety symptoms also predict a higher rate of suicide, particularly if the symptoms do not improve early in the course of treatment. Eleven consenting outpatients with treatment-resistant depression and/or comorbid anxiety disorders were treated with nefazodone, slowly added to their ongoing treatment regimens. Doses were initiated at 50 mg a day and slowly increased by 50 mg increments until an optimum response was achieved. The Clinical Global Impression of Improvement (CGI) Scale was employed to monitor the medication effects. In all 11 cases, nefazodone was efficacious and well tolerated in the treatment of both depressive and anxiety components. After nefazodone augmentation, the mean CGI score for combined depression and anxiety symptoms was (+/-sd) 1.52 (0.52) on a scale from 1 (very much better) to 7 (very much worse). Seven of the 11 cases achieved complete remission of depressive symptoms (chi(2)=11.55, P<.005) and 9 of the 11 cases, complete remission of anxiety symptoms (chi(2)=15.23, P<.0005). The mean effective dose for nefazodone (mean+/-sd) was 200.0 (34.2) mg a day (range 50-300 mg a day). Nefazodone's unique pharmacologic profile may explain its unusual efficacy in these cases of treatment-resistant major depression.     

An open-label study of nefazodone treatment of major depression in patients with congestive heart failure.

OBJECTIVES: To evaluate the feasibility of screening and recruiting patients with major depression and congestive heart failure (CHF) in a tertiary care cardiology hospital and to obtain preliminary efficacy, tolerability, and safety data for nefazodone treatment of a major depressive episode in CHF patients. METHOD: We conducted a 12-week, open-label trial of nefazodone given in dosages up to 600 mg daily. We assessed patients at baseline, 1, 2, 4, 8, and 12 weeks. Measures used were the 17-item Hamilton Depression Rating Scale (HDRS), the Clinical Global Impression Scale, the Beck Depression Inventory, Spielberger's State-Trait Anxiety Inventory, and the Minnesota Living with Heart Failure Questionnaire. We also obtained pre- and poststudy ECGs, 24-hour Holter monitor recordings, and plasma levels of norepinephrine. RESULTS: After screening 443 CHF patients, 28 patients with major depression met study eligibility criteria. The 23 patients who completed 4 or more weeks of medication showed significant improvement on all depression scales and in quality of life. Of 19 subjects who completed the full 12-week trial, 74% experienced a decline of 50% or more on HDRS scores. The completers also showed a significant reduction in heart rate, an increase in QT intervals (but not in the QTc), and a marginally significant decrease in plasma norepinephrine. There were no changes in heart rate variability. CONCLUSIONS: It is feasible to screen and recruit CHF patients with major depression for an anti-depressant trial. Nefazodone seems sufficiently safe, tolerable, and efficacious to justify a larger, placebo-controlled trial.     

Discontinuation symptoms with nefazodone.

OBJECTIVE: We report a patient who developed discontinuation symptoms following nefazodone cessation. CLINICAL PICTURE: The patient experienced nausea, vomiting, diarrhoea, ataxia, insomnia, marked agitation, headache and flu-like symptoms. TREATMENT: She was reluctant to recommence nefazodone and was symptomatically treated with oxazepam. OUTCOME: The patient recovered completely in 10 days. CONCLUSIONS: Nefazodone discontinuation can result in withdrawal symptoms and therefore needs to be tapered gradually. Those who have experienced discontinuation symptoms with other antidepressants in the past may be at increased risk.     

Cost savings associated with fitness-to-stand-trial assessments in detention centres: a pilot program.

OBJECTIVE: To determine whether fitness-to-stand-trial assessments "in detention" offer cost benefit over inpatient assessments. METHOD: The development of a pilot "fitness clinic" in a detention centre is described, and the results of 1 year of assessments are presented. The cost benefit of fitness assessments conducted in detention centres is outlined. RESULTS: Significant cost savings were realized by operating fitness clinics in detention centres. CONCLUSION: Fitness clinics in detention centres offer important benefits and are recommended as an adjunct to forensic programs.     

Methylphenidate in treating poststroke depression

The authors retrospectively studied the charts of 25 patients with poststroke depression who were treated with methylphenidate. The 13 patients (52%) who recovered completely from their depression did not differ significantly from the 12 nonresponders on demographic characteristics, location of cerebrovascular accident, and other variables. Mood usually improved within 48 hours; only 3 (12%) patients had side effects. Rapid response to treatment and lack of significant side effects indicate that methylphenidate may be a valuable treatment for poststroke depression.     

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.     

Open trial of nefazodone among Hispanics with major depression: efficacy, tolerability, and adherence issues

The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score > or = 18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with > or = 1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58-69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD = 170), also within the range of previous trials (321-472 mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by > 6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21-33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports.     

帕罗西汀和氟西汀治疗伴焦虑症状抑郁症的疗效对照分析

目的　比较帕罗西汀和氟西汀治疗伴焦虑症状的抑郁症的临床疗效及副反应。方法　符合CCMD - 3抑郁症的诊断标准 ,并且汉密尔顿焦虑量表评分 >14分的门诊及住院患者 5 8例 ,随机分为两组 ,为期 6周的治疗 ,于治疗前及治疗后第 1、2、4、6周末用汉密尔顿抑郁量表 (HAMD)、汉密尔顿焦虑量表 (HAMA)评定疗效 ,以不良反应症状量表 (TESS)观察副作用。结果　帕罗西汀和氟西汀治疗伴焦虑症状的抑郁症的显效率分别为 85 19%和 81 4 8% ,无显著差异。两组的HAMD减分率亦相当 (P >0 0 5 )。两组的HAMA减分率有显著差异 (P <0 0 5 )。两组的副反应相当 ,且均较轻。结论　帕罗西汀和氟西汀对伴焦虑症状的抑郁症的疗效均显著 ,抗抑郁效果两药相当 ,抗焦虑效果前者优于后者。两者副反应均较轻。     

An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [18F]-setoperone for 5-HT2 binding potential (BP) and [11C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [18F]-setoperone and with [11C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as >or=50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.     

An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [¹⁸F]-setoperone for 5-HT2 binding potential (BP) and [¹¹C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [¹⁸F]-setoperone and with [¹¹C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.     

Cost of depression: prospective analysis. Follow-up study in patients with recurrent depression

This article presents a comparison of costs of the first, the second, the third or next episode of depression, based on preliminary results of an observation clinical trial.     

Sexual function and satisfaction in the treatment of chronic major depression with nefazodone,psychotherapy, and their combination

BACKGROUND: Changes in sexual interest/satisfaction and function are frequently associated with major depression and the use of some antidepressant treatments. This study compares the effects of antidepressant medication, psychotherapy, and combined treatment on sexual interest/satisfaction and function in patients with chronic major depression. METHOD: Outpatients with chronic forms of DSM-IV major depressive disorder (N = 681) were randomly assigned to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. The Modified Rush Sexual Inventory was used to assess sexual functioning, and the 24-item Hamilton Rating Scale for Depression was used to assess depressive symptoms. RESULTS: At baseline, 65% of men and 48% of women reported some sexual dysfunction. Statistically significant linear improvement in sexual interest/satisfaction was noted across all 3 treatment groups (p < .001). Additionally, significant improvement in sexual function was observed across all 3 treatment groups on a composite measure of female sexual function (p < .001). Controlling for depressive symptoms and gender, combined treatment produced greater improvement in total sexual interest/satisfaction than CBASP alone (p = .007), but was not significantly different from nefazodone alone. Improvement in depressive symptoms was associated with improved sexual interest/satisfaction for men and women and, for men, improved sexual functioning. CONCLUSION: Chronic depression is associated with high rates of sexual dysfunction. Treatment with nefazodone, CBASP, and combined treatment improved sexual interest/satisfaction, with greatest improvement observed with combined treatment.     

Hepatic adverse reactions associated with nefazodone.

OBJECTIVE: Since 1999, international reports of hepatotoxicity associated with the antidepressant nefazodone (Serzone) have increased. In June 2001, a manufacturer's safety advisory notified Canadian physicians of "very rare reports of severe liver injury temporally associated with the use of nefazodone HC1." We undertook this study to determine the prevalence of adverse drug reactions to nefazodone reported in a Canadian database. METHOD: We requested the Canadian Adverse Drug Reaction Monitoring Programme (CADRMP) database for nefazodone and analyzed it for suspected hepatic complications reported and entered from the time of marketing to June 30, 2001. RESULTS: We found 32 cases of liver injury associated with nefazodone, with 26 (81.3%) classified as "severe." Patients ranged in age from 30 to 69 years and took 100 to 600 mg of nefazodone daily. Most (68.8%) of the patients were women. Eleven patients were prescribed only nefazodone, and 20 took it concomitantly with other drugs. Of affected patients, 88% developed liver injury within 6 months of starting nefazodone. At the time of reporting, 17 patients recovered without sequelae, 12 patients had not yet recovered, and the outcomes for 3 were unknown. There were 3 cases of hepatic failure, 1 of hepatocellular degeneration, 1 of hepatic necrosis, and 1 of fulminant hepatitis. CONCLUSION: In common with similar databases, the CADRMP database includes only a small proportion of suspected drug reactions. In view of 32 reported cases of hepatotoxicity associated with nefazodone in Canada, 81.3% of which were severe, caution should be exercised if nefazodone is prescribed with other drugs, especially those metabolized by CYP4503A4. Nefazodone should not be prescribed to patients with preexisting liver disease. Baseline and regular liver function tests should be obtained in all patients on nefazodone therapy in the first 6 months, and the drug should be discontinued if abnormalities are found. Patients should be advised of symptoms of hepatotoxicity, and to report them immediately to their physician.