Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials.

OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of extended-release venlafaxine in the treatment of pediatric generalized anxiety disorder. METHOD: Two randomized, double-blind, placebo-controlled trials were conducted at 59 sites in 2000 and 2001. Participants 6 to 17 years of age who met DSM-IV criteria for generalized anxiety disorder received a flexible dosage of extended-release venlafaxine (N=157) or placebo (N=163) for 8 weeks. The primary outcome measure was the composite score for nine delineated items from the generalized anxiety disorder section of a modified version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and the primary efficacy variable was the baseline-to-endpoint change in this composite score. Secondary outcome measures were overall score on the nine delineated items, Pediatric Anxiety Rating Scale, Hamilton Anxiety Rating Scale, Screen for Child Anxiety Related Emotional Disorders, and the severity of illness and improvement scores from the Clinical Global Impression scale (CGI). RESULTS: The extended-release venlafaxine group showed statistically significant improvements in the primary and secondary outcome measures in study 1 and significant improvements in some secondary outcome measures but not the primary outcome measure in study 2. In a pooled analysis, the extended-release venlafaxine group showed a significantly greater mean decrease in the primary outcome measure compared with the placebo group (-17.4 versus -12.7). The response rate as indicated by a CGI improvement score <3 was significantly greater with extended-release venlafaxine than placebo (69% versus 48%). Common adverse events were asthenia, anorexia, pain, and somnolence. Statistically significant changes in height, weight, blood pressure, pulse, and cholesterol levels were observed in the extended-release venlafaxine group. CONCLUSIONS: Extended-release venlafaxine may be an effective, well-tolerated short-term treatment for pediatric generalized anxiety disorder.

Venlafaxine ER for the treatment of pediatric subjects with depression: results of two placebo-controlled trials.

OBJECTIVE: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. METHOD: Participants received venlafaxine ER (flexible dose, based on body weight; intent to treat, n = 169) or placebo (intent to treat, n = 165) for up to 8 weeks. The primary efficacy variable was the change from baseline in the Children's Depression Rating Scale-Revised score at week 8. RESULTS: There were no statistically significant differences between venlafaxine ER and placebo on the Children's Depression Rating Scale-Revised in either study. A post hoc age subgroup analysis of the pooled data showed greater improvement on the Children's Depression Rating Scale-Revised with venlafaxine ER than with placebo (-24.4 versus -19.9; p = .022) among adolescents (ages 12-17), but not among children (ages 7-11). The most common adverse events were anorexia and abdominal pain. Hostility and suicide-related events were more common in venlafaxine ER-treated participants than in placebo-treated participants. There were no completed suicides. CONCLUSIONS: Venlafaxine ER may be effective in depressed adolescents. However, its safety and efficacy in pediatric patients has not been established. Prescribers should monitor for signs of suicidal ideation and hostility in pediatric patients taking venlafaxine ER.

Long-term, open-label venlafaxine extended-release treatment in children and adolescents with major depressive disorder.

INTRODUCTION: Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited. OBJECTIVE: To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD. METHODS: Subjects (n=86) 7-17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population). RESULTS: Mean CDRS-R total score decreased from 60.1+/-10.0 at baseline to 36.3+/-13.1 at week 6, and to 33.8+/-15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3+/-7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides. CONCLUSION: Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.

Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study.

To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150-225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness and the Clinical Global Impressions-Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; P < 0.001 vs placebo). Mean VAS-PR scores in the 150-225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm; P < 0.001). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150-225 mg was 4.5 at week 6. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment. Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy. NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin.

Venlafaxine versus placebo in the preventive treatment of recurrent major depression.

BACKGROUND: Major depression is often chronic and recurrent, yet most long-term therapeutic trials are not adequately designed to assess antidepressant efficacy in recurrence prevention. Long-term efficacy and safety of prophylactic venlafaxine treatment were evaluated in outpatients with recurrent major depression. METHOD: Patients with a history of recurrent DSM-III-R major depression received open-label treatment with venlafaxine, 100 to 200 mg/day, for 6 months. Those who responded to treatment (Hamilton Rating Scale for Depression [HAM-D(21)] score < or = 12, day 56) and remained relapse-free (no more than 2 HAM-D(21) scores > 10 and no Clinical Global Impressions-Severity of Illness [CGI-S] score > or = 4, months 2-6) either continued taking venlafaxine, 100 to 200 mg/day, or were switched in a double-blind fashion to placebo for 12 months. The primary efficacy outcome was the number of patients experiencing a recurrence of major depression (CGI-S score > or = 4). The cumulative probability of recurrence was calculated using the Kaplan-Meier method of survival analysis. Data were collected from November 1992 through December 1995. RESULTS: Of the 235 patients who enrolled in the recurrence-prevention period, 225 (N = 109, venlafaxine; N = 116, placebo) provided efficacy data. Survival analysis determined a 22% cumulative probability of recurrence in venlafaxine-treated patients after 12 months compared with 55% for the placebo group (p <.001). More than twice as many placebo-treated patients (48%) as venlafaxine-treated patients (21%) discontinued treatment because of lack of efficacy (p <.001). CONCLUSION: Twelve-month maintenance venlafaxine treatment was significantly more efficacious than placebo in preventing major depression recurrence in patients who had been successfully treated with venlafaxine for 6 months.

Extended-release venlafaxine in relapse prevention for patients with major depressive disorder.

Many studies have demonstrated that venlafaxine is an efficacious and safe treatment for major depressive disorder (MDD). This double-blind, placebo-controlled study was performed to evaluate the efficacy of venlafaxine extended-release (XR) (75-225 mg/day) in the prevention of relapse of depression. Patients with MDD who responded to an 8-week course of venlafaxine XR treatment, i.e., had a score < or = 3 on the Clinical Global Impressions scale-Severity of Illness item (CGI-S) and a 21-item Hamilton Rating Scale for Depression (HAM-D(21)) score < or = 10, were randomly assigned to receive continuation treatment (up to 6 months) with venlafaxine XR (n=161) or placebo (n=157). The main efficacy outcome measure was the number of patients who experienced a relapse of depression. Relapse was defined by either a combination of a patient meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for MDD and a CGI-S score > or = 4, two consecutive CGI-S scores > or = 4, or a final CGI-S score > or = 4 for a patient who withdrew from the study. The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis. During the 6-month evaluation period, significantly more patients in the placebo group had a relapse of MDD than did patients who continued treatment with venlafaxine XR. Cumulative relapse rates at 3 and 6 months were 19 and 28%, respectively, for venlafaxine XR, and 44 and 52%, respectively, for placebo. This study demonstrates that venlafaxine XR is an effective and safe continuation therapy.