Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine.

BACKGROUND: Limited information is available regarding optimal dosing or long-term pharmacotherapy with serotonin reuptake inhibitors in obsessive-compulsive disorder. This study evaluated the acute safety and efficacy and long-term efficacy, safety, and impact on relapse prevention of paroxetine in obsessive-compulsive disorder. METHOD: We enrolled 348 outpatients with DSM-III-R obsessive-compulsive disorder in phase 1, a 12-week randomized, double-blind, parallel study of fixed doses of paroxetine (20 mg/day, 40 mg/day, or 60 mg/day) and placebo. In phase 2, 263 phase 1 completers were enrolled in 6 months of flexibly dosed open-label paroxetine treatment. In phase 3, 105 responders to open-label paroxetine were randomized to 6-month double-blind, fixed-dose, parallel paroxetine/placebo treatment to evaluate long-term efficacy, safety, and impact on relapse prevention. The study was conducted from July 1991 to February 1994. RESULTS: Patients in phase 1 acute treatment receiving 40 mg/day or 60 mg/day of paroxetine improved significantly (p < .05) more than those receiving placebo; the mean reduction in Yale-Brown Obsessive-Compulsive Scale score was 25% on 40 mg/day of paroxetine and 29% on 60 mg/day compared with 13% on placebo. During phase 3, long-term treatment, a greater proportion of placebo- (59%) than paroxetine-treated (38%) patients relapsed. Paroxetine was well tolerated at all doses, with no significant increase in frequency of adverse events during long-term compared with short-term therapy. Greater adverse events in the placebo than in the paroxetine group in phase 3 probably represent a discontinuation effect. CONCLUSION: Paroxetine doses of 40 mg/day and 60 mg/day (but not 20 mg/day) are effective in treating acute obsessive-compulsive disorder. Long-term treatment with paroxetine is effective and safe, decreases the rate of relapse, and lengthens the time to relapse.

A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of generalized social anxiety disorder.

BACKGROUND: This multicenter, double-blind, placebo-controlled study was carried out to determine the effectiveness and safety of various daily dosages of paroxetine for the treatment of generalized social anxiety disorder. METHOD: A 1-week, single-blind, placebo run-in was followed by 12 weeks of double-blind treatment. 384 eligible patients meeting DSM-IV criteria for social anxiety disorder were randomly assigned to receive paroxetine, 20 (N = 97), 40 (N = 95), or 60 mg (N = 97), or placebo (N = 95) once daily in a 1:1:1:1 ratio. Primary efficacy variables included mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and proportion of patients exhibiting a therapeutic response (defined as a Clinical Global Impressions-Global Improvement scale [CGI-1] score of 1 or 2). RESULTS: In the last-observation-carried-forward analyses, patients treated with paroxetine, 20 mg/day, had significantly greater improvement on mean LSAS total scores compared with those receiving placebo (p < .001), while the incidence of responders, based on the CGI-I rating, was significantly greater with paroxetine, 40 mg/day, than with placebo (p = .012). Patients treated with paroxetine, 20 and 60 mg, also had significantly better responses on the social item of the Sheehan Disability Scale than did patients treated with placebo (p < .019). The completer analyses showed a significant difference between the placebo group and the 20-mg and 40-mg paroxetine groups on LSAS total score and rate of response (p < or = .006). There were no serious adverse experiences attributed to paroxetine treatment. CONCLUSION: Paroxetine, 20 mg/day, is an effective and safe treatment for patients with generalized social anxiety disorder and significantly improves social anxiety, avoidance of social interactions, social disability, and overall clinical condition. Further data analyses are needed to determine whether more specific guidelines for paroxetine dosage escalation in social anxiety disorder can be drawn.

Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.

CONTEXT: Beta-blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some beta-blockers. OBJECTIVE: To compare the effects of beta-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. INTERVENTIONS: Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. MAIN OUTCOME MEASURES: Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. RESULTS: The 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], -0.22% to -0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48); the between-group difference was -7.2% (95% CI, -13.8% to -0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). CONCLUSIONS: Both beta-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 beta-blockers on clinical outcomes need to be compared in long-term clinical trials.