Low doses of controlled-release paroxetine in the treatment of late-life depression: a randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of low daily doses of controlled-release (CR) paroxetine in patients with late-life depression. METHOD: This was a 10-week, multicenter, placebo-controlled, double-blind, fixed-dose trial randomly assigning patients >or= 60 years old to daily doses of paroxetine CR 12.5 mg (N = 168), paroxetine CR 25 mg (N = 177), or placebo (N = 180). Patients had major depressive disorder (DSM-IV criteria) and 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of >or= 18. The primary efficacy variable was the change from baseline to study endpoint in total HAM-D scores. The study was conducted from June 2003 to October 2004. RESULTS: The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 (95% CI = -3.41 to -0.19, p = .029) for paroxetine CR 12.5 mg, and -3.3 (95% CI = -4.84 to -1.68, p < .001) for paroxetine CR 25 mg. A significantly larger percentage of patients achieved remission (HAM-D total score or= 60 years of age, although effect sizes are relatively smaller with the 12.5 mg/day dose.

Paroxetine response and tolerability among ethnic minority patients with mood or anxiety disorders: a pooled analysis.

BACKGROUND: Because of the poor quality of mental health care received by minorities, analyses documenting comparable response to and tolerability of medications for anxiety and depression in large samples of minority and majority populations could increase the willingness of providers and patients to use medications in minority populations. METHOD: A pooled analysis of 14,875 adults who participated in 104 double-blind, placebo-controlled paroxetine clinical trials investigating major depression, panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, or premenstrual dysphoric disorder from March 1984 through March 2002. An intent-to-treat analysis with last observation carried forward used the Clinical Global Impressions (CGI) scale to measure dichotomous outcome, classified as either response (CGI score of 1 or 2) or more complete response (CGI score of 1) ("full response"). Minority group differences were examined using logistic regression for the entire sample and repeated for those with major depression. Adverse events greater than 5% and twice the rate of placebo were descriptively tabulated. Finally, a survival analysis examined group differences in speed of onset of response. RESULTS: Hispanic and Asian subjects had a slightly lower response rate, while Asians had the highest rates and Hispanics had the lowest rates of "full response." The more consistent Hispanic outcome differences appeared to be due to a higher placebo response rate. There was no treatment by minority group interaction for depressed patients. Speed of response and adverse effects were similar across groups. CONCLUSIONS: There were few consistent differences in medication response and tolerability. These findings may serve to counteract the greater rate of negative attitudes toward medication use among minorities and reinforce the value of medications used to treat anxiety and depression in minorities.

Efficacy and tolerability of controlled-release paroxetine in the treatment of severe depression: post hoc analysis of pooled data from a subset of subjects in four double-blind clinical trials.

OBJECTIVES: The aims of this work were to assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of outpatients with severe major depressive disorder (MDD). METHODS: This was a retrospective analysis of pooled data from 4 previously published, double-blind, randomized, placebo-controlled, 8- to 12-week outpatient studies of paroxetine CR (12.5-62.5 mg) in MDD. However, the studies were designed to assess the efficacy of paroxetine CR overall, rather than specifically in those with severe MDD. Subjects were categorized according to their baseline mean 17-item Hamilton Depression Rating Scale (HAMD-17) total score as having severe (> or =25) or nonsevere (<25) depression. Changes in depressive symptomatology were assessed, based on the mean change from baseline in HAMD-17 total scores and the proportion of responders (> or =50% reduction from baseline in HAMD-17 total scores or Clinical Global Impression [CGI] of Improvement scores of 1 or 2), for each study and pooled across the studies. The pooled analysis of data also assessed the proportion of patients achieving remission (HAMD-17 total score < or =7 or CGI-Improvement score of 1) at last-observation-carried-forward end point. RESULTS: A total of 1083 subjects participated in the 4 studies; 303 had severe MDD (paroxetine CR, n = 174; placebo, n = 129). Among the patients with severe MDD, most were women, had a mean HAMD-17 score between 26.3 and 27.7, and had a mean CGI of Severity score between 4.5 and 4.9. In 3 studies, the mean age of such participants was between 35 and 43 years. However, the fourth study was an evaluation in late-life depression in which the mean age was 71.3 years in the paroxetine CR group and 70.0 years in the placebo group. In the overall pooled sample, significantly greater improvements in depressive symptoms were observed among those with severe MDD who were treated with paroxetine CR compared with those who received placebo (HAMD-17 total treatment difference, -4.37 [95% CI, -6.31 to -2.42; P < 0.001]). The odds of CGI-Improvement response were also significantly higher for patients receiving paroxetine CR than those receiving placebo, regardless of baseline depressive symptomatology (severe MDD: odds ratio [OR], 2.42 [95% CI, 1.50-3.91; P < 0.001]; nonsevere MDD: OR, 1.63 [95% CI, 1.21-2.19; P < 0.002] ). Withdrawal rates due to adverse events were 9.8% versus 5.4% (severe) and 5.2% versus 4.5% (nonsevere), paroxetine CR versus placebo, respectively. CONCLUSIONS: This post hoc analysis of pooled data suggests that paroxetine CR was effective and well tolerated in these outpatients with severe MDD.

Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder.

CONTEXT: Paroxetine controlled release (CR) is approved for the treatment of major depressive disorder (MDD) in the dosage range of 25 to 62.5 mg daily. However, lower daily doses (12.5 mg and 25 mg) of this formulation have not been investigated in the treatment of MDD. If the 12.5-mg and 25-mg doses are found to be efficacious, these lower doses may well convey a superior tolerability profile for paroxetine CR in the treatment of MDD. OBJECTIVE: To evaluate the antidepressant efficacy and tolerability profile of daily doses of paroxetine CR 12.5 mg and 25 mg versus placebo in the treatment of MDD. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted in 40 clinical investigation centers in the United States. PARTICIPANTS: 447 adult (> or = 18 years of age) outpatients who met DSM-IV criteria for MDD and with a baseline 17-item Hamilton Rating Scale for Depression (HAM-D) score of at least 20 comprised the intent-to-treat study population (mean age = 38.8 years; 58.4% female; 75.6% white). INTERVENTION: Eligible patients completing a 1-week single-blind placebo run-in period were randomly assigned to receive once-a-day study medication (paroxetine CR 12.5 mg [N = 156], paroxetine CR 25 mg [N = 154], or placebo [N = 149]) in an 8-week, double-blind, parallel cell comparison. MAIN OUTCOME MEASURES: The primary efficacy measure was the change from baseline to study endpoint (week 8) as measured by the HAM-D. Secondary efficacy measures included change from baseline to study endpoint as assessed by both the depressed mood item on the HAM-D and the Clinical Global Impressions (CGI) Severity of Illness scale (CGI-S). The proportion of patients considered at study endpoint to be in response (CGI-Improvement score of 1 or 2) or in remission (HAM-D < or = 7) in the 3 treatment groups was also compared. Quality of life was assessed by the change from baseline in total score of the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Safety observations were made by assessing the proportion of patients who had adverse experiences, including laboratory and electrocardiographic abnormalities, during the treatment period. RESULTS: The primary efficacy analysis revealed that both the 12.5-mg and the 25-mg paroxetine CR treatment groups were associated with significant therapeutic effects (change in HAM-D score) from baseline to study endpoint (LOCF: p = .038, 95% CI = -3.38 to -0.09 and p = .005, 95% CI = -4.06 to -0.74, respectively). Results from the Wilcoxon rank sum test of the depressed mood item of the HAM-D (p = .011, 95% CI = -0.57 to -0.07) demonstrated significant efficacy in the 25-mg treatment group but not in the 12.5-mg group. However, LOCF analysis of the CGI-S revealed significant therapeutic effects for both the 12.5-mg (p = .018, 95% CI = -0.61 to -0.06) and 25-mg (p < .001, 95% CI = -0.78 to -0.22) treatment groups. Significantly more patients in the 25-mg paroxetine CR-treated group than in the placebo-treated group met criteria for response (CGI-Improvement score of 1 or 2, p = .035, OR = 1.68, 95% CI = 1.04 to 2.73) as well as for remission (HAM-D score

Efficacy of controlled-release paroxetine in the treatment of late-life depression.

BACKGROUND: Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition. METHOD: In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score. RESULTS: The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo. CONCLUSION: Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.

Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression.

BACKGROUND: Antidepressant efficacy may be compromised by early discontinuation of treatment secondary to common, treatment-emergent side effects, including nausea, agitation, and somnolence. Paroxetine controlled-release (CR) was developed to improve general tolerability and, in particular, gastrointestinal tolerability. OBJECTIVE: To determine the antidepressant efficacy and tolerability of paroxetine CR in adult patients 18 to 65 years of age with DSM-IV major depressive disorder. METHOD: Paroxetine CR (25-62.5 mg/day; N = 212) and paroxetine immediate-release (IR; 20-50 mg/day; N = 217) were compared with placebo (N = 211) in the pooled dataset from 2 identical, double-blind, 12-week clinical trials. RESULTS: Both paroxetine CR and paroxetine IR exhibited efficacy in major depressive disorder as assessed by the reduction in 17-item Hamilton Rating Scale for Depression total score compared with placebo. Moreover, depressed mood and psychic anxiety symptoms improved as early as treatment week 1 in the paroxetine CR group compared with the placebo group. After 6 weeks of treatment, response and remission rates were 41.5% and 20.5% for placebo, 52.8% and 29.6% for paroxetine IR, and 58.9% and 34.4% for paroxetine CR, respectively. After 12 weeks of treatment, response and remission rates were 61.2% and 44.0% for placebo, 72.9% and 52.5% for paroxetine IR, and 73.7% and 56.2% for paroxetine CR, respectively. Rates of nausea were significantly lower for paroxetine CR (14%) than for paroxetine IR (23%; p < or = .05) during week 1. Rates of dropout due to adverse events were comparable between paroxetine CR and placebo, while significantly (p = .0008) more patients treated with paroxetine IR withdrew from the study prematurely compared with those treated with placebo. CONCLUSION: Paroxetine CR is an effective and well-tolerated antidepressant exhibiting symptomatic improvement as early as week 1. Paroxetine CR is associated with low rates of early-onset nausea and dropout rates due to adverse events comparable to those of placebo. The clinical improvement seen with paroxetine CR, coupled with its favorable adverse event profile, suggests a benefit for therapeutic outcome with paroxetine CR.

Predictors of response to pharmacotherapy in social anxiety disorder: an analysis of 3 placebo-controlled paroxetine trials.

BACKGROUND: There is increasing evidence that patients with social anxiety disorder (social phobia) respond to treatment with selective serotonin reuptake inhibitors (SSRIs). Response rates to SSRIs in social anxiety disorder have ranged from at least 50% in controlled trials to up to 80% in open trials. To date, however, there has been little information available about predictors of response to treatment in this disorder. METHOD: Data from 3 placebo-controlled multicenter trials of paroxetine in DSM-IV social anxiety disorder (N = 829) were analyzed using logistic regression to determine predictors of response. Demographic (age, sex), physiologic (baseline heart rate, baseline mean arterial pressure), clinical (baseline social anxiety symptom severity, baseline disability, duration of illness), and trial variables (paroxetine dose, treatment duration) were included. RESULTS: Only duration of treatment was a statistically significant predictor of treatment response. Further analysis demonstrated that, in paroxetine-treated patients in particular, many nonresponders at week 8 (46/166; 27.7%) were responders at week 12. CONCLUSION: These data demonstrate that paroxetine is a reasonable choice of treatment in a broad spectrum of patients with social anxiety disorder. An optimal trial of medication should continue beyond 8 weeks.

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.