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.     

Controlled-release paroxetine in the treatment of patients with social anxiety disorder

BACKGROUND: This double-blind, placebo-controlled, flexible-dose study was conducted to investigate the efficacy and tolerability of the controlled-release (CR) formulation of paroxetine in adults with social anxiety disorder. METHOD: Outpatients with a primary diagnosis of social anxiety disorder according to DSM-IV criteria entered a 1-week, single-blind, placebo run-in period. Eligible patients were randomly assigned to receive paroxetine CR (flexible dose of 12.5-37.5 mg/day) or placebo for 12 weeks of treatment. The primary efficacy measures were the change from baseline in Liebowitz Social Anxiety Scale (LSAS) score and the proportion of responders based on Clinical Global Impressions (CGI)-Global Improvement scale score. Data were gathered from September 2001 to July 2002. RESULTS: The intent-to-treat population consisted of 186 patients randomly assigned to paroxetine CR and 184 patients randomly assigned to placebo. Statistically significant differences in favor of paroxetine CR compared with placebo were observed in the change from baseline to week 12 last-observation-carried-forward (LOCF) dataset in LSAS total score (difference = -13.33, 95% confidence interval [CI] = -18.25 to -8.41, p <.001). In the CGI-Global Improvement responder analysis, 57.0% of patients treated with paroxetine CR achieved response (very much improved or much improved), compared with 30.4% of patients treated with placebo at week 12 LOCF (odds ratio = 3.12, 95% CI = 2.01 to 4.83, p <.001). Dropout rates due to adverse events were low and comparable in both treatment groups. CONCLUSION: Paroxetine CR effectively treated the symptoms associated with social anxiety disorder and was well tolerated, with few patients stopping treatment due to adverse events. This favorable tolerability profile may enable more patients to experience the benefits of effective therapy.     

Paroxetine for social anxiety and alcohol use in dual-diagnosed patients.

The objective of this study was to compare the efficacy and tolerability of paroxetine to matched placebo in adults with co-occurring social anxiety disorder and alcohol use disorder. Outcome measures included standardized indices of social anxiety and alcohol use. Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol use disorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in a double-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/d and increased to a target dose of 60 mg/d. There was a significant effect of treatment group on social anxiety symptoms, where patients treated with paroxetine improved more than those treated with placebo on both the Clinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05). On alcohol use, there was not a significant effect of treatment on quantity/frequency measures of drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebo patients were improvers on drinking, P < or = 0.05). This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder in individuals with comorbid alcohol problems, and positive treatment effects can be seen in as little as 8 weeks. Further study is warranted to investigate its utility in helping affected individuals reduce alcohol use.     

Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder

BACKGROUND: Evidence indicates that venlafaxine hydrochloride extended release (ER) effectively ameliorates anxiety symptoms. OBJECTIVES: To evaluate the efficacy, safety, and tolerability of flexible-dose venlafaxine ER compared with placebo in the short-term treatment of generalized social anxiety disorder and, secondarily, to compare paroxetine with venlafaxine ER and paroxetine with placebo. DESIGN: Adult outpatients with DSM-IV generalized social anxiety disorder for 6 months or longer were randomly assigned to receive venlafaxine hydrochloride ER (75-225 mg/d), paroxetine (20-50 mg/d), or placebo for 12 weeks or less at 26 centers in the United States. The primary outcome measure was the total Liebowitz Social Anxiety Scale score. Secondary measures included response (Clinical Global Impression-Improvement score, 1 or 2) rates and Clinical Global Impression-Severity of Illness and Social Phobia Inventory scores. RESULTS: Of 440 patients treated, 413 (93.9%) were included in the last-observation-carried-forward efficacy analysis; of the 429 patients in the safety population, 318 (74.1%) completed the study. Mean daily doses were 201.7 mg (SD, 38.1 mg) of venlafaxine hydrochloride ER and 46.0 mg (SD, 7.9 mg) of paroxetine. Venlafaxine ER treatment was significantly superior to placebo at weeks 1 through 12 on the Liebowitz Social Anxiety Scale and Social Phobia Inventory and at week 2 and weeks 6 through 12 for Clinical Global Impression-Severity of Illness and responder status, and was significantly superior to paroxetine treatment at weeks 1 and 2 for the Social Phobia Inventory (P < .05 for all). Paroxetine treatment was significantly superior to placebo at weeks 3 through 12 on the Liebowitz Social Anxiety Scale, the Clinical Global Impression-Severity of Illness scale, and the Social Phobia Inventory, and at weeks 4 through 12 for response (P < .05 for all). Week 12 response rates were significantly greater for the venlafaxine ER and paroxetine groups (58.6% and 62.5%, respectively) vs the placebo group (36.1%) (P < .001 for both). CONCLUSION: Venlafaxine ER is effective in the short-term treatment of generalized social anxiety disorder, with efficacy and tolerability comparable to paroxetine.     

Paroxetine in social anxiety disorder: a randomized placebo-controlled study.

OBJECTIVE: The aim of this study was to evaluate the utility of paroxetine treatment in social anxiety disorder. METHOD: Previously undiagnosed and untreated subjects with social anxiety disorder (generalized social phobia) were selected from among responders to a newspaper advertisement. They were randomized to double-blind treatment with paroxetine 20-50 mg daily or placebo for 3 months. Outcome measures were self-rated social anxiety and avoidance behaviour, and clinician-rated global assessment of improvement. RESULTS: Significant differences in efficacy between treatments (intent-to-treat analysis: 44 subjects on paroxetine and 48 subjects on placebo) were noted after 4-6 weeks, increasing through the treatment period in the paroxetine group. Nine subjects on paroxetine and 3 subjects on placebo discontinued the treatment due to adverse events. Sexual side-effects were noted by 18 subjects on paroxetine and 4 subjects on placebo. CONCLUSION: Paroxetine was effective in alleviating symptoms and avoidance behaviour in social anxiety disorder.     

Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: randomised, double-blind, placebo-controlled, fixed-dose study

Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder (SAD). The efficacy and tolerability of fixed doses of escitalopram were compared to those of placebo in the long-term treatment of generalised SAD, using paroxetine as an active reference. Patients with a DSM-IV diagnosis of SAD between 18-65 years of age were randomised to 24 weeks of double-blind treatment with placebo (n = 166), 5 mg escitalopram (n = 167), 10 mg escitalopram (n = 167), 20 mg escitalopram (n = 170), or 20 mg paroxetine (n = 169). Based on the primary efficacy parameter, Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 (LOCF), a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg escitalopram and for all doses for the OC analyses. Further improvement in LSAS scores was seen at Week 24 (OC and LOCF), with significant superiority over placebo for all doses of escitalopram, and 20 mg escitalopram was significantly superior to 20 mg paroxetine. Response to treatment (assessed by a Clinical Global Impression-Improvement score < or = 2) was significantly higher for all active treatments than for placebo at Week 12. Clinical relevance was supported by a significant decrease in all the Sheehan disability scores, and the good tolerability of escitalopram treatment. It is concluded that doses of 5-20 mg escitalopram are effective and well tolerated in the short- and long-term treatment of generalised SAD.     

Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study.

OBJECTIVE: This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD). METHOD: Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response ("very much improved" or "much improved") for global improvement on the Clinical Global Impression scale. RESULTS: Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated. CONCLUSIONS: Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD.     

Efficacy and tolerability of paroxetine for the long-term treatment of generalized anxiety disorder

BACKGROUND: Paroxetine has demonstrated efficacy in depression and anxiety disorders, including generalized anxiety disorder (GAD). This 32-week study evaluated the maintained efficacy and safety of paroxetine in GAD by assessing the potential for relapse after discontinuation of medication. METHOD: Adults (N = 652) with DSM-IV GAD and a Clinical Global Impressions-Severity of Illness (CGI-S) score > or = 4 received paroxetine (20-50 mg/day) for 8 weeks. Patients whose CGI-S score had decreased by at least 2 points to < or = 3 at week 8 were randomly assigned to double-blind treatment with paroxetine (N = 278) or placebo (N = 288) for a further 24 weeks. The primary efficacy parameter was the proportion of patients relapsing (an increase in CGI-S score of at least 2 points to a score < or = 4 or withdrawal resulting from lack of efficacy) during double-blind treatment. RESULTS: Significantly fewer paroxetine than placebo patients relapsed during the 24-week double-blind phase (10.9% vs. 39.9%; p <.001). Placebo patients were almost 5 times more likely to relapse than paroxetine patients (estimated hazard ratio = 0.213 [95% CI = 0.1 to 0.3]; p <.001). Statistical significance in favor of paroxetine was demonstrated for all secondary efficacy parameters, including functional status. Twice as many paroxetine patients as placebo patients (73%) achieved remission. Paroxetine was well tolerated, with no unexpected adverse events reported. CONCLUSION: Paroxetine was found to be effective and well tolerated for both the short- and long-term treatment of DSM-IV GAD. Continued treatment with paroxetine significantly reduced the potential for relapse of GAD symptoms.     

Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder

OBJECTIVE: To assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of adults with panic disorder. METHOD: Paroxetine CR (25-75 mg/day; N = 444) was compared with placebo (N = 445) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical, double-blind, placebo-controlled, 10-week clinical trials that were pooled for analysis. RESULTS: Paroxetine CR was statistically superior to placebo in the primary outcome measure, percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint. Of the total population that completed or prematurely terminated treatment, 63% and 53% of paroxetine CR-and placebo-treated patients, respectively, were panic-free during the final 2 weeks (p < .005; odds ratio [OR] = 1.63; 95% CI = 1.21 to 2.19). For week 10 completers (72% of total), 73% and 60% of paroxetine CR- and placebo-treated patients, respectively, were panic-free at week 10 (p < .005; OR = 2.11; 95% CI = 1.45 to 3.07). Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale. Adverse events leading to study withdrawal were minimal and occurred in 11% of the paroxetine CR group and 6% of the placebo group. Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study. There were no unexpected adverse events, and serious adverse events were uncommon (10 [2.3%] of the 444 patients treated with paroxetine CR vs. 8 [1.8%] of the 445 patients treated with placebo). CONCLUSION: Paroxetine CR is an effective and well-tolerated treatment for panic disorder. Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events.     

A randomized controlled trial of venlafaxine extended release in generalized social anxiety disorder

BACKGROUND: Generalized social anxiety disorder is a debilitating psychiatric illness characterized by maladaptive thoughts about social situations. This double-blind study evaluated the anxiolytic efficacy, safety, and tolerability of venlafaxine extended release (ER) in adult out-patients with generalized social anxiety disorder. METHOD: Patients were randomly assigned to receive 12 weeks of treatment with a flexible dose of venlafaxine ER (75 to 225 mg/day) or placebo. The Liebowitz Social Anxiety Scale (LSAS) total score was the primary efficacy variable. Secondary efficacy variables included scores on the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, Social Phobia Inventory (SPIN), and LSAS subscales. Response was defined as a CGI-I score of 1 or 2. Two definitions of remission were used: LSAS total score < or = 30 and CGI-I score of 1. RESULTS: Data from 271 patients (intent-to-treat population) were analyzed for efficacy; 279 patients were analyzed for safety. Overall, 173 patients completed the study. Improvement on the LSAS was significantly greater with venlafaxine ER treatment than with placebo at weeks 6 through 12 (p < .05, weeks 6 and 8; p < .01, week 10; and p < .001, week 12) and at weeks 8 through 12 based on CGI-S and SPIN scores. Week 12 response and remission (LSAS score < or = 30) rates were significantly greater in the venlafaxine ER group than in the placebo group (response: 44% vs. 30%, respectively, p = .018; remission: 20% vs. 7%, respectively, p < .01). Patients experienced no unexpected or serious adverse events. CONCLUSION: Venlafaxine ER is safe, well tolerated, and efficacious in the short-term treatment of generalized social anxiety disorder.     

A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling

BACKGROUND: This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of paroxetine in the treatment of pathological gambling. METHOD: Patients fulfilling DSM-IV criteria for pathological gambling and scoring > or = 5 on the South Oaks Gambling Screen were enrolled if no other Axis I disorder was present. A 1-week placebo run-in phase was followed by 8 weeks' treatment with paroxetine or placebo. The initial paroxetine dose of 20 mg/day could be increased after week 2 by 10 mg/week to a maximum of 60 mg/day. Changes in clinical status were assessed using the Gambling Symptom Assessment Scale (G-SAS) and the Clinical Global Impressions scale (CGI). Treatment-emergent symptoms were assessed weekly. RESULTS: Forty-five patients were included in an intent-to-treat analysis (N = 23 paroxetine, N = 22 placebo). Statistically significantly greater reductions in the total score of the G-SAS were observed in the paroxetine group compared with the placebo group at weeks 6 through 8 (p = .003, .003, and .042, respectively). Improvement on the CGI was also significantly greater in the paroxetine than in the placebo group at the same timepoints (p = .033, .014, and .025, respectively). A significantly greater proportion of patients in the paroxetine group were responders at weeks 7 and 8 (p = .011 and .010, respectively). CONCLUSION: The results of this trial indicate that paroxetine may be effective in the treatment of pathological gambling. There were no unexpected side effects from this treatment. However, additional studies with larger patient samples and a longer treatment phase are required to establish conclusively the efficacy and safety of paroxetine for this indication.     

Tiagabine for the treatment of generalized anxiety disorder: a randomized, open-label, clinical trial with paroxetine as a positive control

BACKGROUND: Gamma-aminobutyric acid (GABA) plays a central role in the pathophysiology of anxiety. Tiagabine, a selective GABA reuptake inhibitor, enhances normal GABA tone. This 10-week, randomized, open-label trial evaluated tiagabine in patients with generalized anxiety disorder (GAD), with paroxetine serving as a positive control. METHOD: Adult patients with DSM-IV GAD were randomly assigned to receive either tiagabine or paroxetine. Tiagabine was initiated at 4 mg/day (2 mg morning and evening) during week 1. Between weeks 2 and 6, the dose was individually titrated in 2-mg increments (maximum increase of 4 mg/week) for optimal response to a maximum dose of 16 mg/day (8 mg morning and evening). During weeks 7 through 10, patients received the dosage determined during the titration period. Paroxetine was initiated at 20 mg nightly for the first week and similarly titrated in 10-mg increments to a maximum dose of 60 mg/day. Assessments included the Hamilton Rating Scale for Anxiety (HAM-A), Hospital Anxiety and Depression Scale (HADS), Hamilton Rating Scale for Depression (HAM-D), Pittsburgh Sleep Quality Index (PSQI), and Sheehan Disability Scale (SDS). RESULTS: Forty patients were enrolled (tiagabine, N = 20; paroxetine, N = 20). Mean final doses were tiagabine 10 mg/day (range, 4-16 mg/day) or paroxetine 27 mg/day (range, 20-40 mg/day). Tiagabine and paroxetine significantly reduced anxiety (HAM-A and HADS total and anxiety subscales). Although patients were not diagnosed with a mood disorder, both tiagabine and paroxetine reduced comorbid depressive symptoms (HAM-D total and HADS total and depressive subscale). Tiagabine and paroxetine significantly improved sleep quality (PSQI) and functioning (SDS). Both tiagabine and paroxetine were well tolerated. CONCLUSION: The selective GABA reuptake inhibitor tiagabine and the positive control paroxetine significantly reduced anxiety and comorbid depressive symptoms, improved sleep quality and functioning, and were well tolerated in patients with GAD. Tiagabine may be a therapeutic option for the treatment of anxiety disorders.     

Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study

BACKGROUND: The efficacy of selective serotonin reuptake inhibitors in the acute treatment of social anxiety disorder (social phobia) is well established. OBJECTIVE: To evaluate whether the efficacy of paroxetine hydrochloride in this disorder is maintained in the long term. METHODS: This was a placebo-controlled multicenter study comprising a single-blind acute treatment phase (12 weeks) and a randomized, double-blind maintenance treatment phase (24 weeks) for patients who had responded to paroxetine during the acute phase. Four hundred thirty-seven adult patients with social anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, code 300.23) entered the acute phase, and 323 continued into the maintenance phase (162 paroxetine and 161 placebo). The principal outcome measure was the proportion of patients relapsing during the maintenance phase. RESULTS: Two hundred fifty-seven patients completed the study (136 paroxetine-treated and 121 placebo-treated patients). Significantly fewer patients relapsed in the paroxetine group than in the placebo group (14% vs 39%; odds ratio, 0.24; 95% confidence interval, 0.14-0.43; P<.001). At the end of the study, a significantly greater proportion of patients in the paroxetine group showed improvement as shown on the Clinical Global Impression global improvement rating compared with the placebo group (78% vs 51%; odds ratio, 3.66; 95% confidence interval, 2.22-6.04; P<.001). Compared with placebo, paroxetine treatment significantly (P<.001) improved the symptoms of social anxiety as shown on the Liebowitz Social Anxiety Scale, Social Phobia Inventory, Sheehan Disability Scale, Symptom Checklist-90 score, and EuroQol visual analogue scale, indicating decreased disability and increased well-being. Paroxetine was well tolerated. CONCLUSION: Paroxetine is an effective long-term treatment for social anxiety disorder.     

Paroxetine treatment of generalized anxiety disorder: a double-blind,placebo-controlled study

OBJECTIVE: This study assessed the efficacy of two fixed doses of paroxetine in the treatment of generalized anxiety disorder. METHOD: Outpatients (N=566) with generalized anxiety disorder and no other axis I disorder were eligible if they scored >/=20 on the Hamilton Rating Scale for Anxiety (with a score of 2 or higher on the anxious mood and tension items). Following a 1-week placebo run-in phase, patients were randomly assigned to 8 weeks of treatment with paroxetine, 20 or 40 mg/day, or placebo. The primary outcome measure was the change from baseline in total score on the Hamilton anxiety scale. Response was defined as a rating of "very much improved" or "much improved" on the Clinical Global Impression global improvement measure; remission was defined as a Hamilton anxiety scale score 相似文献   

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.     

Paroxetine in child and adolescent outpatients with panic disorder.

Paroxetine has repeatedly been shown to be effective in the treatment of panic disorder (PD) in adults, and, according to previous case observations, it may be useful in treating children and adolescents with PD as well. This preliminary naturalistic study examines effectiveness and safety of paroxetine in the treatment of children and adolescents with PD. A chart review was conducted on 18 patients with Diagnostic and Statistical Manual of Mental Disorders PD admitted to the Division of Child Neurology and Psychiatry and to the Department of Psychiatry at the University of Pisa. Paroxetine was given at an initial mean dosage of 8.9 +/- 2.1 mg/day and was gradually increased up to 40 mg/day, depending on clinical response and side effects. Clinical status was assessed with the Clinical Global Impression (CGI) and adverse effects were assessed retrospectively at each visit. Patients with final CGI-Improvement scores of 1 or 2 were considered responders. Mean paroxetine treatment duration was 11.7 +/- 8.3 months, with a mean final dosage of 23.9 +/- 9.8 mg/day (range, 10-40 mg/day). No patient had to interrupt the treatment because of side effects. Fifteen patients (83.3%) were considered responders. The mean change on the CGI-Severity scale was statistically significant (p < 0.0001). Paroxetine was well tolerated and effective in the treatment of PD in these children and adolescents.     

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.     

An open trial of paroxetine for the "offensive subtype" of taijin kyofusho and social anxiety disorder

The taijin kyofusho (TKS) offensive subtype is thought to be a culture-bound syndrome similar to social anxiety disorder (SAD). In Western countries, such patients would be diagnosed as having delusional disorder, somatic subtype, or body dysmorphic disorder. Recently, open trials for the TKS offensive subtype and a randomized controlled trial for body dysmorphic disorder demonstrated that selective serotonin reuptake inhibitors (SSRIs) might be as effective in TKS as in SAD. This study investigated the efficacy of the SSRI paroxetine in patients with the TKS offensive subtype, both on anxiety and fears, as well as insight. This study was a 12-week open trial using paroxetine in 22 patients with TKS. Subjects were diagnosed based on the original diagnostic criteria for the TKS offensive subtype. Insight regarding TKS symptoms was assessed by the 11th supplement subscale "Insight into obsessions and compulsions" of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The Liebowitz Social Anxiety Scale (LSAS), the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), Rosenberg's Self-Esteem Scale, and the Interpersonal Distrust subscale of the Eating Disorder Inventory were also administered. Offensive anxiety was assessed by the original TKS offensive anxiety subscale (0-3 points). The primary efficacy variable was the Clinical Global Impression scale (CGI) global improvement item. Nineteen patients completed the study. Forty-seven percent (9/19) were responders to the drug treatment (scoring 2 or less on the CGI). Last observation carried forward (LOCF) analysis (N=22) demonstrated a statistically significant reduction in LSAS total score and offensive anxiety in TKS, and the insight scale score of the Y-BOCS also significantly improved. Interpersonal distrust showed a trend toward improvement.     

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.     

Paroxetine in the treatment of obsessive-compulsive disorder: randomized, double-blind, placebo-controlled study in Japanese patients

The efficacy of paroxetine in the treatment of obsessive-compulsive disorder in Western populations is well established. The present study compares the efficacy and safety of paroxetine with placebo in the treatment of obsessive-compulsive disorder in Japanese patients. Patients aged 16 years or older who met Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for obsessive-compulsive disorder and had a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of >/=16 were randomized to receive 12 weeks' therapy in a double-blind manner. Paroxetine 20-50 mg/day or placebo was administered following a 1 week, placebo run-in phase. One hundred and ninety-one patients were randomized to either paroxetine or placebo, 188 patients were assessed as the full analysis set (FAS) and 144 patients completed the 12 week study. After adjustment for the Y-BOCS total score at baseline, reductions in obsessive-compulsive total score at week 6 and at the end of therapy were significantly greater in the paroxetine group than the placebo group. Most of the adverse events that occurred during the study were of mild to moderate intensity. Paroxetine is effective and well tolerated in Japanese adult patients with obsessive-compulsive disorder.