Pindolol potentiation of paroxetine for generalized social phobia: a double-blind, placebo-controlled, crossover study

OBJECTIVE: The effectiveness of pindolol as an adjunctive treatment to boost response to selective serotonin reuptake inhibitors (SSRIs) in patients with generalized social phobia was tested. METHOD: A double-blind, placebo-controlled, crossover design was used to compare addition of 5 mg of pindolol t.i.d. or placebo for 4 weeks to a steady paroxetine dose. Subjects were 14 patients with generalized social phobia who were less than "very much improved" on the Clinical Global Impression scale after at least 10 weeks of treatment with a maximally tolerated dose of paroxetine. Changes on the Liebowitz Social Anxiety Scale and the Social Phobia Inventory scores were compared across the two crossover periods. RESULTS: Pindolol was not significantly superior to placebo for augmenting the effects of paroxetine on social anxiety symptoms. None of the 14 subjects was deemed a responder to the pindolol arm of the crossover. CONCLUSIONS: Pindolol was no more effective than placebo in augmenting the effects of SSRI treatment for generalized social phobia.     

Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study.

OBJECTIVE: The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder). METHOD: In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of "much improved" or "very much improved" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale. RESULTS: The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe. CONCLUSIONS: These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia.     

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   

A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder

OBJECTIVE: Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram. METHOD: A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS: Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients (p < .001), resulting in significantly fewer escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo. CONCLUSION: Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.     

Ondansetron treatment in Tourette's disorder: a 3-week, randomized, double-blind, placebo-controlled study

OBJECTIVE: The aim of the present study was to evaluate the efficacy of ondansetron, a selective 5-HT(3) antagonist, in the treatment of Tourette's disorder. METHOD: Participants (N = 30) aged 12 to 46 years, diagnosed with DSM-IV Tourette's disorder and resistant to previous haloperidol treatment, were enrolled in a 3-week, randomized, double-blind, placebo-controlled outpatient study. Assessments were conducted at baseline and once a week during the study period. Scales used included the Tourette's Syndrome Global Scale (TSGS), the Yale Global Tic Severity Scale (YGTSS), and the Yale-Brown Obsessive Compulsive Scale. Ondansetron dose was 8, 16, and 24 mg/day in the first, second, and third weeks, respectively. RESULTS: A significant positive effect of ondansetron on tic severity, as assessed by the TSGS, was noted (baseline vs. endpoint: mean +/-SD = 29.62 +/-20.33 vs. 20.58 +/-12.82, p = .002 vs. placebo). However, no significant effect was detected upon assessing ondansetron/ placebo effect on tic severity with the YGTSS (baseline vs. endpoint: mean +/-SD = 24.04 +/-9.44 vs. 17.50 +/-9.48, p = .15 vs. placebo). No change in obsessive-compulsive symptoms was noted in either group. Adverse effects included mild and transient abdominal pain. CONCLUSIONS: Ondansetron may have antitic effects in patients with Tourette's disorder. Large-scale, double-blind studies should further assess the antitic efficacy of ondansetron.     

Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind,placebo-controlled study

BACKGROUND: Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults. METHOD: After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score 相似文献   

Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam

BACKGROUND: Pregabalin inhibits release of excess excitatory neurotransmitters, presumably by binding to the alpha2-delta subunit protein of widely distributed voltage-dependent calcium channels in the brain and spinal cord. OBJECTIVE: To assess the anxiolytic efficacy of pregabalin in patients with generalized anxiety disorder. DESIGN: Double-blind, placebo-controlled, active-comparator trial. Patients were randomized to 4 weeks of treatment with pregabalin, 300 mg/d (n = 91), 450 mg/d (n = 90), or 600 mg/d (n = 89); alprazolam, 1.5 mg/d (n = 93); or placebo (n = 91). SETTING: Psychiatry research and clinic settings. PATIENTS: Outpatients meeting the DSM-IV criteria for generalized anxiety disorder, with a baseline Hamilton Anxiety Rating Scale (HAM-A) total score of 20 or greater. MAIN OUTCOME MEASURES: Change from baseline to end point in total HAM-A score in the pregabalin and alprazolam groups compared with the placebo group. The end point response criterion was 50% or greater reduction in the HAM-A total score. RESULTS: Pregabalin and alprazolam produced a significantly greater reduction in mean +/- SE HAM-A total score at last-observation-carried-forward end point compared with placebo (-8.4 +/- 0.8): pregabalin, 300 mg (-12.2 +/- 0.8, P<.001), 450 mg (-11.0 +/- 0.8, P = .02), and 600 mg (-11.8 +/- 0.8, P = .002), and alprazolam (-10.9 +/- 0.8, P = .02). By week 1 and at last-observation-carried-forward end point, the 3 pregabalin groups and the alprazolam group had significantly (P<.01) improved HAM-A psychic anxiety symptoms compared with the placebo group. Compared with the placebo group, HAM-A somatic anxiety symptoms were also significantly (P<.02) improved by the 300- and 600-mg pregabalin groups, but not by the 450-mg pregabalin (week 1, P = .06; week 4, P = .32) and the alprazolam groups (week 1, P = .21; week 4, P = .15). Of the 5 treatment groups, the 300-mg pregabalin group was the only medication group that differed statistically in global improvement at treatment end point not only from the placebo group but also from the alprazolam group. CONCLUSION: Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients.     

Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study

OBJECTIVE: Although significant advances have been made in recent years in the treatment of generalized anxiety disorder (GAD), many patients remain symptomatic despite ongoing treatment, underscoring the need for adjunctive new treatments to help improve response. METHOD: Forty patients with a primary diagnosis of DSM-IV GAD, who continued to experience GAD symptoms despite current anxiolytic treatment of at least 4 weeks' duration, as evidenced by Hamilton Rating Scale for Anxiety (HAM-A) total score > or = 18 and Clinical Global Impressions-Severity of Illness scale score of moderate or greater, completed a 1-week screening phase and were then randomly assigned to 5 weeks of double-blind adjunctive treatment with placebo or risperidone at flexible doses of 0.5 to 1.5 mg/day. Patients continued to take their anxiolytics throughout the study. The study was conducted from June 2001 through March 2003. RESULTS: Adjunctive risperidone was associated with statistically significant improvements in core anxiety symptoms, as demonstrated by greater reductions in HAM-A total scores (p = .034) and HAM-A psychic anxiety factor scores (p = .047) compared with placebo. Although change scores on other outcome variables, including response rates, were higher in the risperidone group, differences did not achieve statistical significance. CONCLUSION: Study findings suggest that risperidone at low doses may represent a useful tool in the management of symptomatic GAD patients.     

Risperidone for severe tardive dyskinesia: a 12-week randomized, double-blind, placebo-controlled study

BACKGROUND: Risperidone has been reported to alleviate the severity of tardive dyskinesia, but without placebo control, the possibility of spontaneous tardive dyskinesia remission after discontinuing original conventional antipsychotics cannot be excluded. This 12-week randomized, double-blind, placebo-controlled study investigated the effect of risperidone on severe tardive dyskinesia. METHOD: Forty-nine DSM-IV schizophrenia patients with severe tardive dyskinesia were enrolled in the study. After a 4-week washout period, the subjects were randomly assigned to treatment with either risperidone or placebo. The risperidone dose was started at 2 mg/day and gradually increased to 6 mg/day over 6 weeks; the 6-mg/day dose was maintained for the remaining 6 weeks of the study. The subjects were evaluated every 2 weeks with the Abnormal Involuntary Movement Scale (AIMS) and the Extrapyramidal Symptom Rating Scale. The final mental status was assessed with the Brief Psychiatric Rating Scale. RESULTS: Twenty-two subjects in the risperidone group and 20 subjects in the placebo group completed the study; the mean baseline AIMS total score for all subjects was 15.9 +/- 4.6. At the end of the study, the mean AIMS total score decrease was 1.1 +/- 4.8 in the placebo group and 5.5 +/- 3.8 in the risperidone group (p <.05). Fifteen subjects (68%) in the risperidone group and 6 subjects (30%) in the placebo group were responders (p <.05). The risperidone responders had a mean AIMS total score decrease of 7.5 +/- 2.1. More significant tardive dyskinesia improvement among the risperidone group was noted from the eighth week and was mainly demonstrated in the buccolinguomasticatory a rea rather than in choreoathetoid movement of the extremities (p <.001). CONCLUSIONS: Risperidone, 6 mg/day, can improve tardive dyskinesia more significantly than discontinuing antipsychotics in patients with severe tardive dyskinesia, especially in the orofacial areas.     

Study refusal and exclusion from a randomized treatment study of generalized social phobia

We examine treatment exclusion and refusal rates as well as reasons for non-participation in a sub-sample of phone interviews conducted to determine eligibility for a randomized study of treatments for generalized social phobia (GSP). This study compared group comprehensive cognitive behavioral therapy (CCBT) to fluoxetine (FLU), placebo (PLA), or their combination. Results suggest that the major exclusion for the study was due to comorbid depression, followed by having a different diagnosis as primary. Patient refusal to enter the study was also common, with the most frequently reported reason being not wanting to take medication. Notably, few people who refused stated an objection to entering CCBT or PLA. These results suggest that there is a need to develop and evaluate a treatment for social anxiety with comorbid depression and to systematically study reasons for reluctance to take medication among individuals with GSP.     

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.     

A review of 19 double-blind placebo-controlled studies in social anxiety disorder (social phobia).

Nineteen double-blind placebo-controlled studies on the treatment of Social Anxiety Disorder (Social Phobia) are reviewed. Initial trials yielded a high degree of efficacy for phenelzine, a large difference between drug and placebo and a low rate of placebo response. Controlled studies with RIMAs (moclobemide and brofaromine) yielded more moderate levels of efficacy and more pronounced placebo effects. Results of the Liebowitz Social Anxiety Scale (LSAS) permit a comparison of the outcomes of the different controlled trials. Overall, the reduction in the mean total score with various drugs is inferior to 50%, probably because the chronic nature of the disorder is not amenable to drastic changes in short-term trials. Results with the LSAS and other scales justify a ranking of the efficacy of the drugs: Classical MAOIs > SRIs > RIMAs. Two controlled studies with benzodiazepines (clonazepam and bromazepam) would position them together with the SRIs relative to efficacy but with problems associated with unwanted effects and dependence. Controlled studies with SRIs (paroxetine and fluvoxamine) demonstrated very significant differences from placebo. Paroxetine is the SRI most extensively studied in Social Anxiety Disorder with positive therapeutic results.     

A PET provocation study of generalized social phobia

In an investigation of the neural circuits that may mediate the subjective experience of social phobia (SP), six male patients with a primary DSM-IV diagnosis of generalized social phobia watched, in the presence of a group of "communication experts," a videotape of themselves giving an impromptu talk (Exposure condition). In the control Baseline condition, they viewed a videotape of a socially competent stranger giving a talk. Regional cerebral blood flow was measured thrice under each condition. The study revealed significant deactivations from Baseline during Exposure in the right lingual gyrus (BA 18) and in the right medial frontal gyrus (BA 11); significant activations during Exposure were not observed. Deactivation of these regions may reflect a strategy of visual avoidance employed by the patients to dampen their phobic experience.     

Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6-week, double-blind, placebo-controlled study

SETTING: Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation. OBJECTIVES: To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD. PARTICIPANTS AND DESIGN: AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms. CONCLUSIONS: Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.