Pooled analysis of venlafaxine XR efficacy on somatic and psychic symptoms of anxiety in patients with generalized anxiety disorder

We evaluated the relative efficacy of venlafaxine XR on the psychic versus somatic symptoms of anxiety in patients with generalized anxiety disorder as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Data were pooled and analyzed from 1,841 patients with generalized anxiety disorder who participated in five short-term (8-week) double-blind, multicenter, placebo-controlled studies, two of which had long-term (6-month) extensions. Somatic and psychic anxieties were studied using the Hamilton rating scale for anxiety (HAM-A) factor scores. We examined response rates (> or =50% improvement over baseline severity score) in the overall population and in patients with mainly somatic symptomatology at baseline (somatizers). Venlafaxine XR significantly reduced factor scores for both psychic and somatic HAM-A factors compared with placebo, from the first and second weeks of treatment, respectively. Patients treated with venlafaxine XR had significantly higher rates of response than patients receiving placebo on the psychic (58% vs. 38%, P<.001 at week 8; 66% vs. 35% at week 24, P<.001) and somatic (56% vs. 43%, P<.001 at week 8; 67% vs. 47% at week 24, P<.001) factors of the HAM-A. There was a TreatmentxFactor interaction (P<.027) in response rates: Patients treated with venlafaxine showed similar somatic and psychic anxiety response rates, whereas placebo-treated patients showed higher somatic compared with psychic response rates. Somatizers showed similar rates of response to the total population for the somatic factor of the HAM-A in either treatment group. Patients with generalized anxiety disorder treated with venlafaxine XR showed similar absolute rates of response on somatic and psychic symptoms, but relative to patients treated with placebo, more improvement in psychic than somatic symptoms.     

Quetiapine in the treatment of anxiety in patients with bipolar I or II depression: a secondary analysis from a randomized, double-blind, placebo-controlled study

OBJECTIVE: Quetiapine monotherapy shows efficacy in bipolar depression. The analyses in this multicenter, double-blind, randomized, fixed-dose, placebo-controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms in bipolar depression. METHOD: Of 542 outpatients randomly assigned to treatment, 539 with bipolar I (N = 358) or bipolar II (N = 181) disorder experiencing a major depressive episode (DSM-IV) received 8 weeks of quetiapine monotherapy (600 or 300 mg/day) or placebo between September 2002 and October 2003. Anxiety assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and relevant items from the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Depression (HAM-D). Analyses evaluated the pooled dose groups versus placebo. RESULTS: At week 8, quetiapine 600 and 300 mg/day each demonstrated significant improvements in HAM-A total score versus placebo (-10.8 and -9.9 vs. -6.7, p < .001). Quetiapine (pooled doses) significantly improved HAM-A total score from week 1. In bipolar I depression, quetiapine showed significant improvement in HAM-A total score versus placebo (-10.4 vs. -5.1, p < .001). In bipolar I depression, quetiapine also showed significant improvements versus placebo on the HAM-A anxious mood and tension items, HAM-A psychic and somatic subscales, MADRS inner tension item, and HAM-D psychic anxiety item (all p < .001), but not the HAM-D somatic anxiety item. In bipolar II depression, quetiapine reduced the HAM-A total score more than placebo, but the difference was not statistically significant (-9.8 vs. -9.0, p = .473). In bipolar II depression, quetiapine showed significant improvement versus placebo on the HAM-A anxious mood, MADRS inner tension, and HAM-D psychic anxiety items (all p < .01). CONCLUSION: Quetiapine monotherapy shows efficacy in treating anxiety symptoms in bipolar I depression; however, the anxiolytic effects in bipolar II disorder require further investigation.     

Efficacy of duloxetine for the treatment of generalized anxiety disorder: implications for primary care physicians

Objective: This study examined the efficacy and tolerability of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, for the treatment of patients with generalized anxiety disorder (GAD).Method: Patients were ≥ 18 years old and recruited from 5 European countries, the United States, and South Africa. The study had a 9-week, multicenter, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group design. A total of 513 patients (mean age = 43.8 years; 67.8% female) with a DSM-IV-defined GAD diagnosis received treatment with duloxetine 60 mg/day (N = 168), duloxetine 120 mg/day (N = 170), or placebo (N = 175). The primary efficacy measure was the Hamilton Rating Scale for Anxiety (HAM-A) total score. Secondary measures included the Sheehan Disability Scale, HAM-A psychic and somatic anxiety factor scores, and HAM-A response, remission, and sustained improvement rates. The study was conducted from July 2004 to September 2005.Results: Both groups of duloxetine-treated patients demonstrated significantly greater improvements in anxiety symptom severity compared with placebo-treated patients as measured by HAM-A total score and HAM-A psychic and somatic anxiety factor scores (p values ranged from ≤ .01 to ≤ .001). Duloxetine-treated patients had greater functional improvements in Sheehan Disability Scale global and specific domain scores (p ≤ .001) than placebo-treated patients. Both duloxetine doses also resulted in significantly greater HAM-A response, remission, and sustained improvement rates compared with placebo (p values ranged from ≤ .01 to ≤ .001). The rate of study discontinuation due to adverse events was 11.3% for duloxetine 60 mg and 15.3% for duloxetine 120 mg versus 2.3% for placebo (p ≤ .001).Conclusion: The results of this study demonstrate that duloxetine 60 mg/day and 120 mg/day were efficacious and well tolerated and thus may provide primary care physicians with a useful pharmacologic intervention for GAD.Clinical Trials Registration: ClinicalTrials.gov identifier NCT00122824.     

Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine

OBJECTIVE: Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD. METHOD: The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint. RESULTS: Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly-greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%. CONCLUSION: Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.     

Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder.

BACKGROUND: The efficacy of anxiolytic drugs in generalized anxiety disorder (GAD) is conventionally assessed by evaluating changes in the total score of psychometric scales such as the Hamilton Rating Scale for Anxiety (HAM-A). The purpose of this pooled analysis of data was to evaluate the efficacy of venlafaxine extended release (XR) on individual items of the HAM-A and the Brief Scale for Anxiety (BSA). METHOD: Data were pooled from 5 studies of patients with GAD who were treated with either venlafaxine XR or placebo for 8 weeks (N = 2,021) and up to 6 months (N = 767). Individual items of the HAM-A and the BSA were examined. and, using the mean changes from baseline to endpoint, an effect size for each item was calculated by dividing the difference between baseline and endpoint values for each item by the standard deviation of this difference. The effect sizes determined for the venlafaxine group were compared with those for the placebo group. Items from each scale that are concordant with the DSM-IV diagnostic criteria for GAD were selected for further examination, and the specific effect sizes of each item were expressed after controlling for placebo effects. RESULTS: The effect size of the majority of the 14 items of the HAM-A scale and the 10 items of the BSA scale associated with treatment with venlafaxine XR was greater than with placebo at both 8 weeks and 6 months. Furthermore, the effect sizes at 6 months were generally greater than at 8 weeks in venlafaxine XR-treated patients. Effect sizes associated with venlafaxine XR were greatest for the HAM-A items that were most closely related to diagnostic symptoms of GAD, namely anxious mood, tension, intellectual functioning, and behavior at interview at both 8 weeks and 6 months. Similarly, GAD-related BSA items of inner tension, worrying over trifles, hostile feelings, and muscular tension were associated with the greatest improvements with venlafaxine XR at both time-points. CONCLUSION: The HAM-A and BSA items that most closely corresponded to DSM-IV diagnostic criteria for GAD showed the largest improvement during treatment with venlafaxine XR. This indicates that the specific symptoms of GAD can be treated effectively with venlafaxine XR, both in the short and longer term.     

Silexan in anxiety disorders: Clinical data and pharmacological background

Objectives: Silexan is a lavender oil preparation available in 80-mg capsules. Here we review clinical trials investigating its anxiolytic efficacy, safety and tolerability in humans, as well as preclinical investigations supporting this therapeutic use.

Methods: Besides three selected publications reporting preclinical investigations, seven clinical trials are included, of which five had a treatment duration of 6 or 10 weeks. Primary outcome measure was the HAM-A total score reduction, while single items were assessed with regard to effects on concomitant depressive symptoms and on quality of sleep.

Results: In patients with subthreshold (subsyndromal) anxiety or generalised anxiety disorder (GAD), an anxiolytic effect of Silexan was evident after 2 weeks. HAM-A total score reductions between baseline and end of treatment were significantly superior to placebo in patients with subthreshold anxiety and comparable with those achieved under lorazepam or paroxetine in patients with GAD. In addition, Silexan had beneficial effects on typical concomitant symptoms of anxiety disorders, such as impaired sleep, somatic complaints, co-morbid depression or decreased quality of life. Except for mild gastrointestinal symptoms, Silexan did not induce any adverse effects and did not cause drug interactions, sedation or withdrawal symptoms at daily doses of 80 or 160?mg.

Conclusions: Silexan is a safe and effective treatment in anxiety disorders.     

Paroxetine efficacy in the treatment of generalized anxiety disorder

Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2′-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2′-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2′-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2′-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.     

Efficacy of sertraline in a 12-week trial for generalized anxiety disorder

OBJECTIVE: Sertraline's efficacy and tolerability in treating generalized anxiety disorder were evaluated. METHOD: Adult outpatients with DSM-IV generalized anxiety disorder and a total score of 18 or higher on the Hamilton Anxiety Rating Scale were eligible. After a 1-week single-blind placebo lead-in, patients were randomly assigned to 12 weeks of double-blind treatment with placebo (N=188, mean baseline anxiety score=25) or flexible doses (50-150 mg/day) of sertraline (N=182, mean anxiety score=25). The primary outcome measure was baseline-to-endpoint change in the Hamilton anxiety scale total score. A secondary efficacy measure was the Clinical Global Impression (CGI) improvement score; response was defined as a score of 2 or less. RESULTS: Sertraline patients had significantly greater improvement than placebo patients on all efficacy measures at week 4. Analysis of covariance of the intent-to-treat group at endpoint (with the last observation carried forward) showed a significant difference in the decrease from baseline of the least-square mean total score on the Hamilton anxiety scale between sertraline (mean=11.7) and placebo (mean=8.0). Significantly greater endpoint improvement with sertraline than placebo was obtained for mean scores on the Hamilton anxiety scale psychic factor (6.7 versus 4.1) and somatic factor (5.0 versus 3.9). The rate of responders, based on CGI improvement and last observation carried forward, was significantly higher for sertraline (63%) than placebo (37%). Sertraline was well tolerated; 8% of patients versus 10% for placebo dropped out because of adverse events. CONCLUSIONS: Sertraline appears to be efficacious and well tolerated in the treatment of generalized anxiety disorder.     

Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder

BACKGROUND: A subset of patients with comorbid major depressive disorder and generalized anxiety disorder (GAD) was examined from a double-blind. placebo-controlled study comparing the efficacy and safety of venlafaxine extended release (XR) and fluoxetine. METHOD: From a total of 368 patients, 92 patients meeting DSM-IV criteria for major depressive disorder who also had comorbid GAD were identified. The comparison group comprised 276 evaluable noncomorbid patients. Patients received venlafaxine XR (75-225 mg/day), fluoxetine (20-60 mg/day), or placebo for 12 weeks. Efficacy evaluations included Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions (CGI) scale. RESULTS: By the final assessment at week 12, comorbid patients in the venlafaxine XR group, but not in the fluoxetine group, showed a significantly greater decrease than those in the placebo group in the primary efficacy variables of mean HAM-D and HAM-A total scores (p < .05, pairwise comparison). In comorbid patients, significant pairwise differences were noted between venlafaxine XR and placebo at week 12 for the secondary variables of HAM-D anxiety-somatization and retardation factors, HAM-D depressed mood item. HAM-A psychic anxiety factor, the Hospital Anxiety and Depression scale (HAD) anxiety subscale score, and the Covi Anxiety Scale score. Fluoxetine was significantly different from placebo only on the HAD depression subscale score. Response, defined as > or = 50% decrease in symptoms score, was achieved in 66% and 59% of the comorbid patients for HAM-D and HAM-A, respectively, in the venlafaxine XR group at week 12. This response was higher than that seen with fluoxetine (52% and 45%) or placebo (36% and 24%). Onset of efficacy appeared to be slower in comorbid than in noncomorbid patients. CONCLUSION: This is the first evidence from a controlled study of the effectiveness of pharmacotherapy in patients with comorbid major depressive disorder and GAD. The delayed improvement in comorbid patients compared with noncomorbid patients suggests that a longer treatment period may be necessary in comorbid patients.     

Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial.

BACKGROUND: The objective of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with generalized anxiety disorder (GAD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 8 weeks. The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Sheehan Disability Scale (SDS). The proportions of patients fulfilling response and remission criteria at week 8 were also determined. RESULTS: The intent-to-treat population included 324 patients. At week 8, compared with the placebo group (N = 163), the paroxetine group (N = 161) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables. On the HAM-A anxious mood item, which encompasses the cardinal symptoms of GAD, significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain "social life" as early as week 4 for paroxetine compared with placebo. In both the last-observation-carried-forward and completer data sets, significantly greater proportions of paroxetine-treated patients achieved response or remission by week 8. Treatment with paroxetine was well tolerated, and the number and type of adverse events recorded in the paroxetine group correspond to the known safety profile of this medication. CONCLUSION: Paroxetine in doses of 20 to 50 mg once daily is effective in the treatment of patients with GAD. Improvement of core symptoms of GAD occurs early and is associated with significant reduction in disability after only 8 weeks of treatment.     

Impact of gastrointestinal symptom severity on response to venlafaxine extended-release in patients with generalized anxiety disorder

BACKGROUND: This retrospective analysis evaluated the prevalence and severity of pre-treatment gastrointestinal (GI) symptoms in patients with generalized anxiety disorder (GAD), the impact of these GI symptoms on the efficacy and tolerability of venlafaxine extended-release (XR), and the effect of treatment on prestudy GI symptoms. METHOD: Data from 1932 nondepressed GAD patients were pooled from 5 randomized, double-blind, placebo-controlled studies of venlafaxine XR clinically conducted between May 1995 and December 1997. The GI symptom severity at baseline was estimated from item 11 on the Hamilton Rating Scale for Anxiety (HAM-A). Patients with a GI symptom severity score < or = 2 (moderate or less) and those with a GI symptom severity score > 2 (severe/very severe) were compared for baseline characteristics and short-term (8-week) and long-term (24-week) outcomes. RESULTS: At baseline, for all randomized patients with a HAM-A item 11 score, GI symptoms were rated moderate or lower in 82.8% of patients (GI-low) and severe/very severe in 17.2% (GI-high). The GI-high subgroup was statistically significantly (p < .05) younger, had a longer duration of GAD, and had higher mean HAM-A total scores than the GI-low subgroup. Compared with placebo, venlafaxine XR significantly reduced HAM-A total and psychic anxiety factor scores, regardless of baseline GI symptom severity. The incidence of adverse events, particularly nausea, was higher for the GI-high versus GI-low subgroup. CONCLUSION: Baseline severity of GI symptoms correlated with overall severity of GAD but had no impact on treatment outcome with venlafaxine XR. These data do not support the hypothesis that high baseline GI symptom severity has a negative effect on treatment with venlafaxine XR in GAD 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.     

Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.

BACKGROUND: The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder. METHOD: Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD). RESULTS: The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups. CONCLUSION: Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.     

Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies.

This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM-A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder.

OBJECTIVE: The study compared the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor, and placebo in the treatment of generalized anxiety disorder in children and adolescents. METHOD: The study subjects were 22 children and adolescents age 5-17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children-Revised and who had a Hamilton Anxiety Rating Scale score > or = 16. The patients underwent a 2-3-week prestudy evaluation period, followed by a 9-week double-blind treatment phase in which they were randomly assigned in blocks of four to receive either sertraline or pill placebo. The maximum dose of sertraline was 50 mg/day. Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale. RESULTS: The Hamilton anxiety scale total score, psychic factor, and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4. Self-report measures reflected these results at the end of treatment. CONCLUSIONS: The results of this double-blind, placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents.     

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.     

Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D) total and item scores were analyzed at different treatment times up to 6 weeks. Venlafaxine and fluoxetine both produced statistically significant higher response and remission rates compared with placebo starting from week 2 for response and weeks 3 to 4 for remission. Venlafaxine was statistically significantly superior to fluoxetine from week 3 until week 6 in respect of response rate, and from week 2 until week 6 for remission rate. After 1 week of treatment, greater improvement in individual symptoms was observed in the depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement in psychic anxiety was statistically significantly greater with venlafaxine than with fluoxetine. The presence of baseline psychic anxiety correlated significantly to treatment outcome when analyzing the remission rates. In depressed patients with moderate anxiety (HAM-D psychic anxiety score < or = 2), venlafaxine statistically significantly increased remission rates compared with placebo from week 4 until week 6, while a significant effect of fluoxetine on remission rates was observed starting at week 6. Remission rates in the severely anxious depressed patients (score > 2) were statistically significantly higher with venlafaxine than placebo starting from week 3 until the end of the study period, but no difference could be observed between fluoxetine and placebo. Baseline severity of psychic anxiety had a significant impact on remission rates after treatment of patients diagnosed with depression. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety as early as week 1 compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression.     

A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder.

This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups. These non-positive results were thought to be due to the very high placebo response observed in some centres. To understand the variability of the study, a secondary preplanned analysis was performed. This involved sub-dividing the study centres according to their ability to detect a two-point mean difference between diazepam and placebo at week 8 on the HAM-A total score. Centres able to show such a difference were termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR-treated patients from verum-sensitive centres were significantly greater than in placebo on each of the primary efficacy measures (P 相似文献   

Social adjustment in generalised anxiety disorder: a long-term placebo-controlled study of venlafaxine extended release.

The objective of this analysis was to evaluate the short- (8 weeks) and long-term (24 weeks) efficacy of three fixed doses of venlafaxine extended release (ER) and placebo on the social adjustment of patients with generalised anxiety disorder (GAD). We analysed data from 544 outpatients who participated in a 24-week, double-blind, multicentre, parallel-group, placebo-controlled study conducted at 55 centres in five countries. All patients meet the DSM-IV criteria for GAD and were randomly assigned to receive venlafaxine ER 37.5, 75, and 150 mg or matched placebo administered orally once daily. Social adjustment was measured using the Social Adjustment Scale-Self Report, which explores social adaptation in the areas of work, social and leisure, extended family, primary relationship (marital), parental, and family unit. At baseline, the GAD patients had a high level of social dysfunction. Venlafaxine ER showed a dose-related improvement in social impairment during short-term treatment and in sustaining this improvement over the long-term. In the most severely socially impaired subgroup, placebo remission rates on the HAM-A were low, and the magnitude of the venlafaxine-placebo difference on the mean HAM-A total score was high, reaching more than 7 points. The benefits of venlafaxine ER treatment of GAD extend beyond that of improvement of anxiety symptoms to a significant improvement in the impairment of functioning that is associated with the illness.     

Escitalopram in the treatment of anxiety symptoms associated with depression

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.