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.     

Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention

Pregabalin is the first anxiolytic pharmacologic alternative for the treatment of generalized anxiety disorder (GAD) to be introduced in more than 10 years. GAD is a significant psychiatric condition with lifetime prevalence rates ranging between 5.7 and 6.4%. It causes significant impairment in quality of life and functional abilities equivalent to those associated with major depression. Randomized, controlled trials confirm that pregabalin is superior to placebo and comparable with lorazepam, alprazolam and venlafaxine for the treatment of patients with moderate-to-severe GAD. The onset of anxiolytic activity for pregabalin is apparent within 1 week following initiation of treatment, which is more rapid than that obtained with paroxetine and venlafaxine. Additionally, pregabalin has demonstrated potential for the prevention of relapse of GAD. Recently, the efficacy, safety and tolerability of pregabalin were also shown in a placebo-controlled study with elderly patients. Safety and tolerability profiles are favorable, with transient dizziness and somnolence of mild-to-moderate severity being the most commonly reported adverse events. Pregabalin has minimal potential for drug-drug interactions and does not provoke a clinically significant withdrawal response. Furthermore, pregabalin has low potential for abuse and dependence, unlike other classes of medications used for the treatment of GAD. Clinicians may consider the use of pregabalin in lieu of benzodiazepines as an alternative therapy for their patients with GAD.     

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.     

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.     

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   

Randomized placebo-controlled trial of escitalopram and venlafaxine XR in the treatment of generalized anxiety disorder

Generalized anxiety disorder (GAD) is a highly prevalent and disabling condition. Escitalopram and venlafaxine extended release (XR) both are indicated for the treatment of GAD. Outpatients (ages 18-65 years) with DSM-IV-defined GAD (Hamilton Anxiety Scale [HAMA] >or=20) were eligible to participate in this randomized, double-blind, placebo-controlled, multicenter, flexible-dose trial. Following randomization, patients received 8 weeks of double-blind treatment with escitalopram (10-20 mg/day; N=127), venlafaxine XR (75-225 mg/day; N=129), or placebo (N=136). The primary efficacy parameter was mean change from baseline at week 8 in HAMA total score, using the Last Observation Carried Forward (LOCF) approach. Secondary efficacy parameters were HAMA psychic anxiety subscale, Clinical Global Impressions of Severity (CGI-S) and Improvement (CGI-I) scales. Treatment was completed by 77% of patients. The least square mean difference for change from baseline at week 8 in HAMA total score for escitalopram and venlafaxine XR versus placebo were -1.52 (P=.09) and -2.27 (P=.01), respectively, for LOCF, and -1.92 (P=.033) and -3.02 (P=.001), respectively, for Observed Cases (OC). On all secondary parameters, both active treatments were significantly superior to placebo on the LOCF and OC analyses. Discontinuation due to adverse events was not different for escitalopram versus placebo (7 versus 5%, P=.61), but was significantly greater for venlafaxine XR (13%) versus placebo (P=.03). Venlafaxine XR, but not escitalopram, separated from placebo on the primary efficacy measure, using the LOCF approach. However, overall efficacy analyses suggest that escitalopram and venlafaxine XR are both effective treatments for GAD. Escitalopram was better tolerated.     

Open-label trial of riluzole in generalized anxiety disorder

OBJECTIVE: There is a need to identify novel pharmacotherapies for anxiety disorders. The authors examined the safety and efficacy of riluzole, an antiglutamatergic agent, in adult outpatients with generalized anxiety disorder. METHOD: In an 8-week, open-label, fixed-dose study, 18 medically healthy patients with DSM-IV generalized anxiety disorder received treatment with riluzole (100 mg/day) following a 2-week drug-free period. The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) score at endpoint. RESULTS: Twelve of the 15 patients who completed the trial responded positively to riluzole. At 8 weeks, eight of the 15 patients had HAM-A score indicating remission of their anxiety. The median time to response was 2.5 weeks. CONCLUSIONS: Riluzole appears to be an effective, well-tolerated, and rapidly acting anxiolytic medication for some patients with generalized anxiety disorder. Larger, placebo-controlled studies are indicated.     

Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial

Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV-defined GAD diagnosis were randomized to duloxetine 60-120 mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction > or =50% from baseline), Clinician Global Impression-Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD.     

Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial

Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.     

Metacognitive therapy for generalized anxiety disorder: an open trial

Generalized anxiety disorder (GAD) responds only modestly to existing cognitive-behavioural treatments. This study investigated a new treatment based on an empirically supported metacognitive model [Wells, (1995). Metacognition and worry: A cognitive model of generalized anxiety disorder. Behavioural and Cognitive Psychotherapy, 23, 301-320; Wells, (1997). Cognitive therapy of anxiety disorders: A practice manual and conceptual guide. Chichester, UK: Wiley]. Ten consecutive patients fulfilling DSM-IV criteria for GAD were assessed before and after metacognitive therapy, and at 6, and 12-month follow-up. Patients were significantly improved at post-treatment, with large improvements in worry, anxiety, and depression (ESs ranging from 1.04-2.78). In all but one case these were lasting changes. Recovery rates were 87.5% at post treatment and 75% at 6 and 12 months. The treatment appears promising and controlled evaluation is clearly indicated.     

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.     

Botulinum toxin treatment of social anxiety disorder with hyperhidrosis: a placebo-controlled double-blind trial

OBJECTIVE: Given the often prominent and persistent nature of hyperhidrosis in social anxiety disorder (SAD), to compare botulinum toxin type A to placebo for generalized SAD with hyperhidrosis, in combination with paroxetine. METHOD: Adults with severe axillary hyperhidrosis who met DSM-IV criteria for generalized SAD were randomly assigned to receive 1-time, bilateral, intradermal injections with either botulinum toxin type A or placebo (50 units/axilla). All subjects also received 8 weeks of open-label treatment with paroxetine. The primary outcome measure was the Hyperhidrosis Disease Severity Scale (HDSS). Secondary measures included the Hyperhidrosis Impact Questionnaire, Brief Social Phobia Scale, Liebowitz Social Anxiety Scale, Social Phobia Inventory, and Sheehan Disability Scale. Enrollment occurred from June 2002 to July 2004. RESULTS: Forty subjects were randomly assigned to treatment and included in the analyses. Response rates were 75% (15/20) for botulinum toxin type A versus 15% (3/20) for placebo on the HDSS (p < .001). Botulinum toxin type A produced significantly more improvement in many daily activities that had been limited (p < .01), as well as greater improvement in work and social functioning and in overall disability (p < .05). Botulinum toxin type A was well tolerated, as was paroxetine. CONCLUSION: Botulinum toxin is effective in reducing hyperhidrosis disability and limitations in everyday activities when given in association with paroxetine to subjects with SAD. While further assessment of botulinum toxin type A in SAD is recommended, including a trial of botulinum toxin type A monotherapy, the results suggest that this well-tolerated treatment deserves further consideration in overall management of SAD accompanied by hyperhidrosis.     

Effectiveness of therapeutic massage for generalized anxiety disorder: a randomized controlled trial

Background: Although massage is one of the most popular complementary and alternative medical (CAM) treatments for anxiety, its effectiveness has never been rigorously evaluated for a diagnosed anxiety disorder. This study evaluates the effectiveness of therapeutic massage for persons with generalized anxiety disorder (GAD). Methods: Sixty‐eight persons with GAD were randomized to therapeutic massage (n=23), thermotherapy (n=22), or relaxing room therapy (n=23) for a total of 10 sessions over 12 weeks. Mean reduction in anxiety was measured by the Hamilton Anxiety Rating Scale (HARS). Secondary outcomes included 50% reduction in HARS and symptom resolution of GAD, changes in depressive symptoms (Patient Health Questionnaire (PHQ‐8)), worry and GAD‐related disability. We compared changes in these outcomes in the massage and control groups posttreatment and at 6 months using generalized estimating equation (GEE) regression. Results: All groups had improved by the end of treatment (adjusted mean change scores for the HARS ranged from −10.0 to −13.0; P<.001) and maintained their gains at the 26‐week followup. No differences were seen between groups (P=.39). Symptom reduction and resolution of GAD, depressive symptoms, worry and disability showed similar patterns. Conclusions: Massage was not superior to the control treatments, and all showed some clinically important improvements, likely due to some beneficial but generalized relaxation response. Because the relaxing room treatment is substantially less expensive than the other treatments, a similar treatment packaged in a clinically credible manner might be the most cost effective option for persons with GAD who want to try relaxation‐oriented CAM therapies. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

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   

Cognitive behavior therapy for generalized social anxiety disorder in adolescents: a randomized controlled trial

Early identification and treatment of social anxiety disorder (SAD) is critical to prevent development of a chronic course of symptoms, persistent functional impairment, and progressive psychiatric comorbidity. A small but growing literature supports the effectiveness of cognitive behavior therapy (CBT) for anxiety disorders, including SAD, in adolescence. The present randomized controlled trial evaluated the efficacy of group vs. individual CBT for adolescents with generalized SAD in relation to an educational/supportive psychotherapy that did not contain specific CBT elements. All three treatments were associated with significant reductions in symptoms and functional impairment, and in improved social skills. No differences between treatments emerged on measures of symptoms, but the CBT conditions demonstrated greater gains on behavioral measures. The implications of the findings are discussed.     

Cognitive processes of generalized anxiety disorder in comorbid generalized anxiety disorder and major depressive disorder

This study examines how cognitive variables, which play a central role in the development and maintenance of generalized anxiety disorder (GAD), manifest themselves when GAD and major depressive disorder (MDD) are comorbid. Thirty-two participants were divided into two groups, a group of individuals with a principal diagnosis of comorbid GAD and MDD and a group of people with a principal diagnosis of GAD without MDD. Groups were compared using four cognitive variables: intolerance of uncertainty, poor problem orientation, cognitive avoidance, and beliefs about worry. Our results show that the group of individuals with a principal diagnosis of comorbid GAD and MDD were more intolerant of uncertainty, presented poorer problem orientation, and displayed more cognitive avoidance. The cognitive implications of these results are discussed, and diagnostic criteria are presented to facilitate the differential diagnosis between both groups.