Efficacy of pregabalin in preventing relapse in patients with generalized social anxiety disorder: results of a double-blind, placebo-controlled 26-week study

The objective of this study was to evaluate the efficacy and safety of pregabalin in preventing relapse in generalized social anxiety disorder (SAD). Patients with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) generalized SAD, who met responder criteria after 10 weeks of open-label treatment with fixed-dose pregabalin (450 mg/day; n=153), were randomly assigned to 26 weeks of double-blind treatment with pregabalin (450 mg/day) or placebo. The primary a-priori outcome of time to relapse was analyzed using the Kaplan-Meier method and the log-rank test. Double-blind treatment with pregabalin was associated with significant delay in time to relapse versus placebo (P=0.035), and with significantly greater maintenance of symptomatic improvement over 26 weeks on the Liebowitz Social Anxiety Scale total (P=0.012) and subscale scores and on the Marks Fear Questionnaire total phobia (P=0.010) and social phobia (P=0.014) subscales. Pregabalin was generally well tolerated. During the double-blind phase, the adverse events that occurred more frequently with pregabalin compared with placebo were dizziness (11.3 vs. 4.1%) and infection (21.3 vs. 16.4%). The results of this study suggest that pregabalin (450 mg/day) is safe, well tolerated, and has significant relapse-prevention efficacy over 26 weeks in patients with SAD who responded to an initial course of the pregabalin treatment.     

A randomized,double-blind,placebo-controlled,fixed-dose,multicenter study of pregabalin in patients with generalized anxiety disorder

Pregabalin is a novel compound under development for the treatment of several types of anxiety disorders. To obtain an initial evaluation of the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder (GAD), we conducted a double-blind, fixed-dose, parallel-group, placebo and active-controlled multicenter 4-week study that compared 271 patients randomized to receive pregabalin 50 mg tid (N = 70), pregabalin 200 mg tid (N = 66), placebo (N = 67), or lorazepam 2 mg tid (N = 68), followed by a 1-week double-blind taper. The primary efficacy parameter was change from baseline to endpoint (last observation carried forward) in the Hamilton Anxiety Scale (HAM-A) total score; adjusted mean change scores on the HAM-A were significantly improved for pregabalin 200 mg tid (difference of 3.90 between drug and placebo; p = 0.0013 [ANCOVA], df = 252) and for lorazepam (difference of 2.35; p = 0.0483 [ANCOVA], df = 252), with the significant difference between the pregabalin 200 mg tid and placebo groups seen at week 1 of treatment (p = 0.0001 [ANCOVA], df = 238). Safety analysis, which included assessment of spontaneously reported adverse events, laboratory monitoring, and withdrawal symptoms, showed pregabalin to be generally well-tolerated. The most common adverse events seen with pregabalin 200 mg tid were somnolence and dizziness. They were usually mild or moderate in intensity and were often transient. Pregabalin-treated patients had a higher completion rate than lorazepam-treated patients. This study supports the hypothesis that pregabalin is effective and safe in short-term therapy for GAD. More studies are needed to determine the best dosing regimen to optimize efficacy and tolerability.     

Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial

The objective of this study was to evaluate the anxiolytic efficacy, and speed of onset of efficacy, of pregabalin (PGB) and venlafaxine-XR (VXR) in patients with generalized anxiety disorder (GAD). In this double-blind trial, outpatients, ages 18-65 years, who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for GAD were randomized to 8 weeks of flexible-dose treatment with PGB (300-600 mg/day), VXR (75-225 mg/day), or placebo (PBO). The intent-to-treat sample consisted of 121 patients on PGB [least square (LS) mean ± SE baseline Hamilton Anxiety Rating Scale (HAM-A), 27.6 ± 0.4], 125 patients on VXR (baseline HAM-A, 27.4 ± 0.4), and 128 patients on PBO (baseline HAM-A, 26.8 ± 0.4). Treatment with PGB was associated with a significantly greater LS mean change in the HAM-A total score at last observation carried forward endpoint versus PBO (-14.5 ± 0.9 vs. -11.7 ± 0.9; P = 0.028). Treatment with VXR was not significant versus PBO at endpoint (-12.0 ± 0.9; -11.7 ± 0.9; P =0.968). Treatment with PGB showed an early onset of improvement, with significantly greater LS mean change in the HAM-A by day 4 versus both PBO (-5.3 ± 0.5 vs. -3.4± 0.5; P = 0.008) and VXR (-2.9 ± 0.5; P = 0.0012). The proportion of patients reporting a severe adverse event was similar for PGB (9.1%) and PBO (7.8%), but higher for VXR (20.0%; P < 0.05). In conclusion, PGB was a safe and effective treatment of GAD, with a significantly earlier onset of anxiolytic activity than VXR.     

Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study

Pregabalin is a novel compound in development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d. pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P < or = 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder.     

Fluvoxamine treatment of generalized social anxiety disorder in Japan: a randomized double-blind, placebo-controlled study

The efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of social anxiety disorder (SAD) has been reported in the USA and Europe. However, no clinical investigation has been done with SSRIs in Japanese patients with SAD. This study was performed to determine the effectiveness and safety of fluvoxamine for generalized SAD (GSAD) in Japanese patients. In this double-blind study, patients meeting DSM-IV criteria for GSAD were randomized to receive treatment with fluvoxamine or placebo for 10 wk. Fluvoxamine treatment was initiated at 50 mg/d, and increased by 50 mg weekly to a maximum of 150 or 300 mg/d. The primary efficacy outcome was mean change from baseline on the Liebowitz Social Anxiety Scale - Japanese Version (LSAS-J) total score. The secondary outcomes were response according to the Clinical Global Impressions - Global Improvement (CGI-I) score and three domains of the Sheehan Disability Scale (SDS; used to assess psychosocial impairment). A total of 176 fluvoxamine-treated patients and 89 placebo-treated patients were eligible for the efficacy analysis. At week 10, the fluvoxamine-treated patients had a significantly greater reduction in the LSAS-J total score compared with placebo-treated patients (p=0.0197), with significantly more fluvoxamine recipients being at least much improved on the CGI-I scale compared with placebo-treated patients (p=0.024). Fluvoxamine-treated patients also had better responses on the SDS compared with placebo-treated patients (p=0.0208). Fluvoxamine was safe and well tolerated. These results suggest that fluvoxamine is effective for the treatment of Japanese patients with GSAD.     

Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing

Pregabalin is a new anxiolytic that acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the alpha2-delta subunit of voltage-gated calcium channels. The current study evaluated the anxiolytic efficacy of BID versus TID dosing of pregabalin in patients with generalized anxiety disorder. Outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition generalized anxiety disorder and having baseline Hamilton Anxiety (HAM-A) total scores > or =20 were randomized to 6 weeks of double-blind treatment with pregabalin 200 mg/d (BID; N = 78), 400 mg/d (BID; N = 89), or 450 mg/d (TID; N = 88) or placebo (N = 86). Mean improvement in HAM-A total score at last observation carried forward end point was significantly greater on pregabalin 200 (P = 0.006), 400 (P = 0.001), and 450 mg/d (P = 0.005) compared with placebo. Pairwise comparisons of BID versus TID dosing found no difference in HAM-A change score at end point. All 3 pregabalin dosage groups showed significantly greater efficacy versus placebo at end point on the HAM-A psychic and somatic anxiety factor scores. Improvement on both factors was rapid: significance versus placebo was achieved as early as the first assessment at week 1, with > or =30% reduction in HAM-A severity and equal or greater improvement for every subsequent visit in > or =38% of patients in all 3 pregabalin dosage groups (P < or = 0.001). Pregabalin was well tolerated, and despite the fixed-dose study design, discontinuations caused by adverse events ranged from 9% to 13%--comparable with that observed with placebo (8%). This study demonstrates that pregabalin is an effective treatment of generalized anxiety disorder, with BID dosing showing similar efficacy and comparable tolerability with TID dosing.     

Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial

To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients (N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with a benzodiazepine for 8-52 weeks were stabilized for 2-4 weeks on alprazolam in the range of 1-4 mg/day. Patients were then randomized to 12 weeks of double-blind treatment with either pregabalin 300-600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment. Outcome measures included ability to remain benzodiazepine-free (primary) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist (PWC). At endpoint, a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo (51.4% vs 37.0%). Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo (-2.5 vs +1.3; p < 0.001), and lower endpoint mean PWC scores (6.5 vs 10.3; p = 0.012). Thirty patients (53%) in the pregabalin group and 19 patients (37%) in the placebo group completed the study, reducing the power to detect a significant difference on the primary outcome. The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy.     

A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder

Venlafaxine extended release (ER) is a dual serotonin-norepinephrine reuptake inhibitor previously shown to be effective in the treatment of major depressive disorder and generalized anxiety disorder. This placebo-controlled, multicenter, randomized, double-blind trial examined the efficacy and safety of venlafaxine ER in outpatients with generalized social anxiety disorder. Two hundred seventy-two outpatients were randomly assigned to receive either a flexible dose of venlafaxine ER (75 to 225 mg/d) or placebo for 12 weeks. Venlafaxine ER was statistically significantly more effective than placebo as demonstrated by the Liebowitz Social Anxiety Scale total scores at weeks 4 to 12. Scores of both the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales showed that venlafaxine ER was significantly more effective than placebo at weeks 4 to 12. In addition, more venlafaxine ER-treated patients achieved CGI-Improvement scores of 1 or 2 than placebo-treated patients at weeks 4 to 12, demonstrating a greater percentage of responders to venlafaxine ER treatment. Assessment using the fear/anxiety and avoidance subscales of the Liebowitz Social Anxiety Scale and the Social Phobia Inventory Scale also showed venlafaxine ER to be more effective than placebo at weeks 4 to 12 and 6 to 12, respectively. The Sheehan Disability Inventory showed that patients in the venlafaxine ER-treated group had significantly better outcomes in social life at weeks 4 and 12, and in work at week 12. Adverse events were similar to those reported in studies of venlafaxine ER in depression and generalized anxiety disorder. Venlafaxine ER was safe, well tolerated, and efficacious in the short-term treatment of generalized social anxiety disorder.     

Deramciclane in the treatment of generalized anxiety disorder: A placebo-controlled, double-blind, dose-finding study

Deramciclane, a camphor derivative, is a novel anxiolytic agent with a unique mechanism of action. It acts as a potent and specific antagonist at serotonin 5-HT_2A/2C receptors, and exhibits anxiolytic efficacy in animal models. The aim of this double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of a range of doses of deramciclane in patients with generalized anxiety disorder (GAD). Adult patients with a diagnosis of GAD (DSM-IV) and a Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 18; a score ≥ 2 for the HAM-A items ‘Anxious Mood’ and ‘Tension’; a score ≥ 4 on the Clinical Global Impression of Severity of Illness (CGI-S) Scale; and a score ≤ 20 on the Montgomery–Åsberg Depression Rating Scale (MADRS) were enrolled in the study. Following a 1–2 week placebo run-in period, patients were randomized to receive deramciclane (10, 30, or 60 mg/day in two divided doses) or placebo for 8 weeks, followed by a 2-week placebo wash-out period. The primary efficacy measure was change in HAM-A score from baseline to week 8. Adverse events were monitored throughout the study. Withdrawal reactions were assessed at the end of the study (week 8) and during the placebo wash-out period using the Physician's Withdrawal Checklist (34 items). In the intent-to-treat population (n = 208), both the deramciclane 30 mg/day and 60 mg/day doses provided clinically relevant improvements in HAM-A total score after 8 weeks of treatment, reaching statistical significance compared with placebo in the 60 mg/day dose group (p = 0.024) and a clear trend in the 30 mg/day group (p = 0.059). On the HAM-A psychic anxiety factor, significant improvements were seen in patients in the deramciclane 30 mg/day and 60 mg/day treatment groups compared with those in the placebo group (p < 0.05). Adverse events were reported at a similar frequency across all four treatment groups; the most commonly reported adverse event was headache. No withdrawal reactions were observed on abrupt discontinuation of deramciclane. In conclusion, deramciclane 60 mg/day showed significant evidence of efficacy for the treatment of GAD in adult patients. The efficacy for the 30 mg/day dose was close to the larger dose although not significant in the primary analysis, and there was no significant evidence of efficacy for the 10 mg/day dose. Deramciclane was safe and well-tolerated up to the 60 mg/day dose over an 8-week period.     

A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.     

Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine

This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.     

普瑞巴林治疗广泛性焦虑障碍的疗效与安全性的系统评价

目的系统评价普瑞巴林治疗广泛性焦虑障碍(GAD)的临床疗效和安全性。方法电子检索CENTRAL、Pubmed、EMbase和中国生物文献数据库文献(CBM),全面收集普瑞巴林治疗GAD的随机对照试验(RCTs),采用Cochrane系统评价方法评价纳入RCTs的方法学质量后,采用RevMan 5.1.4软件对提取的数据进行分析。结果纳入7个RCTs,共2 410例患者。与安慰剂相比,普瑞巴林150 mg·d~(-1)治疗GAD有效率无统计学差异[RR=1.32,95%CI(0.98,1.79),P=0.07],普瑞巴林固定剂量200～450 mg·d~(-1)[RR=1.60,95%CI(1.34,1.93),P<0.01]、600 mg·d~(-1)[RR=1.42,95%CI(1.18,1.70),P=0.000 2]以及可变剂量组[RR=1.25,95%CI(1.06,1.49),P=0.01]有效率差异均有统计学意义。与安慰剂组相比,普瑞巴林固定剂量组150～450 mg·d~(-1)以及可变剂量组因不良反应退出试验人数差异无统计学意义(分别为P=0.26,P=0.12);而普瑞巴林600 mg·d~(-1)组因不良反应退出试验人数差异有统计学意义[RR=1.76,95%CI(1.16,2.68),P=0.008]。结论普瑞巴林200～450 mg·d~(-1)治疗GAD有效且安全性好。     

Tiagabine in adult patients with generalized anxiety disorder: results from 3 randomized, double-blind, placebo-controlled, parallel-group studies

The objective of these studies was to evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid reuptake inhibitor, in adult patients with generalized anxiety disorder (GAD). Patients with a diagnosis of GAD were enrolled in 1 of 3 randomized, placebo-controlled, 10-week studies. In each study, tiagabine was taken twice daily in divided doses--4, 8, or 12 mg/d in a fixed-dose study and 4-16 mg/d in two flexible-dose trials. The primary efficacy measure was the change from baseline in the 14-item Hamilton Rating Scale for Anxiety (HAM-A) total score at the final visit (last observation carried forward). Additional measures included change from baseline in the anxiety subscale of the Hospital Anxiety and Depression Scale, the Sheehan Disability Scale, and Clinical Global Impressions-Improvement scale. Tolerability was assessed via spontaneous reports as well as rating scales throughout the study period. In all 3 studies, there was no significant differentiation from placebo on the primary measure (change in HAM-A) for any tiagabine dose (P > 0.05). In the 2 flexible-dose studies, the tiagabine group showed improvements over time in the HAM-A that reached significance only in those patients who completed 10 weeks of treatment (study 2, P = 0.018; study 3, P = 0.036). The most common adverse events were dizziness, headache, nausea, fatigue, and somnolence. In conclusion, the results of these studies do not support the efficacy of tiagabine in adult patients with GAD.     

A randomized,double-blind,placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan

Objective This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20?mg/day) in Japanese patients with social anxiety disorder (SAD).

Research design and methods Patients aged 18–64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression–Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10?mg or escitalopram 20?mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10?mg and 20?mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses.

Clinical trial registration This study has the www.japic.or.jp identifier: JapicCTI-121842.

Results For the primary efficacy endpoint, the difference from placebo in the LSAS-J was ?3.9 (p?=?0.089) for escitalopram 10?mg. Since the superiority of escitalopram 10?mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20?mg versus placebo of ?9.8 (p?<?0.001). In pre-specified sensitivity analyses, the difference versus placebo was ?4.9 (p?=?0.035) (ANCOVA, FAS, OC) and ?5.0 (p?=?0.028) (MMRM, FAS) (escitalopram 10?mg) and ?10.1 (p?<?0.001) (ANCOVA, FAS, OC) and ?10.6 (p?<?0.001) (MMRM, FAS) (escitalopram 20?mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder.

Conclusion Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.     

Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study

Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 +/- 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient-completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p less than 0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, -3.4; estazolam, -7.1; p less than 0.001] and without the insomnia item [placebo, -2.7; estazolam, -5.5; p less than 0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action.     

Long-term efficacy of pregabalin in generalized anxiety disorder

A multicenter, randomized, placebo-controlled, double-blind study was conducted to evaluate the efficacy of pregabalin in preventing relapse of generalized anxiety disorder (GAD) after response to short-term treatment. Outpatients (n=624) with GAD for > or =1 year received open-label pregabalin (450 mg/day) for 8 weeks and, if a clinical response was observed, were randomized to receive either pregabalin (450 mg/day; n=168) or placebo (n=170) for 24 weeks. The primary efficacy parameter was time to relapse. Among responders to open-label acute treatment with pregabalin, time to relapse of GAD was significantly longer for patients treated with pregabalin compared with placebo (P<0.0001). Fifty per cent of the placebo group had relapsed by day 23, and at study endpoint, 65% had relapsed. In the pregabalin group, only 42% had relapsed by study end. Total attrition during double-blind treatment was somewhat higher on pregabalin compared with placebo (21.4 vs. 15.3%); attrition owing to adverse events (AEs) was also somewhat higher on pregabalin (6.0 vs. 2.4%). AEs were relatively low in the double-blind phase; only three AEs occurred with an incidence of more than 5% on pregabalin and placebo, respectively: infection (14.9 vs. 11.2%), headache (10.1 vs. 11.2%), and somnolence (6.0 vs. 0%). No safety concerns were identified with long-term treatment. The study indicates that pregabalin is an effective treatment for the prevention of relapse in patients with GAD.     

Adjunctive risperidone in the treatment of generalized anxiety disorder: a double-blind, prospective, placebo-controlled, randomized trial

Background:Residual symptoms despite treatment are common in generalized anxiety disorders (GAD). The Patient-Rated Troubling Symptoms for Anxiety (PaRTS-A) is a newly created and validated instrument that measures the symptoms most troublesome to each individual patient and was used to test the hypothesis that adjunctive risperidone improves residual GAD symptoms. Methods: Primary care and psychiatry clinicians enrolled adults (n = 417) with GAD and a Clinical Global Impressions of Severity rating >/=4 despite >/=8 weeks of anxiolytic treatment. Subjects were randomized to adjunctive risperidone or placebo. The primary endpoint was change from baseline to week 4 endpoint in PaRTS-A. Results: Improvement from baseline to week 4 endpoint in PaRTS-A total score (mean +/-SE) was similar between treatment groups (-8.54 [0.63] and -7.61 [0.64] for adjunctive risperidone and placebo, respectively; P = .265). Patients in each treatment group exhibited significant improvements from baseline in nearly all patient- and clinician-rated measures. A post-hoc analysis of PaRTS-A symptoms of moderate to severe severity at baseline suggested greater improvement with risperidone than placebo (P = .04). Headache, weight increase, and increased appetite were the most frequently reported adverse events in both groups. Conclusions: Residual GAD symptoms assessed by the PaRTS-A improved with either adjunctive risperidone or placebo. Alternative analyses or scoring approaches may improve the ability of the PaRTS-A to provide clinically meaningful information on patient-rated symptoms. Further exploration of the benefits of risperidone in patients with more severe GAD may be indicated.     

A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder

The selective 5HT₃ antagonist tropisetron was studied in 91 outpatients meeting DSM-III criteria for Generalized Anxiety Disorder. Following a placebo washout period of up to 1 week, one of three active treatments (tropisetron 0.5 mg, 5 mg, or 25 mg daily) or placebo was given for a further 3 weeks. After 7 days treatment termination rates due to inefficacy showed a statistically significant dose-related therapeutic effect of tropisetron. Similar effects were seen on the Hopkins Symptom Check List total score and the Global Impression Scale. The Hamilton Anxiety Scale showed a similar trend which, however, failed to reach statistical significance. At day 21 tropisetron showed significant dose-dependent effects on all anxiety-related outcome measures. The incidence of adverse events was low and the severity generally mild. Most frequent complaints were headache, nausea, constipation and nervousness. Laboratory tests and physical examination performed at baseline and study end showed no significant treatment effects.(Drs Braconnier, Combes Lepastier, Danic, Deyrieux, Fabiani, Lazartigues, Peyrouzet, Raikovic and Supino-Viterbo)