title: Multicenter collaborative panic disorder severity scale. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. Treatment of residual anxiety symptoms with adjunctive aripiprazole in depressed patients taking selective serotonin reuptake inhibitors. Components of variance and intraclass correlations for the design of community-based surveys and intervention studies: data from the Health Survey for England 1994. Olanzapine Augmentation in Treatment-Resistant Panic Disorder: A 12-Week, Fixed-Dose, Open-Label Trial Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: preliminary findings Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients Quetiapine as monotherapy for social anxiety disorder: A placebo-controlled study The Anxiolytic Effect of the Novel Antipsychotic Ziprasidone Compared With Diazepam in Subjects Anxious Before Dental Surgery Adjunctive risperidone in the treatment of generalized anxiety disorder: a double-blind, prospective, placebo-controlled, randomized trial. A Randomized, Double-Blind Study of Once-Daily Extended Release Quetiapine Fumarate (Quetiapine XR) Monotherapy in Patients With Generalized Anxiety Disorder Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome. Aripiprazole as augmentation treatment of refractory generalized anxiety disorder and panic disorder. An open-label trial of risperidone augmentation for refractory anxiety disorders. Olanzapine Augmentation of Fluoxetine for Refractory Generalized Anxiety Disorder: A Placebo Controlled Study Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. Preliminary experience with adjunctive quetiapine in patients receiving selective serotonin reuptake inhibitors Ziprasidone Treatment of Refractory Generalized Anxiety Disorder: A Placebo-Controlled, Double-Blind Study Efficacy of olanzapine in social anxiety disorder: a pilot study The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety.
abstract: OBJECTIVE To address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication , it is important to identify additional therapeutic strategies for the management of panic symptoms . This article describes a r and omized , rater-blind study comparing low-dose risperidone to st and ard-of-care paroxetine for the treatment of panic attacks . Methods Fifty six subjects with a history of panic attacks were r and omized to receive either risperidone or paroxetine .  The subjects were then followed for eight weeks . Outcome measures included the Panic Disorder Severity Scale ( PDSS ) , the Hamilton Anxiety Scale ( Ham-A ) , the Hamilton Depression Rating Scale ( Ham-D ) , the Sheehan Panic Anxiety Scale-Patient ( SPAS-P ) , and the Clinical Global Impression scale ( CGI ) . Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received . Statistically significant improvements in rating scale scores for both groups were identified for the PDSS , the Ham-A , the Ham-D , and the CGI . There was no difference between treatment groups in the improvement in scores on the measures PDSS , Ham-A , Ham-D , and CGI . Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine . Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks . Low-dose risperidone appears to be tolerated equally well as paroxetine . Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component . Trial Registration Clinical Trials.gov Identifier : The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) .  Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P<0.001 ) . Fewer patients receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P<0.001 ) and Q-LES-Q ( P<0.05 ) scores . AEs ( > 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis  . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine The efficacy and tolerability of extended-release quetiapine fumarate ( quetiapine XR ) once-daily monotherapy in generalized anxiety disorder ( GAD ) was assessed . This multicentre , double-blind , r and omized , placebo- and active-controlled , phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk ( 8-wk active treatment , 2-wk post-treatment drug-discontinuation ) study period ; 873 patients were r and omized to 50 mg or 150 mg quetiapine XR , 20 mg paroxetine , or placebo . Primary endpoint was change from r and omization at week 8 in Hamilton Rating Scale for Anxiety ( HAMA ) total score . At week 8 , all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo ; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR . Significant separation from placebo ( -2.90 ) in HAMA total score was observed at day 4 for 50 mg quetiapine XR ( -4.43 , p<0.001 ) and 150 mg quetiapine XR ( -3.86 , p<0.05 ) , but not for paroxetine ( -2.69 ) . Remission ( HAMA total score 7 ) rates at week 8 were significantly higher for 150 mg quetiapine XR ( 42.6 % , p<0.01 ) and paroxetine ( 38.8 % , p<0.05 ) vs. placebo ( 27.2 % ) . The most common adverse events ( AEs ) were dry mouth , somnolence , fatigue , dizziness , and headache , for quetiapine  XR , and nausea , headache , dizziness for paroxetine . A lower proportion of patients reported sexual dysfunction with quetiapine XR [ 0.9 % ( 50 mg ) , 1.8 % ( 150 mg ) ] than with placebo ( 2.3 % ) or paroxetine ( 7.4 % ) . The incidence of AEs potentially related to extrapyramidal symptoms was : quetiapine XR : 50 mg , 6.8 % , 150 mg , 5.0 % ; placebo , 1.8 % ; and paroxetine , 8.4 % . Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD , with symptom improvement seen as early as day 4 BACKGROUND Depression and anxiety are common disorders and have substantially overlapping symptom complexes . Not surprisingly , treatment approaches are similar for both conditions with the selective serotonin reuptake inhibitors ( SSRIs ) as the initial therapy of choice . However , after first line treatments have been deployed , residual symptoms are often problematic . Augmentation strategies to address these difficulties are an area of active investigation . This study assessed aripiprazole as adjunctive therapy to SSRIs for patients with persistent anxiety symptoms complicating a depression or anxiety disorder . METHODS Ten patients who had been receiving SSRIs for at least 6 weeks , but still had clinical ly significant anxiety symptoms , were enrolled in an open label , flexibly-dosed study of adjunctive aripiprazole . Clinical status was assessed with the Hamilton Anxiety Rating Scale ( HAM-A ) , Montgomery Asberg Rating Scale ( MADRS ) , and Sheehan Disability Scale ( SDS ) . RESULTS Eighty percent of the subjects had a greater than 50 % reduction of symptoms on these outcome measures by week 2 of therapy , and continued with further decrements in symptoms throughout the course of the study . CONCLUSIONS The results of this trial provide preliminary evidence that aripiprazole may be an effective adjunctive treatment in individuals on SSRIs with residual symptoms of anxiety or depression . More rigorous double-blind studies are warranted to confirm and eluci date the potential role of aripiprazole in these conditions The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed Rationale More data are needed to guide “ next step ” strategies for patients with generalized anxiety disorder ( GAD ) remaining symptomatic despite initial pharmacotherapy . Objective This study prospect ively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy . Material s and methods Adult out patients with GAD were recruited from 2004 to 2007 at two academic centers . Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day . Those remaining symptomatic ( Hamilton Anxiety Scale [ HAM-A ] ≥ 7 ) at week 10 were r and omized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day . Results For participants receiving paroxetine CR ( n = 50 ) , there was a significant reduction in HAM-A scores ( baseline mean ± SD = 22.4 ± 4.2 to endpoint mean ± SD = 11.2 ± 6.9 ; paired t = 12.1 , df = 49 , t < 0.0001 ) with 40 % ( n = 20 ) achieving remission . Counter to our hypothesis , we did not find significant benefit for quetiapine augmentation of continued paroxetine CR ( HAM-A reduction mean ± SD = 2.6 ± 5.8 points quetiapine , 0.3 ± 5.5 points placebo ; t = 0.98 , df = 20 , p = n.s . ) in the r and omized sample ( n = 22 ) with relatively minimal additional improvement overall in phase 2 . Conclusions Although conclusions are considered preliminary based on the relatively small sample size , our data do not support the addition of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospect i ve antidepressant pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve . We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic , aripiprazole . We report on patients with depression and anxiety disorders , including panic disorder , generalized anxiety disorder , social anxiety and post-traumatic stress disorder , who had an incomplete response to a variety of selective serotonin reuptake inhibitors ( SSRIs ) and who received augmentation with aripiprazole .  The primary outcome measure was the Clinical Global Impression of Improvement ( CGI-I ) . In the intent-to-treat analysis , the mean±SD CGI-S was 3.8±1.3 at endpoint . Fifty-nine percent of subjects received CGI-I ratings of 1 or 2 , ‘ much improved ’ or ‘ very much improved , ’ in terms of their depression and anxiety symptoms at the end of 12 weeks . Several patients showed an early ( weeks 1–5 ) , as well as sustained , response to augmentation with doses of aripiprazole between 15 and 30 mg/day . The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment . Because this is a retrospective case review , further prospect i ve studies are required to confirm these findings Social anxiety disorder ( SAD ) is one of the most common anxiety disorders . Reports have suggested an effect of the atypical antipsychotic quetiapine in anxiety disorders . Given these considerations , we conducted a controlled trial of quetiapine monotherapy in SAD . Fifteen patients were r and omized to quetiapine ( up to 400 mg/day ) or placebo for 8 weeks . The Brief Social Phobia Scale ( BSPS ) and the Clinical Global Impression of Improvement Scale ( CGI-I ) were the primary outcome measures , while the Social Phobia Inventory ( SPIN ) and the Sheehan Disability Inventory ( SDI ) were secondary measures . There was no significant difference on the BSPS score at endpoint between the quetiapine and placebo groups . There was a significant time effect but not a significant time x treatment group interaction , indicating that both the quetiapine and placebo patients did better over the course of the trial . 20 % of the quetiapine patients had a 50 % or greater drop in BSPS score at the end of the trial compared to baseline , while 0 % had such a drop in the placebo group . There was no significant difference in responders ( CGI-I score of 1 or 2 ) versus non-responder ( CGI-I score of 3 or more ) across the groups . However , 40 % of quetiapine patients and 0 % of the placebo patients showed much or very much improvement on the CGI-I. The Number Needed to Treat ( NNT ) to be a responder on the CGI-I was 3 . Significant time effects were noted for the SPIN and SDI , as well as a significant time x treatment effect in favor of quetiapine on the SPIN . Additionally , quetiapine showed a large effect size on the SPIN The novel atypical antipsychotic ziprasidone has a pharmacologic profile notable for potent agonism of serotonin (5-HT)1A receptors , antagonism at 5-HT1D receptors , and reuptake inhibition of norepinephrine . 5-HT1A receptor agonism , in particular , suggests anxiolytic activity , and ziprasidone has shown preliminary efficacy in treating the symptoms of anxiety associated with psychotic disorders . In this study , the anxiolytic efficacy of ziprasidone was evaluated in nonpsychotic subjects who were anxious before undergoing minor dental surgery . We compared a single oral dose of 20 mg ziprasidone ( N = 30 ) with that of 10 mg diazepam ( N = 30 ) and placebo ( N = 30 ) in a r and omized , parallel-group , double-blind study . The peak anxiolytic effect of ziprasidone compared with that of placebo was similar to that of diazepam but had a later onset . At 3 hours postdose , the anxiolytic effect of ziprasidone was significantly greater than that of placebo ( p < 0.05 ) and somewhat greater than that of diazepam . Diazepam showed a significantly greater anxiolytic effect than placebo at 1 hour ( p < 0.05 ) but not at 3 hours . The sedative effect of ziprasidone was never greater than that of placebo , whereas that of diazepam was significantly greater than that of placebo 1 to 1.5 hours postdose . Ziprasidone was generally well tolerated . Only one patient reported treatment-related adverse events ( nausea and vomiting ) and , unlike diazepam , ziprasidone did not cause reductions in blood pressure . Dystonia , extrapyramidal syndrome , akathisia , and postural hypotension were not seen with ziprasidone . Thus , ziprasidone may possess anxiolytic effects in addition to its antipsychotic properties 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 vali date d 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 r and omized  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 clinical ly meaningful information on patient-rated symptoms . Further exploration of the benefits of risperidone in patients with more severe GAD may be indicated This study evaluated once-daily , extended-release quetiapine fumarate ( quetiapine XR ) monotherapy in  generalized anxiety disorder ( GAD ) . This was a 10-week ( 8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase ) , double-blind , r and omized , placebo-controlled study ( D1448C00009 ) . Primary end point was change from r and omization at week 8 in Hamilton Anxiety Rating Scale ( HAM-A ) total score . Overall , 951 patients with GAD were r and omized  ( quetiapine XR : 50 mg/d , n = 234 ; 150 mg/d , n = 241 ; 300 mg/d , n = 241 ; placebo , n = 235 ) . At week 8 , HAM-A total scores significantly ( P < 0.001 ) improved versus placebo ( −11.10 ) with quetiapine XR 50 mg/d ( −13.31 ) and 150 mg/d ( −13.54 ) , but not 300 mg/d ( −11.87 ; P = 0.240 ) . At week 1 , HAM-A total scores significantly improved versus placebo ( −5.94 ) with quetiapine XR 50 mg/d ( −7.47 ; P < 0.01 ) , 150 mg/d ( −8.19 ; P < 0.001 ) , and 300 mg/d ( −7.23 ; P < 0.01 ) . Versus placebo at week 8 , quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic ( P < 0.01 and P < 0.001 , respectively ) and somatic ( P < 0.001 ; P < 0.01 , respectively ) cluster scores , HAM-A response ( ≥50 % total score reduction ; P < 0.05 ) , and Clinical Global Impression-Improvement categorical changes ( P < 0.05 ) . For quetiapine XR 150 mg/d , significant ( P < 0.05 ) improvements were seen for HAM-A remission ( total score , ≤7 ) and Clinical Global Impression-Severity of Illness scores . For quetiapine XR 300 mg/d , improvements in these secondary variables were not significantly different versus  placebo . Pittsburgh Sleep Quality Index global scores improved with all 3 doses ( quetiapine : XR 50 mg/d , −4.07 [ P < 0.05 ] ; 150 mg/d , −4.38 [ P < 0.05 ] ; 300 mg/d , −3.97 [ P < 0.05 ] , versus −3.31 with placebo ) . Adverse events ( > 10 % with quetiapine XR ) were dry mouth , somnolence , sedation , dizziness , headache , and fatigue .  Quetiapine XR ( 50/150 mg/d ) monotherapy was effective at week 8 in patients with GAD ; symptom improvement was seen at week 1 for all doses ( 50/150/300 mg/d ) . Safety and tolerability were consistent with the known profile of quetiapine BACKGROUND This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy ( CBGT ) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia . METHODS One hundred thirty-three patients from 2 sites received 12 weeks of CBGT , phenelzine therapy , pill placebo administration , or educational-supportive group therapy ( an attention-placebo treatment of equal credibility to CBGT ) . The " allegiance effect , " ie , the tendency for treatments to seem most efficacious in setting s of similar theoretical orientation and less efficacious in theoretically divergent setting s , was also examined by comparing responses to the treatment conditions at both sites : 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment . RESULTS After 12 weeks , phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition . However , response to phenelzine therapy was more evident after 6 weeks , and phenelzine therapy was also superior to CBGT after 12 weeks on some measures . There were few differences between sites , suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances . CONCLUSIONS After 12 weeks , both phenelzine therapy and CBGT were associated with marked positive response . Although phenelzine therapy was superior to CBGT on some measures , both were more efficacious than the control conditions . More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect INTRODUCTION Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent . More research examining pharmacotherapy augmentation strategies to improve outcomes is needed . METHODS In an 8-week , open-label , prospect i ve augmentation study , we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult out patients with generalized anxiety disorder ( n=13 ) or panic disorder ( n=10 ) who remained symptomatic despite treatment for at least 8 weeks with an adequate ( or maximally tolerated ) dose of typical pharmacotherapy . RESULTS Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores ( paired t=4.41 , df=22 , P<.001 ) in the intent-to-treat sample of 23 individuals . Three subjects ( 13 % ) discontinued due to sedation , chest discomfort , and restlessness , respectively . CONCLUSION These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy BACKGROUND There is a paucity of data to support " next-step " treatments for the many patients with anxiety disorders who remain symptomatic after initial pharmacotherapy . METHOD Thirty patients with a primary diagnosis of an anxiety disorder-panic disorder ( PD ) , social anxiety disorder ( SAD ) , or generalized anxiety disorder (GAD)-refractory to initial pharmacotherapy with an adequate ( or maximally tolerated ) antidepressant and /or benzodiazepine trial of at least 8 weeks ' duration prior to study initiation received open-label augmentation with  flexibly dosed risperidone for 8 weeks . Participants were diagnosed using the Structured Clinical Interview for DSM-IV . RESULTS Risperidone augmentation at a mean + /- SD dose of 1.12 + /- 0.68 mg/day ( range , 0.25 - 3.00 mg/day ) result ed in a significant reduction in anxiety symptoms across disorders as measured by the Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Anxiety ( HAM-A ) scores and for each disorder-specific primary outcome measure-the Panic Disorder Severity Scale , the Liebowitz Social Anxiety Scale , and HAM-A-in the intent-to-treat sample . Seventy percent ( 21/30 ) of participants completed the 8-week trial , with premature discontinuation due primarily to sedation and weight gain . CONCLUSIONS Although conclusions are limited by the open-label , relatively brief nature of this trial , our data suggest that augmentation with low-dose risperidone may be a useful option for patients with PD , SAD , or GAD refractory to adequate initial intervention with antidepressants and /or benzodiazepines . Longer-term , controlled safety and efficacy data are needed to underst and the place of risperidone augmentation in the algorithm of treatment options for refractory anxiety disorders BACKGROUND There has been little systematic study of " next-step " interventions for patients with generalized anxiety disorder ( GAD ) who remain symptomatic despite initial pharmacotherapy . We present one of the first r and omized controlled trials for refractory GAD , comprising double blind augmentation with olanzapine or placebo for patients remaining symptomatic on fluoxetine . METHODS Patients remaining symptomatic after 6 weeks of fluoxetine ( 20 mg/day ) were r and omized to 6 weeks of olanzapine ( mean dose 8.7 + /- 7.1 mg/day ) or placebo augmentation . RESULTS Twenty-four of 46 fluoxetine-treated patients were r and omized . Olanzapine result ed in a greater proportion of treatment responders based on a Clinical Global Impression-Severity Scale ( CGI-S ) end point score of 1 or 2 ( Fisher 's exact test [ FET ] p < .05 ) or a 50 % reduction in Hamilton Anxiety Scale ( HAMA-A ) score ( FET p < .05 ) . There were no other statistically significant differences for olanzapine compared with placebo augmentation in outcome measures , though rates of remission ( HAM-A < or= 7 ) on olanzapine were higher at the level of a trend ( FET , p = .1 ) . Average weight gain for completers was greater with olanzapine than placebo augmentation ( 11.0 + /- 5.1 vs. -0.7 + /- 2.4 pounds : t = 6.32 , p < .001 ) . CONCLUSIONS Olanzapine may have a salutary effect on anxiety for some GAD patients remaining symptomatic despite initial serotonin selective reuptake inhibitor ( SSRI ) therapy , but the emergence of significant weight gain represents an important clinical consideration 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 evidence d 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 r and omly 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 Treatment of depression and anxiety disorders with selective serotonin reuptake inhibitors ( SSRIs ) has been shown by numerous studies to be generally effective . Less well understood is how clinical ly to address the residual anxiety symptoms a significant minority of such patients treated with SSRIs continue to experience . We assessed quetiapine as adjunctive therapy to SSRIs for patients with anxiety symptoms complicating a depressive or anxiety disorder . Patients receiving a stable dosage of an SSRI for at least 6 weeks who also had persistent anxiety symptoms ( Hamilton Anxiety scale [ HAM‐A ] ≥16 ) , were enrolled in a 9‐week , open‐label , variable dose study . Changes in clinical status were assessed with the Hamilton Depression Rating Scale ( HAM‐D ) , HAM‐A , and State Anxiety Inventory ( SAI ) . Statistically and clinical ly significant reductions of ≥50 % in the HAM‐D and HAM‐A occurred by the second week of treatment in 10 of the 11 patients . These improvements continued throughout the study along with a significant improvement on the SAI scale . The most frequent side effects reported were mild dry mouth , constipation , and transient drowsiness with dose escalation . The results provide evidence that quetiapine may be an effective adjunctive treatment for recalcitrant anxiety symptoms in individuals treated with SSRIs for either anxiety or depressive disorders . Given the open‐label design of the trial , more rigorous studies are clearly indicated . Depression and Anxiety 19:121‐126 , 2004 . © 200 Wiley‐Liss , This 8-week , r and omized , double-blind , placebo-controlled , flexible-dose trial assessed the efficacy , safety , and tolerability of ziprasidone in adults with treatment-resistant generalized anxiety disorder ( GAD ) . Seventy-three subjects with treatment-resistant GAD were recruited , and 62 were r and omized to either ziprasidone or placebo treatment at a ratio of 2:1 using a flexible dosing strategy ( 20 - 80 mg daily ) . R and omization was stratified into 2 subtypes of patients , those in whom the study drug was used as augmentation and those who have stopped their ineffective medications before entering the present trial ( nonaugmented group ) . The subjects ' clinical status was monitored weekly throughout the course of the study and included the Hamilton Anxiety Scale ( primary outcome measure ) , the Clinical Global Impression Improvement and Severity of Illness scales , the Hamilton Depression Scale , the Sheehan Disability Scale , the Hospital Anxiety and Depression Scale , and the Abnormal Involuntary Movements Scale .  Sixty-two patients were r and omized to ziprasidone ( n = 41 ) or placebo ( n = 21 ) . The dropout rate was 24 % , consisting of 2 placebo patients and 13 ziprasidone patients . There was no statistically significant difference in the Hamilton Anxiety Scale score reduction between the drug and placebo groups . However , statistical trends were observed for an augmentation- study medication interaction effect , with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group . This study provides pilot data for an augmentation- study medication interaction effect with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group . Based on the data obtained in this trial and the subsequent power analyses , a future double-blind placebo-controlled trial should include at least 150 treatment-resistant GAD nonaugmented patients r and omized to ziprasidone and placebo in a 1:1 ratio Based on evidence suggesting anxiolytic properties of the atypical antipsychotic olanzapine , this study was conducted to evaluate whether olanzapine may be efficacious in treating  social anxiety disorder ( SAD ) . This study was an 8-week , double-blind , placebo-controlled evaluation of olanzapine as monotherapy in which 12 patients with the DSM-IV diagnosis of SAD were r and omized to either olanzapine ( n= 7 ) or placebo ( n= 5 ) . An initial dose of 5 mg/day was titrated to a maximum of 20 mg/day . Baseline to endpoint scores from the Brief Social Phobia Scale ( BSPS ) , Social Phobia Inventory ( SPIN ) , Liebowitz Social Anxiety Scale and Sheehan Disability Scale , as well as Clinical Global Impression-Improvement ratings , were compared for olanzapine versus placebo .  Seven subjects completed all 8 weeks of the study , four in the olanzapine group and three in the placebo group . In the intent-to-treat analysis , olanzapine yielded greater improvement than placebo on the primary measures : BSPS ( p= 0.02 ) and SPIN ( p= 0.01 ) . Both treatments were well tolerated , although the olanzapine group had more drowsiness and dry mouth .  Olanzapine and placebo were both associated with negligible weight gain .  Olanzapine was superior to placebo on the primary outcome measures in this preliminary study of SAD . Additional studies of olanzapine as a treatment for SAD are warranted To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results BACKGROUND The treatment of bipolar disorder is often complicated by the presence of a co-occuring anxiety disorder . Although second generation antipsychotics are being used with increasing frequency in bipolar patients , their anxiolytic effects have not been well studied in this population . METHODS The anxiolytic effect of risperidone 0.5 - 4 mg/day was tested in an 8-week , double-blind , placebo-controlled , r and omized clinical trial in 111 patients with bipolar disorder and a co-occuring panic disorder or generalized anxiety disorder ( GAD ) . The primary outcome measure was the Clinician Global Improvement-21 Anxiety scale ( CGI-21 Anxiety ) . Secondary measures included the Hamilton Anxiety Scale ( HAM-A ) and the Sheehan Panic Disorder Scale . RESULTS On the last-observation-carried forward analysis of repeated measures analysis of variance ( ANOVA ) , risperidone was not more effective than placebo for the CGI-21 Anxiety score or the other anxiety outcome measures .  Risperidone was well tolerated , with only two patients withdrawing because of adverse events . LIMITATIONS The  risperidone treated group had more patients with mixed states and lifetime panic disorder at r and omization than the placebo group . The study was limited to 8 weeks and to individuals with bipolar and comorbid panic disorder or GAD . The results may not be applicable to risperidone as an add-on treatment to mood stabilizers , or to bipolar disorder comorbid with anxiety disorders other than panic disorder or GAD . CONCLUSIONS Risperidone monotherapy was not an effective anxiolytic for bipolar patients with comorbid panic disorder or GAD in doses of 0.5 - 4 mg/day over 8 weeks of treatment . The efficacy of other second generation antipsychotics and mood stabilizers on anxiety in patients with bipolar disorder and a co-occuring anxiety disorder should be investigated in double-blind , placebo-controlled studies
target: Monotherapy with quetiapine seems to be efficacious in reducing symptoms of generalised anxiety disorder and this effect may be similar to that of antidepressants .
background: BACKGROUND Anxiety disorders are common and disabling conditions , with a lifetime prevalence of 17 % in the general population .
  Due to high rates of treatment resistance , there is interest in new pharmacological treatment options such as second-generation antipsychotics .
  OBJECTIVES To evaluate the efficacy and tolerability of second-generation antipsychotics as monotherapy or adjunctive treatment for people with anxiety disorders .