The diagnosis and treatment of generalized anxiety disorder. Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia. Benzodiazepine discontinuation among adults with GAD: A randomized trial of cognitive-behavioral therapy. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder Protocol for a randomised controlled trial investigating the effectiveness of an online e-health application compared to attention placebo or sertraline in the treatment of generalised anxiety disorder Pharmacotherapy of anxiety. Paroxetine efficacy in the treatment of generalized anxiety disorder Psychopharmacotherapy of somatoform disorders: effects of opipramol on symptoms of somatization, anxiety, and depression. Efficacy and Safety of Lesopitron in Outpatients with Generalized Anxiety Disorder Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. Efficacy of an acceptance-based behavior therapy for generalized anxiety disorder: evaluation in a randomized controlled trial. Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety. Efficacy of a cognitive-behavioral treatment for generalized anxiety disorder: evaluation in a controlled clinical trial. Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care
BACKGROUND Generalized anxiety disorder  ( GAD ) is a common and serious disease with a lifetime prevalence of 4.3 % to 5.9 % . It is underdiagnosed in primary care . METHODS Recommendations on the treatment of GAD are given on the basis of all available findings from pertinent r and omized trials , retrieved by a selective search of the literature . RESULTS Among psychotherapeutic techniques , various kinds of cognitive behavioral therapy ( CBT ) have been found useful in controlled trials . The drugs of first choice include selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-norepinephine reuptake inhibitors ( SNRIs ) , and the calcium-channel modulator pregabalin . Tricyclic antidepressants are also effective but have more adverse effects than SSRIs . Although benzodiazepines are effective anxiolytic agents for short-term use , they should not be given over the long term because of the danger of addiction . Buspirone , an azapirone , was found to be effective in a small number of trials , but the findings across trials are inconsistent . The response rate of GAD to CBT in published studies lies between 47 % and 75 % , while its response rate to drug treatment lies between 44 % and 81 % . CONCLUSION The treatment of GAD with CBT and drugs is evidence -based and has a good chance of improving the manifestations of the disorder The past decade has brought major new developments in the psychopharmacologic management of generalized anxiety disorder and social phobia . We examined medication-prescribing patterns for the treatment of these anxiety disorders for 12 years to assess changes in patients ' anti-anxiety psychotropic medication usage during that period of evolving practice guidelines . We examined psychotropic medication use in 305 patients with generalized anxiety disorder and 232 with social phobia enrolled in the Harvard/Brown Anxiety Disorders Research Project ( HARP ) , a prospect i ve , longitudinal study of anxiety disorders .  Psychotropic treatment patterns seem to have remained relatively stable over 12 years with benzodiazepines the medications most commonly used for both generalized anxiety disorder and social phobia . Comparatively , selective serotonin reuptake inhibitor ( SSRI ) and venlafaxine usage as st and -alone medications for these disorders remained low throughout the follow-up period . At the 12-year follow-up , 24 % of patients with generalized anxiety disorder and 30 % of patients with social phobia were utilizing neither an  SSRI/selective norepinephrine reuptake inhibitor ( SNRI ) nor a benzodiazepine . Treatment recommendations for use of SSRIs and venlafaxine in the management of generalized anxiety disorder and social phobia initially promulgated in 1998 had a modest impact on changes in psychopharmacologic practice 4 - 5 years later . Difficulties in the implementation of treatment guidelines are discussed This study evaluated the specific effectiveness of cognitive-behavior therapy ( CBT ) combined with medication tapering for benzodiazepine discontinuation among generalized anxiety disorder ( GAD ) patients by using a nonspecific therapy control group . Sixty-one patients who had used benzodiazepines for more than 12 months were r and omly assigned to the experimental conditions . Nearly 75 % of patients in the CBT condition completely ceased benzodiazepine intake , as compared with 37 % in the control condition . Results of the 3- , 6- , and 12-month follow-ups confirmed the maintenance of complete cessation . Discontinuation rates remained twice as high in the CBT condition . The number of patients who no longer met GAD criteria was also greater in the CBT condition . The addition of specific CBT components thus seemed to facilitate benzodiazepine tapering among patients with GAD In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy Antidepressant drugs are the preferred choice for the treatment of generalized anxiety disorder ( GAD ) . However , the choice of pharmacotherapy is determined on a trial- and -error basis , as the underlying mechanisms of treatment response are unknown . We examined whether the COMT gene , which has been known to play a role in antidepressant treatment response in major depressive disorder ( MDD ) , has a pharmacogenetic effect in antidepressant treatment response in GAD . In our study , 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes were obtained for the COMT functional variant rs4680 ( Val158Met ) for all patients ; however , pharmacogenetic analysis was only conducted for the European American population ( n=112 ) . We found no significant association between our primary Hamilton Anxiety Scale outcome measure and rs4680 . However , we did find a nominally significant allelic association between this variant and a secondary treatment outcome measure ( CGI-I ) in our European American population ( n=112 ) . Furthermore , we show a slight dominant effect of the A-allele with the CGI-I measure in the European American population indicating a possible pharmacogenetic role of rs4680 in antidepressant treatment outcome in GAD . Further studies in a larger population are needed to confirm this effect Background Generalised anxiety disorder ( GAD ) is a high prevalence , chronic psychiatric disorder which commonly presents early in the lifespan . Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder ( PTSD ) , panic disorder , social phobia and depression . However , to date , there is little evidence for the effectiveness of e-health applications in adult GAD . There are no studies which have directly compared e-health applications with recognised evidence -based medication . This study aims to determine the effectiveness of a  web-based program for treating GAD relative to sertraline and attention placebo . Methods / Design 120 community-dwelling participants , aged 18 - 30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll . They will be r and omly allocated to one of three conditions : ( i ) an online treatment program for GAD , E-couch ( ii ) pharmacological treatment with a selective serotonin re-uptake inhibitor ( SSRI ) , sertraline ( a fixed-flexible dose of 25 - 100 mg/day ) or ( iii ) an attention control placebo , HealthWatch . The treatment program will be completed over a 10 week period with a 12 month follow-up . Discussion As of February 2010 , there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults . Similarly to date , this will be the first trial to compare an e-health intervention with a pharmacological treatment . Trial Registration Current Controlled Trials IS RCT The pharmacological treatment of anxiety has a long and chequered history , and recent years have seen a rich development in the options available to prescribers . Most of the currently used anxiolytic agents act via monoaminergic ( chiefly serotonin ) or amino acid ( GABA or glutamate ) neurotransmitters , and this chapter describes the pharmacology of the major drug groups . Clinical applications are discussed with respect to the five major anxiety disorders , as well as simple phobia and depression with concomitant anxiety . Prospect i ve future developments in the field are considered Recently , there has been a renewed interest in alternatives to the benzodiazepines for the treatment of  generalized anxiety disorder ( GAD ) . The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2′‐chlordesmethyldiazepam in 81 patients with a DSM‐IV diagnosis of GAD . Approximately two‐thirds of the patients who completed the study improved greatly or moderately on all three active drugs . During the first 2 weeks of treatment , 2′‐chlordesmethyldiazepam treatment result ed in the greatest improvement in anxiety ratings . Both paroxetine and imipramine treatment result ed in more improvement than 2′‐chlordesmethyldiazepam by the fourth week of treatment . Paroxetine and imipramine affect predominantly psychic symptoms , whereas 2′‐chlordesmethyldiazepam affects predominantly somatic symptoms . Our results suggest that paroxetine is effective for the treatment of GAD BACKGROUND The psychopharmacotherapy of somatoform disorders ( SD ; ICD-10 : F45 ) has been less frequently investigated and is not as well established as in other ( neurotic ) disorders of ICD-10 section F4 , i.e. generalized anxiety disorder ( GAD ; ICD-10 : F41.1 ) . The atypical compound opipramol is very often used to treat SD and GAD in clinical practice in Germany . However , state-of-the-art controlled clinical trials have not yet been performed . OBJECTIVES Two clinical trials were performed with the aim of confirming the efficacy and tolerability of opipramol in SD and GAD . METHODS Both trials were performed as r and omized , double-blind , placebo-controlled , multicenter studies . While the GAD trial was a three-arm study with opipramol ( 200 mg/day ) vs. placebo and alprazolam ( 2 mg/day ) for 28 days , the SD trial was a placebo-controlled two-arm study with a treatment duration of 42 days . Each group consisted of about 100 patients . RESULTS Significant differences ( alpha = 0.05 ) were found for the primary efficacy criteria ( HAMA total score in GAD , HAMA somatic subscore in SD ) and most of the secondary criteria in favor of the active drug therapies . Considerable differences between the psychopathology of SD and GAD were detected . CONCLUSION The well-tolerated anxiolytic opipramol is the first psychotropic drug with proven efficacy in somatoform disorders with effects on symptoms of somatization , anxiety , and depression . The compound is also effective and safe in GAD OBJECTIVE : To compare the relative efficacy and safety of lesopitron 40–80 mg/d versus lorazepam 2–4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder ( GAD ) . DESIGN : Six-week , r and omized , double-blind , parallel , placebo and lorazepam-controlled , Phase II , single-center , outpatient study . SETTING : Outpatient clinic . PATIENTS : One hundred sixty-one patients with GAD were r and omized in the main study ; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup . METHODS : After a one-week placebo lead-in , patients were r and omized to receive placebo , lesopitron , or lorazepam twice daily for six weeks , followed by a one-week taper period . Efficacy was assessed using the Hamilton Rating Scale for Anxiety ( HAM-A ) and the Clinical Global Impressions scale . Safety was assessed through physical examinations , monitoring of vital signs , 12-lead electrocardiograms , laboratory analyses , and adverse event monitoring . RESULTS : An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen , with mean changes of 3.4 ( 95 % CI 2.0 to 4.8 ) , 6.1 ( 95 % CI 4.1 to 8.1 ) , and 6.1 ( 95 % CI 4.6 to 7.6 ) for the placebo , lesopitron , and lorazepam groups , respectively ( omnibus p = 0.044 , uncorrected ) . Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted . Future trials could be stratified on the basis of referral status ( symptomatic volunteer vs. clinical patient with preexisting illness ) or previous exposure to anxiolytics , and use a fixed-dose rather than flexible-fixed-dose design . CONCLUSIONS : The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history . Although the overall study analysis was equivocal , for the approximately 40 % of patients with recurrent anxiety disorder , beneficial effects for both lesopitron and lorazepam are suggested 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 Generalized anxiety disorder ( GAD ) is a chronic anxiety disorder , associated with comorbidity and impairment in quality of life , for which improved psychosocial treatments are needed . GAD is also associated with reactivity to and avoidance of internal experiences . The current study examined the efficacy of an acceptance-based behavioral therapy aim ed at increasing acceptance of internal experiences and encouraging action in valued domains for GAD . Clients were r and omly assigned to immediate ( n = 15 ) or delayed ( n = 16 ) treatment .  Acceptance-based behavior therapy led to statistically significant reductions in clinician-rated and self-reported GAD symptoms that were maintained at 3- and 9-month follow-up assessment s ; significant reductions in depressive symptoms were also observed . At posttreatment assessment 78 % of treated participants no longer met criteria for GAD and 77 % achieved high end-state functioning ; these proportions stayed constant or increased over time . As predicted , treatment was associated with decreases in experiential avoidance and increases in mindfulness 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 Recent advances in the underst and ing of worry have led to the development of treatments for generalized anxiety disorder ( GAD ) . The present study tested a GAD treatment that targeted intolerance of uncertainty , erroneous beliefs about worry , poor problem orientation , and cognitive avoidance . Twenty-six primary GAD patients were r and omly allocated to a treatment condition ( n = 14 ) or a delayed treatment control condition ( n = 12 ) . Self-report , clinician , and significant other ratings assessed GAD and associated symptoms . The results show that the treatment led to statistically and clinical ly significant change at posttest and that gains were maintained at 6- and 12-month follow-ups . Furthermore , 20 of 26 participants ( 77 % ) no longer met GAD diagnostic criteria following treatment . With regard to the treatment 's underlying model , the results show that intolerance of uncertainty significantly decreased over treatment and that gains were maintained at both follow-ups . Although nonspecific factors were not significant predictors of treatment outcome , their role in the treatment of GAD requires further investigation OBJECTIVE Recently , pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available . The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines . METHOD A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project , a prospect i ve longitudinal study of anxiety disorders . These patients were interviewed over the course of 10 years to examine their use of psychotropic medications . RESULTS Despite efforts aim ed at increasing the use of selective serotonin reuptake inhibitors ( SSRIs ) in patients with panic disorder ( e.g. , APA 's practice guideline for panic disorder , Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder ) , only a modest increase in their use was found . Treatment patterns for psychotropic drugs  appear to have remained stable over the past decade , with benzodiazepines being the most commonly used medication for panic disorder . In comparison , SSRI use throughout the follow-up period has remained low . Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine , nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly . CONCLUSIONS These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed . Factors potentially associated with promoting and ignoring treatment recommendations are discussed Abstract Objective . Anxiety disorders are frequently under-diagnosed conditions in primary care , although they can be managed effectively by general practitioners . Methods . This paper is a short and practical summary of the World Federation of Biological Psychiatry ( WFSBP ) guidelines for the pharmacological treatment of anxiety disorders , obsessive – compulsive disorder ( OCD ) and posttraumatic stress disorder ( PTSD ) for the treatment in primary care . The recommendations were developed by a task force of 30 international experts in the field and are based on r and omized controlled studies . Results . First-line pharmacological treatments for these disorders are  selective serotonin reuptake inhibitors  ( for all disorders ) ,  serotonin-norepinephrine reuptake inhibitors  ( for some ) and  pregabalin  ( for generalized anxiety disorder only ) . A combination of  medication and cognitive behavior/exposure therapy  was shown to be a clinical ly desired treatment strategy . Conclusions . This short version of an evidence -based guideline may improve treatment of anxiety disorders , OCD , and PTSD in primary care
Dropout rates did not differ between antidepressants .
The latter study showed very promising results of  sertraline  in children and adolescents with GAD , which warrants its replication in larger sample s. REVIEW ER 'S CONCLUSIONS The available evidence suggests that antidepressants are superior to placebo in treating GAD .
There is also evidence from placebo-controlled trials suggesting that these drugs are well tolerated by GAD patients .
Further trials of antidepressants for GAD will help to demonstrate which antidepressants should be used for which patients
BACKGROUND Pharmacological treatments have been successfully used to treat  Generalized Anxiety Disorder ( GAD ) .
The mainstay for the pharmacological treatment of GAD in past decades has been the use of benzodiazepine and non benzodiazepine anxiolytics .
Data emerging over the last two decades have shown that antidepressants may be equally effective to anxiolytics for treating GAD .
The use of antidepressants for treating GAD may be advantageous , due to the fact that GAD presents a high co morbidity ratio with major depressive disorder ( 62 % ) and dysthymia ( 37 % ) .
OBJECTIVES To assess the efficacy and acceptability of antidepressants for treating generalized anxiety disorder .