title: Neurotic illness and its response to anxiolytic and antidepressant treatment. Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Quality of life and psychiatric morbidity in panic disorder and generalized anxiety disorder. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. Phenomenology and course of generalised anxiety disorder. The relationships between clinical response, psychophysiological variables and plasma levels of amitriptyline and diazepam in neurotic outpatients Paroxetine efficacy in the treatment of generalized anxiety disorder Imipramine and buspirone in treatment of patients with generalized anxiety disorder who are discontinuing long-term benzodiazepine therapy. Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial. Imipramine and chlordiazepoxide in depressive and anxiety disorders. I. Efficacy in depressed outpatients.
abstract: Two hundred and forty neurotic out- patients were allocated to no diagnostic category but were rated in terms of observer and self ratings of both depression and anxiety at weekly intervals during a 4-week trial of amitriptyline , diazepam , amitriptyline and diazepam , and placebo . The sample could not be divided into anxious and depressed groups on the basis of the clinical picture . The outcome tended to be good irrespective of medication but the significant drug effects found were due to amitriptyline and concerned measures of anxiety as well as depression . It is concluded that a distinction between anxiety and depression in neurotic out- patients is of no practical value with regard to drug treatment OBJECTIVE This study evaluated the efficacy and safety of fixed doses of once-daily extended-release ( XR ) venlafaxine in out patients with generalized anxiety disorder without concomitant major depressive disorder . METHOD Adult out patients with generalized anxiety disorder but not major depressive disorder with total scores of 18 or higher on the Hamilton Rating Scale for Anxiety and scores of 2 or higher on its anxious mood and tension factors were eligible . Patients were r and omly assigned to receive placebo or venlafaxine XR ( 75 , 150 , or 225 mg/day ) for 8 weeks . Primary efficacy variables were final total and psychic anxiety factor scores on the Hamilton anxiety scale and final severity and global improvement item scores on the Clinical Global Impression ( CGI ) scale . RESULTS Of the 377 patients entering the study , 370 were included in a safety analysis and 349 in an efficacy analysis .  Adjusted mean scores at 8 weeks ( last-observation-carried-forward analysis ) were significantly lower for one or more of the venlafaxine XR groups in four of four primary and three of four secondary outcome measures than for the placebo group . These included a change of 1.7 ( versus 1.3 ) from baseline on CGI severity item scores and a final score of 2.2 ( versus 2.6 ) on the CGI global improvement item . All doses of venlafaxine XR were well tolerated . CONCLUSIONS Venlafaxine XR is an effective and well-tolerated option for the short-term treatment of generalized anxiety disorder in out patients without major depressive disorder OBJECTIVE This report examines the impact of panic disorder and /or generalized anxiety disorder on quality of life and the implication s of these findings on nosological categories . METHOD A total of 357 subjects with a current episode of panic disorder and /or generalized anxiety disorder were diagnosed according to DSM-III-R criteria , using structured clinical interviews , as part of a prospect i ve , naturalistic , longitudinal , multicenter study of a clinical population with anxiety disorders . RESULTS There was a high degree of coexistence of anxiety disorders and major depressive disorder . Subjects with generalized anxiety disorder almost universally had other disorders , were the most likely to have at least one other anxiety disorder or major depressive disorder at intake , had the earliest age at onset , and had the worst emotional health rating . Subjects with panic disorder without agoraphobia had the most likelihood of a history of alcohol abuse . Nine percent of the subjects had a history of suicide attempts or gestures . CONCLUSIONS The subjects showed significant impairment in quality of life . The highly frequent coexistence of other anxiety disorders with generalized anxiety disorder and the overall lack of differences on many quality of life measures raise questions of nosology , particularly for generalized anxiety disorder BACKGROUND The objective of this r and omized , double-blind study was to compare the efficacy and safety of venlafaxine extended release ( XR ) and buspirone in out patients with generalized anxiety disorder ( GAD ) but without concomitant major depressive disorder . METHOD Male and female out patients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety ( HAM-A ) were r and omly assigned to treatment with either venlafaxine XR ( 75 or 150 mg/day ) , buspirone ( 30 mg/day in 3 divided doses ) , or placebo for 8 weeks . The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale ( CGI ) scores . Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale ( HAD ) . RESULTS The efficacy analysis included 365 patients and the safety analysis , 405 . At week 8 , adjusted mean HAM-A psychic anxiety , anxious mood , and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients . On the HAD anxiety subscale , venlafaxine XR , 75 or 150 mg/day , was significantly more efficacious than placebo at all time points except weeks 1 ( both dosages ) and 2 ( 150-mg/day dosage only ) and significantly more efficacious than buspirone at all time points except week 1 . On the CGI-Improvement scale , scores for venlafaxine XR ( both dosages ) and buspirone were numerically superior to those for placebo at all time points , and statistical significance was observed at weeks 3 , 4 , 6 , and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone . The adverse events were not essentially different between treatment groups . CONCLUSION Venlafaxine XR is an effective , safe , and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder . This agent was significantly superior to buspirone on the HAD anxiety subscale . Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response BACKGROUND The diagnostic category of generalised anxiety disorder ( GAD ) was originally intended to describe residual anxiety states . Over the years clinical criteria have been refined in an attempt to describe a unique diagnostic entity . Given these changes , little is known about the clinical course of this newly defined disorder . This study investigates the longitudinal course , including remission and relapse rates , for patients with DSM-III-R defined GAD . METHOD Analysis of the 164 patients with GAD participating in the Harvard Anxiety Research Program . Patients were assessed with a structured clinical interview at intake and re-examined at six month intervals for two years and then annually for one to two years .  Psychiatric Status Ratings were assigned at each interview point . Kaplan-Meier curves were constructed to assess likelihood of remission . RESULTS Comorbidity was high , with panic disorder and social phobia as the most frequently found comorbid disorders . The likelihood of remission was 0.15 after one year and 0.25 after two years . The probability of becoming asymptomatic from all psychiatric symptoms was only 0.08 . CONCLUSIONS This prospect i ve study confirms the chronicity associated with GAD and extends this finding to define the one and two year remission rates for the disorder . Likelihood of remission for GAD and any other comorbid condition after one year was half the annual remission rate for GAD alone In a 4 week study of the response of neurotic out patients to treatment with amitriptyline , diazepam , amitriptyline and diazepam , or placebo , clinical and psychophysiological variables and plasma levels of the drug were assessed . Clinical improvements were substantial in all treatment groups but clear relationships between clinical change , psychophysiological change and plasma levels of the drugs were not established . There was no relationship between plasma levels of the drugs and cigarette smoking . It is concluded that neither plasma levels of amitriptyline and diazepam nor change in skin conductance responsivity offer a useful guide to clinical response to drug treatment 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 OBJECTIVE Patients with generalized anxiety disorder ( N=107 ) who had been long-term benzodiazepine users ( average duration of use=8.5 years ) were enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine ( 180 mg/day ) and buspirone ( 38 mg/day ) compared to placebo in facilitating benzodiazepine discontinuation . METHOD After a benzodiazepine stabilization period taking either diazepam , lorazepam , or alprazolam , patients were treated for 4 weeks with imipramine , buspirone , or placebo under double-blind conditions while benzodiazepine intake was kept stable ( treatment phase ) . Patients then entered a 4 - 6 week benzodiazepine taper and a 5-week posttaper phase with imipramine , buspirone , and placebo treatment being continued until 3 weeks into the posttaper phase , at which time all patients were switched to placebo for 2 weeks .  Benzodiazepine plasma levels were assayed weekly . Benzodiazepine-free status was assessed 3 and 12 months posttaper . RESULTS Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts . The success rate of the taper in this study was significantly higher for patients who received imipramine ( 82.6 % ) , and nonsignificantly higher for patients who received buspirone ( 67.9 % ) , than for patients who received placebo ( 37.5 % ) . The imipramine effect remained highly significant even after the analysis adjusted for three other independent predictors of taper success : benzodiazepine dose , level of anxious symptoms at baseline , and duration of benzodiazepine therapy . CONCLUSIONS Management of benzodiazepine discontinuation can be facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper . Daily benzodiazepine dose , severity of baseline symptoms of anxiety and depression , and duration of benzodiazepine use were additional significant predictors of successful taper outcome OBJECTIVE The current study examines whether antidepressants , contrary to current thinking , are safe and effective treatments for generalized anxiety disorder ( GAD ) not complicated by depression or panic disorder . DESIGN R and omized , double-blind , placebo-controlled , flexible-dose , 8-week treatment study comparing imipramine hydrochloride ( mean maximum daily dose , 143 mg ) , trazodone hydrochloride ( 255 mg ) , and diazepam ( 26 mg ) . PATIENTS Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded , and who had a Hamilton Anxiety Scale total score of at least 18 . SETTING Seventy-five percent of patients were treated in family practice setting s in the community , with the remainder treated in psychiatric practice s , either academic or private . RESULTS Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment , with somatic symptoms being most responsive . From week 3 through week 8 trazodone achieved comparable , and imipramine somewhat better , anxiolytic efficacy when compared with diazepam , with psychic symptoms of tension , apprehension , and worry being more responsive to the antidepressants . Among completers , moderate to marked improvement was reported by 73 % of patients treated with imipramine , 69 % of patients treated with trazodone , 66 % of patients treated with diazepam , but only 47 % of patients treated with placebo . Overall , patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients , but attention rates were the same across all treatments . CONCLUSIONS The results of the study need replication , but suggest a potentially important role for antidepressants , particularly imipramine , in patients suffering from GAD BACKGROUND The objective of this r and omized , double-blind , placebo-controlled study was to investigate the efficacy and safety of paroxetine in out patients with generalized anxiety disorder ( GAD ) .  METHOD Male and female out patients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety ( HAM-A ) were r and omly assigned to treatment with paroxetine ( 20 - 50 mg/day ) or placebo for 8 weeks . The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension , the anxiety subscale of the Hospital Anxiety and Depression Scale , and the Sheehan Disability Scale ( SDS ) . The proportions of patients fulfilling response and remission criteria at week 8 were also determined . RESULTS The intent-to-treat population included 324 patients . At week 8 , compared with the placebo group ( N = 163 ) , the paroxetine group ( N = 161 ) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables . On the HAM-A anxious mood item , which encompasses the cardinal symptoms of GAD , significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain " social life " as early as week 4 for paroxetine compared with placebo . In both the last-observation-carried-forward and completer data sets , significantly greater proportions of paroxetine-treated patients achieved response or remission by week 8 . Treatment with paroxetine was well tolerated , and the number and type of adverse events recorded in the paroxetine group correspond to the known safety profile of this medication . CONCLUSION Paroxetine in doses of 20 to 50 mg once daily is effective in the treatment of patients with GAD . Improvement of core symptoms of GAD occurs early and is associated with significant reduction in disability after only 8 weeks of treatment OBJECTIVE The study compared the safety and efficacy of sertraline , a selective serotonin reuptake inhibitor , and placebo in the treatment of generalized anxiety disorder in children and adolescents . METHOD The study subjects were 22 children and adolescents age 5 - 17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children-Revised and who had a Hamilton Anxiety Rating Scale score > or = 16 . The patients underwent a 2 - 3-week pre study evaluation period , followed by a 9-week double-blind treatment phase in which they were r and omly assigned in blocks of four to receive either sertraline or pill placebo . The maximum dose of sertraline was 50 mg/day . Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale . RESULTS The Hamilton anxiety scale total score , psychic factor , and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4 . Self-report measures reflected these results at the end of treatment . CONCLUSIONS The results of this double-blind , placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents BACKGROUND Generalised anxiety disorder ( GAD ) has received less study than other anxiety disorders , particularly its long-term treatment . AIMS To assess the efficacy and safety of venlafaxine extended release ( ER ) in patients with GAD . METHOD A total of 541 out- patients , 18 - 86 years old , were recruited to this 24-week , placebo-controlled , double-blind study of three fixed doses ( 37.5 , 75 and 150 mg/day ) of venlafaxine ER . RESULTS All doses of venlafaxine ER showed efficacy superior to placebo , apparent from week 2 , that was sustained throughout the 24-week study for the two higher doses . The discontinuation rate did not differ significantly among the treatment groups . CONCLUSIONS Venlafaxine ER is an effective and safe treatment for GAD for up to 6 months CONTEXT Generalized anxiety disorder ( GAD ) is a chronic disorder that is associated with debilitating psychic and somatic symptoms . Venlafaxine extended-release ( XR ) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder ( MDD ) , but long-term data are needed to establish whether this agent confers persistent benefits . OBJECTIVE To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in out patients with GAD without associated MDD . DESIGN Six-month , r and omized , double-blind , placebo-controlled , parallel-group trial conducted May 1996 to October 1997 . SETTING Fourteen outpatient clinics and private psychiatric practice s in the United States . PARTICIPANTS A total of 251 out patients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for GAD , had sufficient symptoms to require treatment , and did not have coexisting MDD . INTERVENTIONS Participants were r and omly assigned to receive either placebo ( n=127 ) or venlafaxine XR ( 75 , 150 , or 225 mg/d , as required to control symptoms ; n=124 ) for 28 weeks . MAIN OUTCOME MEASURES Changes from baseline in the Hamilton Rating Scale for Anxiety ( HAM-A ) total score , the HAM-A psychic anxiety factor score , and the Clinical Global Impressions ( CGI ) scale Severity of Illness and Global Improvement scores , compared by intervention group . RESULTS During weeks 6 through 28 , response rates in the venlafaxine XR group were 69 % or higher compared with rates of 42 % to 46 % in the placebo group ( P<.001 ) . By an evaluable-patient analysis , venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures , including the HAM-A total ( P<.001 ) , the HAM-A psychic anxiety factor ( P<.001 ) , and the CGI scale scores ( P<.001 ) . Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A , venlafaxine XR -13.4 , placebo -8.7 ( P<.001 ) ; for HAM-A psychic anxiety score , venlafaxine XR -7.4 , placebo -4.2 ( P<.001 ) ; and for CGI-Improvement , venlafaxine XR 2.2 , placebo 3.0 ( P<.001 ) . The most common treatment-emergent adverse event was nausea , followed by somnolence and dry mouth . CONCLUSIONS This study is the first placebo-controlled demonstration of the long-term efficacy of any drug class in treating out patients with DSM-IV-diagnosed GAD .  Venlafaxine XR is an effective , rapidly acting , safe , once-daily agent for both the short- and long-term treatment of anxiety and may provide an important alternative to currently available anxiolytics . JAMA . 2000 We r and omly assigned 425 out patients , independently classified as primarily depressed by two trained psychiatrists , to double-blind treatment with Imipramine hydrochloride , chlordiazepoxide hydrochloride , or placebo .  Those patients who remained at least moderately depressed ( following a two-week placebo washout period ) were treated for an additional eight weeks . An endpoint analysis of 387 patients who completed two or more weeks of medication disclosed early therapeutic advantages of chlordiazepoxide . By week 4 of treatment , however , imipramine produced more improvement than did placebo and chlordiazepoxide . By six and eight weeks a general , marked therapeutic advantage was found for imipramine relative to placebo and to chlordiazepoxide on measures of depression , anxiety , anger-hostility , interpersonal sensitivity , and global improvement .  Chlordiazepoxide-treated patients generally did significantly better on sleep difficulty but significantly worse on anger-hostility and interpersonal sensitivity than did imipramine- or placebo-treated patients
target: 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: 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 .