human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 rem 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 rem 
    Output:
    