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: Recent animal models suggest that disturbances in serotonin type-1A receptor ( 5-HT1AR ) function may contribute to chronic anxiety , although it is not clear at all whether such models constitute relevant models for panic disorder ( PD ) in humans . The selective 5-HT1AR radiolig and [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide ( FCWAY ) permits in vivo assessment of central 5-HT1AR binding using positron emission tomography ( PET ) . We studied 16 unmedicated symptomatic out patients with PD and 15 matched healthy controls . Seven patients had an additional diagnosis of a current major depressive episode , however PD was the primary diagnosis . A 120 min PET study of  5-HT1AR  binding was acquired using a GE Advance scanner in three-dimensional mode . Using quantitative PET image analysis , regional values were obtained for [18F]-FCWAY volume of distribution ( DV ) , corrected for plasma protein binding , and K1 , the delivery rate of [18F]-FCWAY from plasma to tissue . MRI scanning was performed using a GE Signa Scanner ( 3.0 Tesla ) to provide an anatomical framework for image analysis and partial volume correction of PET data . PD patients showed lower DV in the anterior cingulate ( t = 4.3 ; p < 0.001 ) , posterior cingulate ( t = 4.1 ; p < 0.001 ) , and raphe ( t = 3.1 ; p = 0.004 ) . Comparing patients with PD , patients with PD and comorbid depression , and healthy controls revealed that DVs did not differ between PD patients and PD patients with comorbid depression , whereas both patient groups differed significantly from controls . These results provide for the first time in vivo evidence for the involvement of 5-HT1ARs in the pathophysiology of PD CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data Two groups of 12 out patients each ( six men and six women ) with generalized anxiety disorder , participated in this study . Each patient was treated single-blind with placebo during the first 7 days ( baseline ) , followed by a double-blind drug treatment period of 4 consecutive weeks ( active ) and ending again with 7 days single-blind placebo treatment ( washout ) . One group received buspirone 5 mg three times a day in the first week and continued with 10 mg in the morning , 5 mg in the afternoon , and 5 mg in the evening during the second , third , and fourth weeks . The other group received diazepam 5 mg three times a day in all 4 weeks . On the evening of the seventh day of each treatment week the  Hamilton Rating Scale for Anxiety and the Symptom Check List  ( 90 items ) were applied to assess the therapeutic effects , followed by an on-the-road driving test that started 1.5 hours after the last drug or placebo intake . The test consisted of operating an instrumented vehicle over a 100 kilometer highway circuit while attempting to maintain a constant speed and a steady lateral position within the right traffic lane . Two patients in the diazepam group were unable to complete their test after the first and second treatment week , respectively , because of serious sedative reactions . Both buspirone and diazepam were equally effective in reducing overall anxiety symptoms . The specific profiles showed that buspirone also reduced concomitant depressive symptoms and symptoms of interpersonal sensitivity and anger-hostility . In contrast , diazepam was found to be slightly more effective in reducing somatic symptoms and to positively affect sleep disturbances . Moreover , abrupt discontinuation of diazepam result ed in a relapse of psychic anxiety symptoms comparable with the placebo-baseline level and a partial relapse of somatic anxiety symptoms . Chronic treatment with buspirone had no significant effects on lateral position and speed control . In contrast , diazepam significantly impaired control of lateral position in the first 3 weeks of treatment . There was no significant impairment in the fourth treatment week and the placebo-washout week . Speed control was significantly impaired only in the first week . The relevance of the trend toward decreasing performance impairment during chronic treatment remains to be established BACKGROUND The change of psychopathological dimensions during treatment of panic disorder is attracting increasing interest . METHODS A population of subjects experiencing panic disorder with agoraphobia is evaluated with the French version of the factor structure of the Symptom Checklist 90 R ( SCL 90 R ) . Two groups of patients are compared : a group receiving cognitive behaviour therapy ( CBT ) combined with buspirone and a group receiving cognitive behaviour therapy combined with placebo .  RESULTS Comparative analysis of pre- and post-test changes between both groups completing treatment showed that the combination cognitive behaviour therapy plus buspirone provided better results than those in patients who had received cognitive behaviour therapy plus placebo . This difference between treatments did not persist at the 1-year follow-up , since , while results had been effectively maintained in the CBT plus buspirone group , the CBT plus placebo group continued to improve significantly for the target dimensions of treatment . CONCLUSIONS Psychopathological dimensions on the SCL 90 R show that combination of buspirone and cognitive behaviour therapy accelerates the behaviour modification process only in the short term The efficacy of buspirone for panic disorder was tested in 60 patients who met Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . ) criteria for panic disorder or agoraphobia with panic attacks . Patients were r and omly assigned to treatment with buspirone ( mean dose 29.5 mg/day ) , imipramine ( mean dose 140 mg/day ) , or placebo , and treated for 8 weeks after a 4- to 7-day placebo lead-in period . Patients with 4 or fewer attacks per month and those without attacks at the baseline visit were excluded from panic frequency comparisons . Both buspirone and imipramine tended to be better than placebo on total number of panic attacks , global psychopathology , and the Hamilton Anxiety rating scale , but end point differences among treatments were not statistically significant . At the end of the study , 25 % of the buspirone patients were panic-free , as were 7 % of the imipramine patients and 14 % of the placebo patients ; again , these differences were not statistically significant . The results of this study were inconclusive , partly because of the relatively small number of patients ( 10 - 11 ) completing the study in each treatment group , and partly because of a robust placebo response in this population . Possible reasons for this high placebo response are discussed , as well as suggestions for changes in study design for future studies 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 Proper evaluation of anxiolytic therapy , involving the possible use of rating scales as well as the physician 's skill in observation and communication , is essential in identifying the most appropriate treatment for a given patient and facilitating the management of therapy . These issues are discussed herein , using the clinical trials of buspirone , a new , nonsedating antianxiety agent , as a model for the process of drug selection Thirty-six patients with generalised anxiety disorder , panic disorder or agoraphobia with panic attacks , diagnosed by DSM-III criteria , were treated with a new non-benzodiazepine anti-anxiety drug , buspirone , and with diazepam and placebo , in a cross-over design . Each patient took buspirone , diazepam and placebo for one week each in flexible dosage and balanced order . Ratings of symptomatology using the Comprehensive Psychopathological Rating Scale were made after each week 's treatment and a sub-scale used for measuring anxiety change alone was used separately . There was no overall difference in efficacy between the drugs , but when the scores for individual symptoms were analysed , diazepam was significantly superior to the other treatments for the symptom of muscle tension only . The results suggest that the common practice of giving short-term therapy with tranquilising drugs for anxiety in primary care is pharmacologically suspect Sixty-five in patients of a psychosomatic hospital in the Federal Republic of Germany with the diagnosis of anxiety neurosis ( n = 31 ) or neurotic depression ( n = 34 ) as defined by the International Classification of Disease ( ICD-9 ) , were r and omized to a 4-week course of  ipsapirone at 7.5 mg t.i.d . or placebo in a prospect i ve , double-blind clinical trial to assess safety , tolerability , and efficacy . This article reports the efficacy results for those patients with the diagnosis of neurotic depression . The primary efficacy variable for patients with neurotic depression was the change from baseline in the Hamilton Rating Scale for Depression ( HAM-D ) at 4 weeks of treatment . Considering all of the r and omized patients with neurotic depression ( n = 34 , the intent-to-treat population ) , the mean change from baseline in the HAM-D at Week 4 ( observed cases ) was -13.13 + /- 6.06 ( n = 16 ) for the ipsapirone group , and -3.19 + /- 5.99 ( n = 16 ) for the placebo group ( p less than .001 ) . A parallel analysis of the change from baseline in the Core Depression score of the HAM-D ( defined as the sum of items 1 , 2 , 3 , 7 , and 8) also showed a significant treatment difference ( p less than .01 ) . Results were similar for the intent-to-treat population , last observation carried forward . Safety and tolerability were evaluated for all study patients independent of diagnosis . Treatment-emergent events ( n = 65 ) were reported by 76 percent of patients treated with ipsapirone ( n = 33 ) and by 38 percent of patients treated with placebo ( n = 32 ) . ( ABSTRACT TRUNCATED AT 250 WORDS In this double-blind study , 56 adult psychoneurotic out patients with a primary diagnosis of anxiety neurosis were r and omly assigned to receive buspirone ( N = 18 ) , diazepam ( N = 20 ) , or placebo ( 
    Output:
    
agent
The efficacy of azapirones is uncertain due to the lack of meta-analysable data for the primary outcome and low- quality evidence for secondary efficacy outcomes .
A small amount of moderate- quality evidence suggested that the acceptability of azapirones for panic disorder was lower than for placebo .
If further research is to be conducted , studies with larger sample sizes , with different azapirones and with less risk of bias are necessary to draw firm conclusions regarding azapirones for panic disorder
***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: Recent animal models suggest that disturbances in serotonin type-1A receptor ( 5-HT1AR ) function may contribute to chronic anxiety , although it is not clear at all whether such models constitute relevant models for panic disorder ( PD ) in humans . The selective 5-HT1AR radiolig and [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide ( FCWAY ) permits in vivo assessment of central 5-HT1AR binding using positron emission tomography ( PET ) . We studied 16 unmedicated symptomatic out patients with PD and 15 matched healthy controls . Seven patients had an additional diagnosis of a current major depressive episode , however PD was the primary diagnosis . A 120 min PET study of  5-HT1AR  binding was acquired using a GE Advance scanner in three-dimensional mode . Using quantitative PET image analysis , regional values were obtained for [18F]-FCWAY volume of distribution ( DV ) , corrected for plasma protein binding , and K1 , the delivery rate of [18F]-FCWAY from plasma to tissue . MRI scanning was performed using a GE Signa Scanner ( 3.0 Tesla ) to provide an anatomical framework for image analysis and partial volume correction of PET data . PD patients showed lower DV in the anterior cingulate ( t = 4.3 ; p < 0.001 ) , posterior cingulate ( t = 4.1 ; p < 0.001 ) , and raphe ( t = 3.1 ; p = 0.004 ) . Comparing patients with PD , patients with PD and comorbid depression , and healthy controls revealed that DVs did not differ between PD patients and PD patients with comorbid depression , whereas both patient groups differed significantly from controls . These results provide for the first time in vivo evidence for the involvement of 5-HT1ARs in the pathophysiology of PD CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data Two groups of 12 out patients each ( six men and six women ) with generalized anxiety disorder , participated in this study . Each patient was treated single-blind with placebo during the first 7 days ( baseline ) , followed by a double-blind drug treatment period of 4 consecutive weeks ( active ) and ending again with 7 days single-blind placebo treatment ( washout ) . One group received buspirone 5 mg three times a day in the first week and continued with 10 mg in the morning , 5 mg in the afternoon , and 5 mg in the evening during the second , third , and fourth weeks . The other group received diazepam 5 mg three times a day in all 4 weeks . On the evening of the seventh day of each treatment week the  Hamilton Rating Scale for Anxiety and the Symptom Check List  ( 90 items ) were applied to assess the therapeutic effects , followed by an on-the-road driving test that started 1.5 hours after the last drug or placebo intake . The test consisted of operating an instrumented vehicle over a 100 kilometer highway circuit while attempting to maintain a constant speed and a steady lateral position within the right traffic lane . Two patients in the diazepam group were unable to complete their test after the first and second treatment week , respectively , because of serious sedative reactions . Both buspirone and diazepam were equally effective in reducing overall anxiety symptoms . The specific profiles showed that buspirone also reduced concomitant depressive symptoms and symptoms of interpersonal sensitivity and anger-hostility . In contrast , diazepam was found to be slightly more effective in reducing somatic symptoms and to positively affect sleep disturbances . Moreover , abrupt discontinuation of diazepam result ed in a relapse of psychic anxiety symptoms comparable with the placebo-baseline level and a partial relapse of somatic anxiety symptoms . Chronic treatment with buspirone had no significant effects on lateral position and speed control . In contrast , diazepam significantly impaired control of lateral position in the first 3 weeks of treatment . There was no significant impairment in the fourth treatment week and the placebo-washout week . Speed control was significantly impaired only in the first week . The relevance of the trend toward decreasing performance impairment during chronic treatment remains to be established BACKGROUND The change of psychopathological dimensions during treatment of panic disorder is attracting increasing interest . METHODS A population of subjects experiencing panic disorder with agoraphobia is evaluated with the French version of the factor structure of the Symptom Checklist 90 R ( SCL 90 R ) . Two groups of patients are compared : a group receiving cognitive behaviour therapy ( CBT ) combined with buspirone and a group receiving cognitive behaviour therapy combined with placebo .  RESULTS Comparative analysis of pre- and post-test changes between both groups completing treatment showed that the combination cognitive behaviour therapy plus buspirone provided better results than those in patients who had received cognitive behaviour therapy plus placebo . This difference between treatments did not persist at the 1-year follow-up , since , while results had been effectively maintained in the CBT plus buspirone group , the CBT plus placebo group continued to improve significantly for the target dimensions of treatment . CONCLUSIONS Psychopathological dimensions on the SCL 90 R show that combination of buspirone and cognitive behaviour therapy accelerates the behaviour modification process only in the short term The efficacy of buspirone for panic disorder was tested in 60 patients who met Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . ) criteria for panic disorder or agoraphobia with panic attacks . Patients were r and omly assigned to treatment with buspirone ( mean dose 29.5 mg/day ) , imipramine ( mean dose 140 mg/day ) , or placebo , and treated for 8 weeks after a 4- to 7-day placebo lead-in period . Patients with 4 or fewer attacks per month and those without attacks at the baseline visit were excluded from panic frequency comparisons . Both buspirone and imipramine tended to be better than placebo on total number of panic attacks , global psychopathology , and the Hamilton Anxiety rating scale , but end point differences among treatments were not statistically significant . At the end of the study , 25 % of the buspirone patients were panic-free , as were 7 % of the imipramine patients and 14 % of the placebo patients ; again , these differences were not statistically significant . The results of this study were inconclusive , partly because of the relatively small number of patients ( 10 - 11 ) completing the study in each treatment group , and partly because of a robust placebo response in this population . Possible reasons for this high placebo response are discussed , as well as suggestions for changes in study design for future studies 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 Proper evaluation of anxiolytic therapy , involving the possible use of rating scales as well as the physician 's skill in observation and communication , is essential in identifying the most appropriate treatment for a given patient and facilitating the management of therapy . These issues are discussed herein , using the clinical trials of buspirone , a new , nonsedating antianxiety agent , as a model for the process of drug selection Thirty-six patients with generalised anxiety disorder , panic disorder or agoraphobia with panic attacks , diagnosed by DSM-III criteria , were treated with a new non-benzodiazepine anti-anxiety drug , buspirone , and with diazepam and placebo , in a cross-over design . Each patient took buspirone , diazepam and placebo for one week each in flexible dosage and balanced order . Ratings of symptomatology using the Comprehensive Psychopathological Rating Scale were made after each week 's treatment and a sub-scale used for measuring anxiety change alone was used separately . There was no overall difference in efficacy between the drugs , but when the scores for individual symptoms were analysed , diazepam was significantly superior to the other treatments for the symptom of muscle tension only . The results suggest that the common practice of giving short-term therapy with tranquilising drugs for anxiety in primary care is pharmacologically suspect Sixty-five in patients of a psychosomatic hospital in the Federal Republic of Germany with the diagnosis of anxiety neurosis ( n = 31 ) or neurotic depression ( n = 34 ) as defined by the International Classification of Disease ( ICD-9 ) , were r and omized to a 4-week course of  ipsapirone at 7.5 mg t.i.d . or placebo in a prospect i ve , double-blind clinical trial to assess safety , tolerability , and efficacy . This article reports the efficacy results for those patients with the diagnosis of neurotic depression . The primary efficacy variable for patients with neurotic depression was the change from baseline in the Hamilton Rating Scale for Depression ( HAM-D ) at 4 weeks of treatment . Considering all of the r and omized patients with neurotic depression ( n = 34 , the intent-to-treat population ) , the mean change from baseline in the HAM-D at Week 4 ( observed cases ) was -13.13 + /- 6.06 ( n = 16 ) for the ipsapirone group , and -3.19 + /- 5.99 ( n = 16 ) for the placebo group ( p less than .001 ) . A parallel analysis of the change from baseline in the Core Depression score of the HAM-D ( defined as the sum of items 1 , 2 , 3 , 7 , and 8) also showed a significant treatment difference ( p less than .01 ) . Results were similar for the intent-to-treat population , last observation carried forward . Safety and tolerability were evaluated for all study patients independent of diagnosis . Treatment-emergent events ( n = 65 ) were reported by 76 percent of patients treated with ipsapirone ( n = 33 ) and by 38 percent of patients treated with placebo ( n = 32 ) . ( ABSTRACT TRUNCATED AT 250 WORDS In this double-blind study , 56 adult psychoneurotic out patients with a primary diagnosis of anxiety neurosis were r and omly assigned to receive buspirone ( N = 18 ) , diazepam ( N = 20 ) , or placebo ( 
    Output:
    