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: The efficacy of tricyclics and benzodiazepines in the short term ( approximately 2 - 4 months ) treatment of panic disorder is well demonstrated , but efficacy over the longer term is not considered established . The present study provided systematic data from a double blind comparison of maintenance therapy ( up to 8 months ) of panic disorder with or without agoraphobia with alprazolam , imipramine , or placebo in 181 patients who had responded to the same regimen in a r and omized 8-week treatment trial . All three groups had improved during the first 2 months ( active treatments more than placebo and about equal to each other ) , and all maintained or extended their improvement over the next 6 months without any significant change in dose . More than twice as many alprazolam and imipramine than placebo patients ( 15 % ) remained in treatment for the full 8 months and did slightly better on symptom measures than the remaining placebo patients . Both medications were well tolerated during the maintenance period . The data suggest sustained efficacy and safety of imipramine and alprazolam over an extended period . More specifically , they suggest that tolerance does not develop to the therapeutic effects of either drug 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 Seventy-nine patients with panic disorder were r and omized to an 8-week double-blind treatment with alprazolam , imipramine , or placebo . Patients kept daily records of panic attacks , activity , anxiety , sleep , and medication use . Weekly measures of anxiety , depression , somatic symptoms , fears , avoidance , disability , and improvement were obtained . All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures . By physician and patient global assessment , patients receiving alprazolam or imipramine were significantly better than patients on placebo . The alprazolam effects were apparent by week 1 ; the imipramine effects by week 4 . All groups showed significant reductions in anxiety , depression , somatic measures , and panic attack frequency . At 8 weeks , patients in the alprazolam group reported significantly less fear than patients in the other two groups . Subjects in the imipramine group showed a significant increase in heart rate and blood pressure The paper consists of two parts . A review of the relationship of panic disorder to the phobic states and the treatment of these disorders by means of tricyclic antidepressants , MAOIs , beta blocking drugs and benzodiazepines . A double blind study of alprazolam and placebo in 118 patients with agoraphobia and panic is presented . In an eight week study alprazolam was found to be significantly superior to placebo in the treatment of panic attacks , phobic avoidance , anticipatory anxiety and general anxiety BACKGROUND The serotonin selective reuptake inhibitors are increasingly being used for the treatment of panic disorder . We examined the efficacy and safety of the serotonin selective reuptake inhibitor sertraline hydrochloride in patients with panic disorder . METHODS One hundred seventy-six nondepressed out patients with panic disorder , with or without agoraphobia , from 10 sites followed identical protocol s that used a flexible-dose design . After 2 weeks of single-blind placebo , patients were r and omly assigned to 10 weeks of double-blind , flexible-dose treatment with either sertraline hydrochloride ( 50 - 200 mg/d ) or placebo . RESULTS Sertraline-treated patients exhibited significantly greater improvement ( P=.01 ) at end point than did patients treated with placebo for the primary outcome variable , panic attack frequency . Significant differences between groups were also evident for clinician and patient assessment s of improvement as measured by the Clinical Global Impression Improvement ( P=.01 ) and Severity ( P=.009 ) Scales , Panic Disorder Severity Scale ratings ( P=.03 ) , high end-state function assessment ( P=.03 ) , Patient Global Evaluation rating ( P=.01 ) , and quality of life scores ( P=.003 ) . Adverse events , generally characterized as either mild or moderate , were not significantly different in overall incidence between the sertraline and placebo groups . CONCLUSION Results support the safety and efficacy of sertraline for the short-term treatment of patients with panic disorder This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode , Dysthymia , or Depressive Disorder NOS . The study 's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam , imipramine and placebo on anxiety outcomes . A placebo-controlled , double-blind , parallel r and om assignment design was utilized over a total of 16 weeks . There was no medication effect on panic outcomes . At endpoint , percent of anticipatory anxiety ( i.e. , time spent worrying about having an anxiety attack ) was significantly lower in the patients taking active medications vs. placebo .  Phobic measures were significantly improved by alprazolam , vs. both imipramine and placebo early in the study ; however , by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms . In addition , both active medications were significantly more effective than placebo in reducing depression . The same efficacy pattern ( i.e. , active medications superior to placebo ) was observed on measures of general functioning . Importantly , there were no significant interactions observed between medication and presence of major depression on the depression measures , indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression . Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range , these results may not be transferrable to patients with panic disorder and severe major depression This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week , placebo-controlled trial of alprazolam and imipramine  ( n = 126 ) . Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment . Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4 . At endpoint , the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance . This relationship was not evident for completers , suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced This paper reports the results of a double-blind comparison of fixed daily doses of 6 mg of alprazolam , 2 mg of alprazolam , 225 mg of imipramine , and placebo for 8 weeks in 81 patients who met DSM-III criteria for panic disorder with or without agoraphobia . Final scores on eight clinical measures were analyzed from all patients who entered the study and from the subset who completed at least 4 weeks of treatment . Eighty-six percent of the high-dose alprazolam patients completed the study . Only 50 % of the imipramine patients completed 8 weeks of treatment , apparently because of activation early in treatment and slow onset of therapeutic effects . This study confirmed the therapeutic effectiveness and safety of alprazolam  , especially at the higher dose , in panic disorder . It also confirmed the therapeutic effectiveness of imipramine among patients who tolerated the drug . It suggested the usefulness of a flexible , individual approach to dose escalation with imipramine . Method ologically the study underscored the importance of using multiple approaches to the analysis of clinical data from therapeutic trials of psychotropic agents with complex effects that may contribute to patients ' premature termination Date from a panic disorder treatment study with 506 patients , comparing alprazolam and placebo in a double-blind manner for 8 weeks , were analyzed to identify demographic and clinical characteristics of the patients that might predict response to treatment . The strongest predictors of response to alprazolam were age over 40 , and lower baseline levels of anxiety and phobic symptoms . Predictors of response to placebo were weaker and , in addition to lower levels anxiety and panic attacks , included a lack of previous psychiatric treatment A recently reported multinational , 8-week double-blind , placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam . We now report the results of a three-site , 6-week , double-blind , fixed-dose study comparing alprazolam 2 mg , alprazolam 6 mg , and placebo in 94 patients with panic disorder with or without agoraphobia . Both alprazolam treatment groups ( 6 mg and 2 mg ) improved significantly more than did the placebo treatment group on most outcome measures . Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned , although the pattern of treatment response across measures suggested a dose effect . Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects , which may have contributed to the limited differences between groups at study end . The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder 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 Two hundred six out patients with panic disorder and agoraphobia were r and omly assigned to receive 4 weeks of treatment with placebo or sustained-release adinazolam under double-blind conditions . Eighty-eight percent of patients receiving drug and 85 % of patients receiving placebo remained in the study at week 4 . This report describes the “ intent-to-treat ” analysis of 202 patients who made at least one follow-up visit after r and omization at baseline . On the basis of the Clinical Global Impressions-Improvement Scale , 69.7 % of the adinazolam-treated patients were much or very much improved compared with 39.6 % of the placebo-treated patients at week 4 or end-point ( p = 0.0001 ) . At week 4 , panic attacks were completely blocked in 57.1 % of ad 
    Output:
    
agent
Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo .
Low- quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders .
Due to these limitations , our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice .
***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: The efficacy of tricyclics and benzodiazepines in the short term ( approximately 2 - 4 months ) treatment of panic disorder is well demonstrated , but efficacy over the longer term is not considered established . The present study provided systematic data from a double blind comparison of maintenance therapy ( up to 8 months ) of panic disorder with or without agoraphobia with alprazolam , imipramine , or placebo in 181 patients who had responded to the same regimen in a r and omized 8-week treatment trial . All three groups had improved during the first 2 months ( active treatments more than placebo and about equal to each other ) , and all maintained or extended their improvement over the next 6 months without any significant change in dose . More than twice as many alprazolam and imipramine than placebo patients ( 15 % ) remained in treatment for the full 8 months and did slightly better on symptom measures than the remaining placebo patients . Both medications were well tolerated during the maintenance period . The data suggest sustained efficacy and safety of imipramine and alprazolam over an extended period . More specifically , they suggest that tolerance does not develop to the therapeutic effects of either drug 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 Seventy-nine patients with panic disorder were r and omized to an 8-week double-blind treatment with alprazolam , imipramine , or placebo . Patients kept daily records of panic attacks , activity , anxiety , sleep , and medication use . Weekly measures of anxiety , depression , somatic symptoms , fears , avoidance , disability , and improvement were obtained . All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures . By physician and patient global assessment , patients receiving alprazolam or imipramine were significantly better than patients on placebo . The alprazolam effects were apparent by week 1 ; the imipramine effects by week 4 . All groups showed significant reductions in anxiety , depression , somatic measures , and panic attack frequency . At 8 weeks , patients in the alprazolam group reported significantly less fear than patients in the other two groups . Subjects in the imipramine group showed a significant increase in heart rate and blood pressure The paper consists of two parts . A review of the relationship of panic disorder to the phobic states and the treatment of these disorders by means of tricyclic antidepressants , MAOIs , beta blocking drugs and benzodiazepines . A double blind study of alprazolam and placebo in 118 patients with agoraphobia and panic is presented . In an eight week study alprazolam was found to be significantly superior to placebo in the treatment of panic attacks , phobic avoidance , anticipatory anxiety and general anxiety BACKGROUND The serotonin selective reuptake inhibitors are increasingly being used for the treatment of panic disorder . We examined the efficacy and safety of the serotonin selective reuptake inhibitor sertraline hydrochloride in patients with panic disorder . METHODS One hundred seventy-six nondepressed out patients with panic disorder , with or without agoraphobia , from 10 sites followed identical protocol s that used a flexible-dose design . After 2 weeks of single-blind placebo , patients were r and omly assigned to 10 weeks of double-blind , flexible-dose treatment with either sertraline hydrochloride ( 50 - 200 mg/d ) or placebo . RESULTS Sertraline-treated patients exhibited significantly greater improvement ( P=.01 ) at end point than did patients treated with placebo for the primary outcome variable , panic attack frequency . Significant differences between groups were also evident for clinician and patient assessment s of improvement as measured by the Clinical Global Impression Improvement ( P=.01 ) and Severity ( P=.009 ) Scales , Panic Disorder Severity Scale ratings ( P=.03 ) , high end-state function assessment ( P=.03 ) , Patient Global Evaluation rating ( P=.01 ) , and quality of life scores ( P=.003 ) . Adverse events , generally characterized as either mild or moderate , were not significantly different in overall incidence between the sertraline and placebo groups . CONCLUSION Results support the safety and efficacy of sertraline for the short-term treatment of patients with panic disorder This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode , Dysthymia , or Depressive Disorder NOS . The study 's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam , imipramine and placebo on anxiety outcomes . A placebo-controlled , double-blind , parallel r and om assignment design was utilized over a total of 16 weeks . There was no medication effect on panic outcomes . At endpoint , percent of anticipatory anxiety ( i.e. , time spent worrying about having an anxiety attack ) was significantly lower in the patients taking active medications vs. placebo .  Phobic measures were significantly improved by alprazolam , vs. both imipramine and placebo early in the study ; however , by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms . In addition , both active medications were significantly more effective than placebo in reducing depression . The same efficacy pattern ( i.e. , active medications superior to placebo ) was observed on measures of general functioning . Importantly , there were no significant interactions observed between medication and presence of major depression on the depression measures , indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression . Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range , these results may not be transferrable to patients with panic disorder and severe major depression This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week , placebo-controlled trial of alprazolam and imipramine  ( n = 126 ) . Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment . Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4 . At endpoint , the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance . This relationship was not evident for completers , suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced This paper reports the results of a double-blind comparison of fixed daily doses of 6 mg of alprazolam , 2 mg of alprazolam , 225 mg of imipramine , and placebo for 8 weeks in 81 patients who met DSM-III criteria for panic disorder with or without agoraphobia . Final scores on eight clinical measures were analyzed from all patients who entered the study and from the subset who completed at least 4 weeks of treatment . Eighty-six percent of the high-dose alprazolam patients completed the study . Only 50 % of the imipramine patients completed 8 weeks of treatment , apparently because of activation early in treatment and slow onset of therapeutic effects . This study confirmed the therapeutic effectiveness and safety of alprazolam  , especially at the higher dose , in panic disorder . It also confirmed the therapeutic effectiveness of imipramine among patients who tolerated the drug . It suggested the usefulness of a flexible , individual approach to dose escalation with imipramine . Method ologically the study underscored the importance of using multiple approaches to the analysis of clinical data from therapeutic trials of psychotropic agents with complex effects that may contribute to patients ' premature termination Date from a panic disorder treatment study with 506 patients , comparing alprazolam and placebo in a double-blind manner for 8 weeks , were analyzed to identify demographic and clinical characteristics of the patients that might predict response to treatment . The strongest predictors of response to alprazolam were age over 40 , and lower baseline levels of anxiety and phobic symptoms . Predictors of response to placebo were weaker and , in addition to lower levels anxiety and panic attacks , included a lack of previous psychiatric treatment A recently reported multinational , 8-week double-blind , placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam . We now report the results of a three-site , 6-week , double-blind , fixed-dose study comparing alprazolam 2 mg , alprazolam 6 mg , and placebo in 94 patients with panic disorder with or without agoraphobia . Both alprazolam treatment groups ( 6 mg and 2 mg ) improved significantly more than did the placebo treatment group on most outcome measures . Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned , although the pattern of treatment response across measures suggested a dose effect . Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects , which may have contributed to the limited differences between groups at study end . The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder 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 Two hundred six out patients with panic disorder and agoraphobia were r and omly assigned to receive 4 weeks of treatment with placebo or sustained-release adinazolam under double-blind conditions . Eighty-eight percent of patients receiving drug and 85 % of patients receiving placebo remained in the study at week 4 . This report describes the “ intent-to-treat ” analysis of 202 patients who made at least one follow-up visit after r and omization at baseline . On the basis of the Clinical Global Impressions-Improvement Scale , 69.7 % of the adinazolam-treated patients were much or very much improved compared with 39.6 % of the placebo-treated patients at week 4 or end-point ( p = 0.0001 ) . At week 4 , panic attacks were completely blocked in 57.1 % of ad 
    Output:
    