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: OBJECTIVE To address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type , severity , and duration of deficits that may be induced by these agents . As part of a placebo-controlled trial of alprazolam-XR ( extended release ) administered in combination with cognitive-behavioral therapy in patients with panic disorder , a battery of tests was used to measure neuropsychologic function .  Thirty-eight out patients were r and omly assigned to receive either alprazolam-XR or placebo . Dosages were titrated up so that the alprazolam group ( N = 18 ) received a mean dose of 4 mg/day ( reduced in two patients because of sedative side effects ) . Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessment s in each group . Both groups showed a statistically significant improvement from baseline to repeated assessment s on measures of attention , executive functioning , psychomotor speed , and visual memory ( p < 0.001 ) ; these gains were attributed to a practice effect . No significant changes were noted in measures of learning , verbal memory , or reaction time , and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function . These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders BACKGROUND Exposure to external phobic cues is an effective therapy for  panic/agoraphobia  but the value of exposure to interoceptive cues is unclear . AIMS R and omised controlled comparison in panic/agoraphobia of the effects of ( a ) external , ( b ) interceptive or ( c ) combined external and interoceptive self-exposure to ( d ) control subjects . METHOD Eighty out- patients were r and omised to a control group or to one of three forms of self-exposure treatment ( external , interoceptive , or combined ) . Each treatment included seven sessions over 10 weeks and daily self-exposure homework . Assessment s were at pre- and post-treatment and up to 1 year post-entry . Assessors remained blind during treatment . RESULTS The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year followup , and significantly more than did the control subjects . Rates of improvement on main outcome measures averaged 60 % at post-treatment and 77 % at follow-up . CONCLUSIONS The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term Pre-treatment predictors of treatment outcome were examined in a group of 144 patients with panic disorder and agoraphobia r and omly allocated to alprazolam+exposure ( AE ) , placebo+exposure ( PE ) , alprazolam+relaxation ( AR ) , and placebo+relaxation ( PR ) . First-time psychotropic medication use , severity of agoraphobic disability , and longer duration of illness predicted less global improvement at post-treatment . Pre-treatment severity of agoraphobia predicted less improvement both in the short- and the long-term . Predictors of poorer outcome at 6-month follow-up were older age , past history of depression , severity of phobia targets , and longer duration of illness . Sex , source of referral , pre-treatment depression-anxiety-panic , and expectancy from treatment did not relate to outcome Cognitive therapy ( CT ) is a specific and highly effective treatment for panic disorder ( PD ) . Treatment normally involves 12 - 15 1-hr sessions . In an attempt to produce a more cost-effective version , a briefer treatment that made extensive use of between-sessions patient self- study modules was created . Forty-three PD patients were r and omly allocated to full CT ( FCT ) , brief CT ( BCT ) , or a 3-month wait list . FCT and BCT were superior to wait list on all measures , and the gains obtained in treatment were maintained at 12-month follow-up . There were no significant differences between FCT and BCT . Both treatments had large ( approximately 3.0 ) and essentially identical effect sizes . BCT required 6.5 hr of therapist time , including booster sessions . Patients ' initial expectation of therapy success was negatively correlated with posttreatment panic-anxiety . Cognitive measures at the end of treatment predicted panic-anxiety at 12-month follow-up Objective The present study examined the prevalence of  panic disorder  with or without agoraphobia according to DSM-IV criteria in the Swedish general population . Method Data were obtained by means of a postal survey administrated to 1000 r and omly selected adults . The panic disorder module of the World Health Organization 's Composite International Diagnostic Interview ( CIDI ) was included in the survey . Results 12-month prevalence was estimated at 2.2 % ( CI 95 % 1.02 % – 3.38 % ) . There was a significant sex difference , with a greater prevalence for women ( 5.6 % ) compared to men ( 1 % ) . Conclusion The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world In a controlled trial of alprazolam and exposure in 154 patients with panic disorder with agoraphobia , relations between panic , anticipatory anxiety , and phobic avoidance were examined . The three symptoms were independent of one another at baseline and improved largely independently during treatment ; only early improvement in avoidance predicted global improvement after treatment . Global improvement was more related to reduction of avoidance than a decrease in panics . Panic was not a valuable outcome measure in panic disorder with agoraphobia We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy As part of the cross‐national collaborative panic study , a double‐blind comparison of alprazolam , imipramine and placebo was performed in Sc and inavian out patients with panic disorder according to DSM‐III ; 41 patients were r and omly allocated to each drug . Doses were increased for 3 weeks to an average of about 6 mg alprazolam , 150 mg imipramine and a corresponding number of placebo capsules , which were then given for 5 weeks . No more than supportive psychotherapy was given . Key symptoms were rated weekly . The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months . Compliance at 3 weeks was 95 % for alprazolam , 83 % for imipramine and 88 % for placebo ; at 8 weeks 95 % for alprazolam , 73 % for imipramine and 46 % for placebo . At 3 weeks plasma determination showed that the proportion taking  diazepam  outside the protocol was 0 % for alprazolam , 19 % for imipramine and 31 % for placebo ; at 8 weeks the corresponding proportions were 3 % , 11 % and 16 % . Intention‐to‐treat analysis showed that freedom from panic attacks was obtained for 68 % with alprazolam , 61 % with imipramine and 34 % with placebo . Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms . Globally rated by physicians and patients , about 60 % had complete remission  with alprazolam and imipramine and 30 % on placebo .  At least partial remission was obtained in about 85 % with alprazolam , 70 % with imipramine and 40 % with placebo . Alprazolam  had a more rapid onset of action than imipramine on all symptoms . Side effects were generally mild , with a preponderance of drowsiness  for alprazolam and anticholinergic effects for imipramine . Tapering was uneventful without significant discontinuation phenomena . During taper and follow‐up , several patients in remission relapsed , leaving approximately 30 % patients in complete remission in all groups . To obtain more stable improvement , either long‐term drug treatment or combinations of drug treatment and psychotherapy should be evaluated Compared the effectiveness of cognitive therapy and performance-based exposure as treatments for panic attacks . Subjects were 48 panicky individuals selected without regard to agoraphobic disability , and who varied widely in that respect . Subjects were assigned r and omly to either cognitive treatment , performance-based exposure treatment , a combined cognitive/performance treatment , or a no-treatment control condition . All three treatments led to marked and enduring improvements in panic , and did not differ from one another in effectiveness , whereas the control condition produced little benefit . However , on several measures of phobia and panic-related cognitions , performance exposure was significantly more effective than cognitive therapy . Degree of agoraphobic disability had a significant bearing on panic treatment effectiveness . Whereas 94 % of the low agoraphobia Ss were free of panic after treatment , only 52 % of the high agoraphobia Ss became panic-free . The findings suggest that when panic treatment research excludes people with serious phobias , as it has routinely done in recent years , an overly positive estimate of panic treatment effectiveness can result Fifty-seven chronic agoraphobic out patients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure , group versus individual exposure , and high versus medium anxiety arousal during individual exposure . The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up . Assess 
    Output:
    
agent
The review established the paucity of high quality evidence investigating the efficacy of psychotherapy combined with benzodiazepines for panic disorder .
Currently , there is inadequate evidence to assess the clinical effects of psychotherapy combined with benzodiazepines for patients who are diagnosed with 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: OBJECTIVE To address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type , severity , and duration of deficits that may be induced by these agents . As part of a placebo-controlled trial of alprazolam-XR ( extended release ) administered in combination with cognitive-behavioral therapy in patients with panic disorder , a battery of tests was used to measure neuropsychologic function .  Thirty-eight out patients were r and omly assigned to receive either alprazolam-XR or placebo . Dosages were titrated up so that the alprazolam group ( N = 18 ) received a mean dose of 4 mg/day ( reduced in two patients because of sedative side effects ) . Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessment s in each group . Both groups showed a statistically significant improvement from baseline to repeated assessment s on measures of attention , executive functioning , psychomotor speed , and visual memory ( p < 0.001 ) ; these gains were attributed to a practice effect . No significant changes were noted in measures of learning , verbal memory , or reaction time , and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function . These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders BACKGROUND Exposure to external phobic cues is an effective therapy for  panic/agoraphobia  but the value of exposure to interoceptive cues is unclear . AIMS R and omised controlled comparison in panic/agoraphobia of the effects of ( a ) external , ( b ) interceptive or ( c ) combined external and interoceptive self-exposure to ( d ) control subjects . METHOD Eighty out- patients were r and omised to a control group or to one of three forms of self-exposure treatment ( external , interoceptive , or combined ) . Each treatment included seven sessions over 10 weeks and daily self-exposure homework . Assessment s were at pre- and post-treatment and up to 1 year post-entry . Assessors remained blind during treatment . RESULTS The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year followup , and significantly more than did the control subjects . Rates of improvement on main outcome measures averaged 60 % at post-treatment and 77 % at follow-up . CONCLUSIONS The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term Pre-treatment predictors of treatment outcome were examined in a group of 144 patients with panic disorder and agoraphobia r and omly allocated to alprazolam+exposure ( AE ) , placebo+exposure ( PE ) , alprazolam+relaxation ( AR ) , and placebo+relaxation ( PR ) . First-time psychotropic medication use , severity of agoraphobic disability , and longer duration of illness predicted less global improvement at post-treatment . Pre-treatment severity of agoraphobia predicted less improvement both in the short- and the long-term . Predictors of poorer outcome at 6-month follow-up were older age , past history of depression , severity of phobia targets , and longer duration of illness . Sex , source of referral , pre-treatment depression-anxiety-panic , and expectancy from treatment did not relate to outcome Cognitive therapy ( CT ) is a specific and highly effective treatment for panic disorder ( PD ) . Treatment normally involves 12 - 15 1-hr sessions . In an attempt to produce a more cost-effective version , a briefer treatment that made extensive use of between-sessions patient self- study modules was created . Forty-three PD patients were r and omly allocated to full CT ( FCT ) , brief CT ( BCT ) , or a 3-month wait list . FCT and BCT were superior to wait list on all measures , and the gains obtained in treatment were maintained at 12-month follow-up . There were no significant differences between FCT and BCT . Both treatments had large ( approximately 3.0 ) and essentially identical effect sizes . BCT required 6.5 hr of therapist time , including booster sessions . Patients ' initial expectation of therapy success was negatively correlated with posttreatment panic-anxiety . Cognitive measures at the end of treatment predicted panic-anxiety at 12-month follow-up Objective The present study examined the prevalence of  panic disorder  with or without agoraphobia according to DSM-IV criteria in the Swedish general population . Method Data were obtained by means of a postal survey administrated to 1000 r and omly selected adults . The panic disorder module of the World Health Organization 's Composite International Diagnostic Interview ( CIDI ) was included in the survey . Results 12-month prevalence was estimated at 2.2 % ( CI 95 % 1.02 % – 3.38 % ) . There was a significant sex difference , with a greater prevalence for women ( 5.6 % ) compared to men ( 1 % ) . Conclusion The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world In a controlled trial of alprazolam and exposure in 154 patients with panic disorder with agoraphobia , relations between panic , anticipatory anxiety , and phobic avoidance were examined . The three symptoms were independent of one another at baseline and improved largely independently during treatment ; only early improvement in avoidance predicted global improvement after treatment . Global improvement was more related to reduction of avoidance than a decrease in panics . Panic was not a valuable outcome measure in panic disorder with agoraphobia We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy As part of the cross‐national collaborative panic study , a double‐blind comparison of alprazolam , imipramine and placebo was performed in Sc and inavian out patients with panic disorder according to DSM‐III ; 41 patients were r and omly allocated to each drug . Doses were increased for 3 weeks to an average of about 6 mg alprazolam , 150 mg imipramine and a corresponding number of placebo capsules , which were then given for 5 weeks . No more than supportive psychotherapy was given . Key symptoms were rated weekly . The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months . Compliance at 3 weeks was 95 % for alprazolam , 83 % for imipramine and 88 % for placebo ; at 8 weeks 95 % for alprazolam , 73 % for imipramine and 46 % for placebo . At 3 weeks plasma determination showed that the proportion taking  diazepam  outside the protocol was 0 % for alprazolam , 19 % for imipramine and 31 % for placebo ; at 8 weeks the corresponding proportions were 3 % , 11 % and 16 % . Intention‐to‐treat analysis showed that freedom from panic attacks was obtained for 68 % with alprazolam , 61 % with imipramine and 34 % with placebo . Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms . Globally rated by physicians and patients , about 60 % had complete remission  with alprazolam and imipramine and 30 % on placebo .  At least partial remission was obtained in about 85 % with alprazolam , 70 % with imipramine and 40 % with placebo . Alprazolam  had a more rapid onset of action than imipramine on all symptoms . Side effects were generally mild , with a preponderance of drowsiness  for alprazolam and anticholinergic effects for imipramine . Tapering was uneventful without significant discontinuation phenomena . During taper and follow‐up , several patients in remission relapsed , leaving approximately 30 % patients in complete remission in all groups . To obtain more stable improvement , either long‐term drug treatment or combinations of drug treatment and psychotherapy should be evaluated Compared the effectiveness of cognitive therapy and performance-based exposure as treatments for panic attacks . Subjects were 48 panicky individuals selected without regard to agoraphobic disability , and who varied widely in that respect . Subjects were assigned r and omly to either cognitive treatment , performance-based exposure treatment , a combined cognitive/performance treatment , or a no-treatment control condition . All three treatments led to marked and enduring improvements in panic , and did not differ from one another in effectiveness , whereas the control condition produced little benefit . However , on several measures of phobia and panic-related cognitions , performance exposure was significantly more effective than cognitive therapy . Degree of agoraphobic disability had a significant bearing on panic treatment effectiveness . Whereas 94 % of the low agoraphobia Ss were free of panic after treatment , only 52 % of the high agoraphobia Ss became panic-free . The findings suggest that when panic treatment research excludes people with serious phobias , as it has routinely done in recent years , an overly positive estimate of panic treatment effectiveness can result Fifty-seven chronic agoraphobic out patients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure , group versus individual exposure , and high versus medium anxiety arousal during individual exposure . The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up . Assess 
    Output:
    