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: Background Open-label quetiapine coadministration with SSRI therapy , in a diagnostically mixed sample of comorbid anxiety patients , offered additional anxiolytic benefit . Therefore , we design ed the following controlled trial to confirm these findings in a comorbid , SSRI-resistant , panic disorder ( PD ) patient sample . Methods This was a single-site , double-blind , placebo-controlled  ( PLAC ) , r and omized , parallel group ( 2 groups ) , 8-week , quetiapine extended release ( XR ) coadministration trial . SSRI resistance was determined either historically or prospect ively . Patients were r and omized if they remained moderately ill ( CGI-S score ≥ 4 )  . Change in the PDSS scale total score was the primary efficacy outcome measure . Responders were identified as those with a ≥50 % decrease from their baseline PDSS score . In the early weeks of therapy , XR was flexibly and gradually titrated from 50 to 400 mg/day . Results 43 patients were screened in total , and 26 of these were r and omized and evaluable . 21 patients ( 78 % of the r and omized group ) completed the trial ( 10 XR ; 11 PLAC ) . The endpoint quetiapine XR mean daily dose ± SD was 150 ± 106 mg . While , in the sample as a whole , there was improvement in PDSS scores across the 8-week trial ( ANOVA main effect of time , F = 10.9 , df8,192 , p < 0.0001 ) , the treatment × time interaction effect was not statistically significant ( F = 0.8 , df8,192 , p = 0.61 ) . There was no between-group difference in responder frequency at endpoint . Conclusions This proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD . Quetiapine XR was generally well-tolerated . Important limitations were the small sample size , and the relatively low average dose of quetiapine XR used . Clinical Trials.gov ID # : Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam  ( n = 47 ) and paroxetine  ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P < 0.001 ) . The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies . This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder . Patients who satisfactorily completed a 12-week , double-blind , placebo-controlled study of paroxetine and clomipramine  could choose to continue receiving their r and omized treatment for a further 36 weeks . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . In total , 176 patients were included in the intention-to-treat population . The number of full panic attacks decreased in all three groups during the 12-week study , and improvements continued with long-term therapy . Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks , and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks . There were no significant differences between paroxetine and clomipramine . The proportion of patients who withdrew from the study due to adverse effects  was greater in the clomipramine group ( 19 % ) than in either the paroxetine group ( 7 % ) or the placebo group ( 9 % ) . Paroxetine was significantly more effective than placebo and as effective as ( but better tolerated than ) clomipramine in the long-term treatment of panic disorder . Not only was efficacy maintained , but continued improvement was also seen , indicating the importance of long-term treatment in patients with panic disorder Non-response to pharmacotherapy for panic disorder ( PD ) is a well-documented problem . However , little information exists to guide next-step strategies for these non-responders . In addition to pharmacologic augmentation strategies , several studies support the efficacy of cognitive-behavior therapy ( CBT ) for these patients , although data on long-term outcomes has been lacking . In this study , we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy . Sustained significant benefit was found for all dimensional outcome scores , and nearly two-thirds of the sample met remission criteria . This occurred with reductions in medication use over the follow-up period . Negative predictors of remission status included comorbid dysthymia , social phobia , and generalized anxiety disorder . These results provide additional evidence for the efficacy of CBT for medication non-responders with PD Agoraphobia in panic disorder ( PD ) has been related to abnormal balance system function . Vision influences balance and behavioural adaptations ; peripheral vision influences orienting and fast defensive reactions whereas central vision analyzes details of objects . We have hypothesized that the abnormal balance function in PD could be mainly related to peripheral vision as part of a defensive alarm system in the brain . In 25 patients with PD and agoraphobia and 31 healthy controls we assessed , by posturography ,  balance system reactivity to video-films projected in peripheral and central visual fields ( r and omized sequence ) . Length , velocity and surface of body sway were calculated . Patients increased their body sway during peripheral stimulation , whereas controls did not ; the two groups showed a similar increase of body sway during central stimulation . Anxiety levels during peripheral stimulation significantly influenced the postural response in the group of patients . These preliminary results suggest that the higher visual sensitivity to peripheral stimulation in patients with PD and agoraphobia may be linked to a more active " visual alarm system " involving visual , vestibular and limbic areas that might influence the development of agoraphobia in situations where environmental stimuli are uncertain Experimental evidence suggests that panic disorder is characterized by abnormalities in the balance system function and that these abnormalities might be related to the severity of agoraphobic avoidance . Since the balance system can be modulated by the serotonergic system , we investigated the effect of a 6‐week treatment with citalopram on the balance system function in patients with panic disorder . Fifteen patients with panic disorder with/without agoraphobia underwent static posturography on days 0 and 42 . Static posturography and clinical assessment s were carried out by different investigators who were blind to each other . Static posturography showed high percentages of abnormal scores . Patients with no or low agoraphobic avoidance showed less abnormal posturographic measures than those with moderate to severe agoraphobia . After 6 weeks of treatment with citalopram there was a significant decrease of four out of six posturography measures in eyes‐closed and neck extension conditions , whereas no significant effect was found in the eyes‐open condition . This is the first report that suggests that the modulation of the serotonergic system can improve the balance system function in patients with panic disorder , particularly when visual information is lacking . In addition , our findings confirm the observation that many patients with panic disorder have abnormalities in their balance system function , supporting the idea that these abnormalities are mainly related to agoraphobic avoidance . Depression and Anxiety 17:101–106 , 2003 . © 2003 Wiley‐Liss , INTRODUCTION Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder ( PD ) . However preliminary studies suggested that reboxetine might be effective in the treatment of PD . We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD . METHODS Sixty-eight patients with PD were assigned to treatment groups in a single-blind , r and omized design . Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Side effects were also recorded . RESULTS Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one . Vice versa we did not find any significant differences for other outcome measures . Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group . CONCLUSIONS The results showed a greater effect of paroxetine on panic attacks than reboxetine , while no differences for anticipatory anxiety and avoidance were found , suggesting a different role of noradrenaline and serotonin in the treatment of PD Abstract : The effects of short treatments ( 7 days ) with paroxetine and with reboxetine on the reactivity to inhalations of 35 % carbon dioxide (CO2)/65 % oxygen ( O2 ) were compared in 28 patients with Panic Disorder who had positive responses to 35 % CO2 inhalations . A double-blind , r and omized design was applied . Each patient was given the 35 % CO2 challenge on days 0 ( before starting the treatment ) and 7 . Anxiety reactivity to CO2 decreased significantly with both drugs but the decrease was significantly stronger in the group treated with paroxetine . The rate of patients whose reactivity has reduced of at least 50 % after 7 days was significantly higher in the group treated with paroxetine ( 10/14 , 71.5 % ) than in the one treated with reboxetine ( 3/14 , 21.5 % ) . These results indicate that the modulation of the serotonergic system is more relevant for CO2 hyperreactivity than the modulation of the noradrenergic one Previous studies indicate that serotonin reuptake inhibitors do not appear to have serious cardiac side effects . However , the effects of these agents on respiratory measures have not been studied in detail . Several studies indicate that patients with anxiety exhibit irregular breathing patterns as measured by tidal volume and respiratory rate . In this study , we evaluated the effects of a serotonin reuptake inhibitor , paroxetine , on respiratory variability in patients with panic disorder ( n = 13 ) , using linear and nonlinear measures of regularity , approximate entropy ( APEN ) and a measure of chaos , the largest Lyapunov exponent ( LLE ) , with pre- and posttreatment lung volume time series ( 256 s long sample d at 4 Hz ) . Our results show that paroxetine significantly decreases some of the linear measures of variability and supine APEN and st and ing LLE of lung volume series after successful treatment . The implication s of these findings on respiratory and cardiovascular function have been discussed The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well toler 
    Output:
    
agent
Quetiapine extended-release augmentation has not been found to be beneficial , in comparison to placebo , in non-responders to previously recommended pharmacotherapy .
In non-responders to cognitive behavioral therapy ( CBT ) , switching to paroxetine/citalopram has been found to be more effective than continuing CBT .
Acceptance and commitment therapy ( ACT ) has shown some improvement in patients ’ resistance to previous psychological/pharmacological interventions compared with a waiting-list condition .
Prolonged pharmacotherapy may produce significant improvement in patients with unsatisfactory response to short-term pharmacotherapy  , while switching to pharmacotherapy may help non-responders to CBT .
***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: Background Open-label quetiapine coadministration with SSRI therapy , in a diagnostically mixed sample of comorbid anxiety patients , offered additional anxiolytic benefit . Therefore , we design ed the following controlled trial to confirm these findings in a comorbid , SSRI-resistant , panic disorder ( PD ) patient sample . Methods This was a single-site , double-blind , placebo-controlled  ( PLAC ) , r and omized , parallel group ( 2 groups ) , 8-week , quetiapine extended release ( XR ) coadministration trial . SSRI resistance was determined either historically or prospect ively . Patients were r and omized if they remained moderately ill ( CGI-S score ≥ 4 )  . Change in the PDSS scale total score was the primary efficacy outcome measure . Responders were identified as those with a ≥50 % decrease from their baseline PDSS score . In the early weeks of therapy , XR was flexibly and gradually titrated from 50 to 400 mg/day . Results 43 patients were screened in total , and 26 of these were r and omized and evaluable . 21 patients ( 78 % of the r and omized group ) completed the trial ( 10 XR ; 11 PLAC ) . The endpoint quetiapine XR mean daily dose ± SD was 150 ± 106 mg . While , in the sample as a whole , there was improvement in PDSS scores across the 8-week trial ( ANOVA main effect of time , F = 10.9 , df8,192 , p < 0.0001 ) , the treatment × time interaction effect was not statistically significant ( F = 0.8 , df8,192 , p = 0.61 ) . There was no between-group difference in responder frequency at endpoint . Conclusions This proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD . Quetiapine XR was generally well-tolerated . Important limitations were the small sample size , and the relatively low average dose of quetiapine XR used . Clinical Trials.gov ID # : Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam  ( n = 47 ) and paroxetine  ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P < 0.001 ) . The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies . This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder . Patients who satisfactorily completed a 12-week , double-blind , placebo-controlled study of paroxetine and clomipramine  could choose to continue receiving their r and omized treatment for a further 36 weeks . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . In total , 176 patients were included in the intention-to-treat population . The number of full panic attacks decreased in all three groups during the 12-week study , and improvements continued with long-term therapy . Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks , and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks . There were no significant differences between paroxetine and clomipramine . The proportion of patients who withdrew from the study due to adverse effects  was greater in the clomipramine group ( 19 % ) than in either the paroxetine group ( 7 % ) or the placebo group ( 9 % ) . Paroxetine was significantly more effective than placebo and as effective as ( but better tolerated than ) clomipramine in the long-term treatment of panic disorder . Not only was efficacy maintained , but continued improvement was also seen , indicating the importance of long-term treatment in patients with panic disorder Non-response to pharmacotherapy for panic disorder ( PD ) is a well-documented problem . However , little information exists to guide next-step strategies for these non-responders . In addition to pharmacologic augmentation strategies , several studies support the efficacy of cognitive-behavior therapy ( CBT ) for these patients , although data on long-term outcomes has been lacking . In this study , we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy . Sustained significant benefit was found for all dimensional outcome scores , and nearly two-thirds of the sample met remission criteria . This occurred with reductions in medication use over the follow-up period . Negative predictors of remission status included comorbid dysthymia , social phobia , and generalized anxiety disorder . These results provide additional evidence for the efficacy of CBT for medication non-responders with PD Agoraphobia in panic disorder ( PD ) has been related to abnormal balance system function . Vision influences balance and behavioural adaptations ; peripheral vision influences orienting and fast defensive reactions whereas central vision analyzes details of objects . We have hypothesized that the abnormal balance function in PD could be mainly related to peripheral vision as part of a defensive alarm system in the brain . In 25 patients with PD and agoraphobia and 31 healthy controls we assessed , by posturography ,  balance system reactivity to video-films projected in peripheral and central visual fields ( r and omized sequence ) . Length , velocity and surface of body sway were calculated . Patients increased their body sway during peripheral stimulation , whereas controls did not ; the two groups showed a similar increase of body sway during central stimulation . Anxiety levels during peripheral stimulation significantly influenced the postural response in the group of patients . These preliminary results suggest that the higher visual sensitivity to peripheral stimulation in patients with PD and agoraphobia may be linked to a more active " visual alarm system " involving visual , vestibular and limbic areas that might influence the development of agoraphobia in situations where environmental stimuli are uncertain Experimental evidence suggests that panic disorder is characterized by abnormalities in the balance system function and that these abnormalities might be related to the severity of agoraphobic avoidance . Since the balance system can be modulated by the serotonergic system , we investigated the effect of a 6‐week treatment with citalopram on the balance system function in patients with panic disorder . Fifteen patients with panic disorder with/without agoraphobia underwent static posturography on days 0 and 42 . Static posturography and clinical assessment s were carried out by different investigators who were blind to each other . Static posturography showed high percentages of abnormal scores . Patients with no or low agoraphobic avoidance showed less abnormal posturographic measures than those with moderate to severe agoraphobia . After 6 weeks of treatment with citalopram there was a significant decrease of four out of six posturography measures in eyes‐closed and neck extension conditions , whereas no significant effect was found in the eyes‐open condition . This is the first report that suggests that the modulation of the serotonergic system can improve the balance system function in patients with panic disorder , particularly when visual information is lacking . In addition , our findings confirm the observation that many patients with panic disorder have abnormalities in their balance system function , supporting the idea that these abnormalities are mainly related to agoraphobic avoidance . Depression and Anxiety 17:101–106 , 2003 . © 2003 Wiley‐Liss , INTRODUCTION Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder ( PD ) . However preliminary studies suggested that reboxetine might be effective in the treatment of PD . We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD . METHODS Sixty-eight patients with PD were assigned to treatment groups in a single-blind , r and omized design . Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Side effects were also recorded . RESULTS Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one . Vice versa we did not find any significant differences for other outcome measures . Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group . CONCLUSIONS The results showed a greater effect of paroxetine on panic attacks than reboxetine , while no differences for anticipatory anxiety and avoidance were found , suggesting a different role of noradrenaline and serotonin in the treatment of PD Abstract : The effects of short treatments ( 7 days ) with paroxetine and with reboxetine on the reactivity to inhalations of 35 % carbon dioxide (CO2)/65 % oxygen ( O2 ) were compared in 28 patients with Panic Disorder who had positive responses to 35 % CO2 inhalations . A double-blind , r and omized design was applied . Each patient was given the 35 % CO2 challenge on days 0 ( before starting the treatment ) and 7 . Anxiety reactivity to CO2 decreased significantly with both drugs but the decrease was significantly stronger in the group treated with paroxetine . The rate of patients whose reactivity has reduced of at least 50 % after 7 days was significantly higher in the group treated with paroxetine ( 10/14 , 71.5 % ) than in the one treated with reboxetine ( 3/14 , 21.5 % ) . These results indicate that the modulation of the serotonergic system is more relevant for CO2 hyperreactivity than the modulation of the noradrenergic one Previous studies indicate that serotonin reuptake inhibitors do not appear to have serious cardiac side effects . However , the effects of these agents on respiratory measures have not been studied in detail . Several studies indicate that patients with anxiety exhibit irregular breathing patterns as measured by tidal volume and respiratory rate . In this study , we evaluated the effects of a serotonin reuptake inhibitor , paroxetine , on respiratory variability in patients with panic disorder ( n = 13 ) , using linear and nonlinear measures of regularity , approximate entropy ( APEN ) and a measure of chaos , the largest Lyapunov exponent ( LLE ) , with pre- and posttreatment lung volume time series ( 256 s long sample d at 4 Hz ) . Our results show that paroxetine significantly decreases some of the linear measures of variability and supine APEN and st and ing LLE of lung volume series after successful treatment . The implication s of these findings on respiratory and cardiovascular function have been discussed The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well toler 
    Output:
    