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: Few r and omized controlled trials have included panic disorder patients with moderate to severe agoraphobia . Therefore , this population was studied using pharmacotherapy as well as psychotherapy . At the time of the study , imipramine was widely used as a pharmacological treatment . Also , current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy . Therefore , the main objective of this study is to compare four psychosocial treatments — cognitive and grade d in vivo exposure treatments , grade d in vivo exposure , cognitive treatment , and supportive therapy — to evaluate the benefits of combining cognitive therapy with exposure in vivo . These treatments were combined with imipramine or placebo for a total of eight experimental conditions . Participants presented moderate to severe agoraphobia . The method involved a r and omized , double‐blind , placebo‐controlled trial with 137 participants who completed a 14‐session protocol involving the treatments just mentioned . Measures were taken at baseline and posttreatment and at 3‐ , 6‐ , and 12‐month follow‐up . All treatment conditions were statistically and clinical ly effective in reducing self‐reported panic – agoraphobia symptoms over the 1‐year follow‐up . No statistical differences were observed between imipramine and placebo conditions . This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1‐year follow‐up period . These surprising results support the need to document the relations among the various components of an intervention . This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole BACKGROUND Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities . However , some disorders , particularly the anxiety-related disorders exemplified by specific phobia , have an emotional learning component to them that can be facilitated with psychotherapy . OBJECTIVE To determine whether D-cycloserine ( DCS ) , a partial agonist at the N-methyl-d-aspartate receptor that has previously been shown to improve extinction of fear in rodents , will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy . DESIGN R and omized , double-blind , placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm . SETTING Participants were recruited from the general community to a research clinic . PARTICIPANTS Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview for DSM-IV were enrolled . INTERVENTIONS After we obtained pretreatment measures of fear , subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator . Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy . Subjects , therapists , and assessors were blind to the treatment condition . Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms . MAIN OUTCOME MEASURES Included were measures of acrophobia within the virtual environment , measures of acrophobia in the real world , and general measures of overall improvement . An objective measure of fear , electrodermal skin fluctuation , was also included during the virtual exposure to heights . Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment . RESULTS Exposure therapy combined with DCS result ed in significantly larger reductions of acrophobia symptoms on all main outcome measures . Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment ( 1 week after treatment , P</=.001 ; 3 months later , P</=.05 ) . Subjects receiving DCS also showed significantly greater decreases in posttreatment skin conductance fluctuations during the virtual exposure ( P</=.05 ) . Additionally , subjects receiving DCS had significantly greater improvement compared with subjects receiving placebo on general measures of real-world acrophobia symptoms ( acrophobia avoidance [ P</=.02 ] , acrophobia anxiety [ P</=.01 ] , attitudes toward heights [ P</=.04 ] , clinical global improvement [ P</=.01 ] , and number of self-exposures to real-world heights [ P</=.01 ] ) ; the improvement was evident early in treatment and was maintained at 3 months . CONCLUSION These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology In spite of excessive fear during a panic attack , studies have found no or little evidence for an activation of cortisol during natural panic attacks . Whether this phenomenon is related to psychopathology or outcome of psychotherapy is unknown . In this study , 10 patients with panic disorder and agoraphobia were treated with cognitive behavioural therapy including 3 in-vivo exposures ( flooding ) to individual phobic situations . Before , during and after exposure , the level of subjective fear was assessed and blood was collected simultaneously . Cortisol and ACTH were analysed from plasma . Ten matched healthy control subjects went through the same procedure . Fear and stress hormones during exposure were compared in patients and controls as well as related to therapy outcome at the end of therapy and 2 follow-ups in patients . Results showed that the concentrations of cortisol and ACTH did not significantly increase during exposure . Patients ' cortisol concentrations were higher than those of controls at baseline and during exposure , while ACTH concentrations were comparable before and during exposure , and even lower than those of controls at recovery . Cortisol concentrations were moderately but consistently correlated to therapy outcome , i.e. patients with least cortisol release during exposure profited least from therapy . The study showed that a lack of stimulation of the HPA system at repeated confrontation with the phobic situation was related to therapeutic outcome . Mechanisms of action via the influence of cortisol on extinction learning or the inhibition of central excitatory neurotransmission are conceivable BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p < /=.05 ) , as measured by the Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder CONTEXT This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam , a benzodiazepine . OBJECTIVES To evaluate the clinical efficacy of clonazepam in a fixed dosage ( 2 mg/day ) , compared to placebo , in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes . TYPE OF STUDY R and omized study with clonazepam and placebo . SETTING Outpatient Anxiety and Depression Unit of the Institute of Psychiatry , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil . PARTICIPANTS 34 patients with a diagnosis of panic disorder with agoraphobia , between 18 and 55 years old . PROCEDURES Administration of clonazepam or placebo for 6 weeks , in panic disorder patients , after they were classified within two subtypes of panic disorder : respiratory and non-respiratory . MAIN MEASUREMENTS Changes in the number of panic attacks in comparison with the period before the beginning of the study ; Hamilton Anxiety Scale ; Global Clinical Impression Scale ; and Patient 's Global Impression scale . RESULTS In the group that received clonazepam , by the end of the 6th week there was a statistically significant clinical improvement , shown by the remission of panic attacks ( p < 0.001 ) and decrease in anxiety ( p = 0.024 ) . In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder , regarding the therapeutic response to clonazepam . CONCLUSION Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder , suggesting there is no difference in the therapeutic response between the two subtypes 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 BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients 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 agoraphob 
    Output:
    
agent
Paroxetine , sertraline , citalopram , escitalopram , and clomipramine showed the most consistent results , while fluvoxamine , fluoxetine , and imipramine showed limited efficacy .
Preliminary results suggested the potential efficacy of inositol ; D-cycloserine showed mixed results for its ability to improve the outcome of exposure-based cognitive behavioral therapy .
No studies have been specifically oriented toward evaluating the effect of drugs on AG ; in the available studies , the improvement of AG might have been the consequence of the reduction of panic attacks .
***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: Few r and omized controlled trials have included panic disorder patients with moderate to severe agoraphobia . Therefore , this population was studied using pharmacotherapy as well as psychotherapy . At the time of the study , imipramine was widely used as a pharmacological treatment . Also , current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy . Therefore , the main objective of this study is to compare four psychosocial treatments — cognitive and grade d in vivo exposure treatments , grade d in vivo exposure , cognitive treatment , and supportive therapy — to evaluate the benefits of combining cognitive therapy with exposure in vivo . These treatments were combined with imipramine or placebo for a total of eight experimental conditions . Participants presented moderate to severe agoraphobia . The method involved a r and omized , double‐blind , placebo‐controlled trial with 137 participants who completed a 14‐session protocol involving the treatments just mentioned . Measures were taken at baseline and posttreatment and at 3‐ , 6‐ , and 12‐month follow‐up . All treatment conditions were statistically and clinical ly effective in reducing self‐reported panic – agoraphobia symptoms over the 1‐year follow‐up . No statistical differences were observed between imipramine and placebo conditions . This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1‐year follow‐up period . These surprising results support the need to document the relations among the various components of an intervention . This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole BACKGROUND Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities . However , some disorders , particularly the anxiety-related disorders exemplified by specific phobia , have an emotional learning component to them that can be facilitated with psychotherapy . OBJECTIVE To determine whether D-cycloserine ( DCS ) , a partial agonist at the N-methyl-d-aspartate receptor that has previously been shown to improve extinction of fear in rodents , will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy . DESIGN R and omized , double-blind , placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm . SETTING Participants were recruited from the general community to a research clinic . PARTICIPANTS Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview for DSM-IV were enrolled . INTERVENTIONS After we obtained pretreatment measures of fear , subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator . Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy . Subjects , therapists , and assessors were blind to the treatment condition . Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms . MAIN OUTCOME MEASURES Included were measures of acrophobia within the virtual environment , measures of acrophobia in the real world , and general measures of overall improvement . An objective measure of fear , electrodermal skin fluctuation , was also included during the virtual exposure to heights . Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment . RESULTS Exposure therapy combined with DCS result ed in significantly larger reductions of acrophobia symptoms on all main outcome measures . Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment ( 1 week after treatment , P</=.001 ; 3 months later , P</=.05 ) . Subjects receiving DCS also showed significantly greater decreases in posttreatment skin conductance fluctuations during the virtual exposure ( P</=.05 ) . Additionally , subjects receiving DCS had significantly greater improvement compared with subjects receiving placebo on general measures of real-world acrophobia symptoms ( acrophobia avoidance [ P</=.02 ] , acrophobia anxiety [ P</=.01 ] , attitudes toward heights [ P</=.04 ] , clinical global improvement [ P</=.01 ] , and number of self-exposures to real-world heights [ P</=.01 ] ) ; the improvement was evident early in treatment and was maintained at 3 months . CONCLUSION These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology In spite of excessive fear during a panic attack , studies have found no or little evidence for an activation of cortisol during natural panic attacks . Whether this phenomenon is related to psychopathology or outcome of psychotherapy is unknown . In this study , 10 patients with panic disorder and agoraphobia were treated with cognitive behavioural therapy including 3 in-vivo exposures ( flooding ) to individual phobic situations . Before , during and after exposure , the level of subjective fear was assessed and blood was collected simultaneously . Cortisol and ACTH were analysed from plasma . Ten matched healthy control subjects went through the same procedure . Fear and stress hormones during exposure were compared in patients and controls as well as related to therapy outcome at the end of therapy and 2 follow-ups in patients . Results showed that the concentrations of cortisol and ACTH did not significantly increase during exposure . Patients ' cortisol concentrations were higher than those of controls at baseline and during exposure , while ACTH concentrations were comparable before and during exposure , and even lower than those of controls at recovery . Cortisol concentrations were moderately but consistently correlated to therapy outcome , i.e. patients with least cortisol release during exposure profited least from therapy . The study showed that a lack of stimulation of the HPA system at repeated confrontation with the phobic situation was related to therapeutic outcome . Mechanisms of action via the influence of cortisol on extinction learning or the inhibition of central excitatory neurotransmission are conceivable BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p < /=.05 ) , as measured by the Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder CONTEXT This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam , a benzodiazepine . OBJECTIVES To evaluate the clinical efficacy of clonazepam in a fixed dosage ( 2 mg/day ) , compared to placebo , in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes . TYPE OF STUDY R and omized study with clonazepam and placebo . SETTING Outpatient Anxiety and Depression Unit of the Institute of Psychiatry , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil . PARTICIPANTS 34 patients with a diagnosis of panic disorder with agoraphobia , between 18 and 55 years old . PROCEDURES Administration of clonazepam or placebo for 6 weeks , in panic disorder patients , after they were classified within two subtypes of panic disorder : respiratory and non-respiratory . MAIN MEASUREMENTS Changes in the number of panic attacks in comparison with the period before the beginning of the study ; Hamilton Anxiety Scale ; Global Clinical Impression Scale ; and Patient 's Global Impression scale . RESULTS In the group that received clonazepam , by the end of the 6th week there was a statistically significant clinical improvement , shown by the remission of panic attacks ( p < 0.001 ) and decrease in anxiety ( p = 0.024 ) . In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder , regarding the therapeutic response to clonazepam . CONCLUSION Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder , suggesting there is no difference in the therapeutic response between the two subtypes 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 BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients 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 agoraphob 
    Output:
    