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 : The purpose of this study was to evaluate the effect of adjunctive topiramate in treating acute mania . Methods : In this study which was a double-blinded r and omized clinical trial , 46 bipolar patients in manic episode , were treated with lithium carbonate and topiramate versus lithium carbonate and placebo and treatment responses were assessed by Young Mania Rating Scale ( YMRS ) weekly . Results : In both intervention and control groups , YMRS score had significant decline after 8 weeks(p < 0.001 ) , but there was no statistically significant difference between the two groups ( p = 0.419 ) . The highest score decline was after two weeks . YMRS score at baseline did not have statistically significant difference between the intervention and control groups ( p = 0.709 ) . Conclusions : This study failed to show antimanic efficacy of adjunctive topiramate in the treatment of those with acute manic . Declaration of interest : None . Clinical Trial Registration : URL : http://www.i rct .ir . I RCT 201110317960N1 Objective To compare the effects of topiramate versus valproate sodium as an add-on therapy to a combination of lithium and risperidone ( Li+Ris ) on body weight and serum lipid profile in children and adolescents with bipolar disorder . Methods In a single-blind r and omized clinical trial , thirty children and adolescents with bipolar disorder type I in the manic or mixed phase , treated with the combination of Li+Ris at therapeutic doses for at least 4 weeks who had the indication of add-on therapy due to a recurrent episode ; a partial response or non response in the current episode or relapse were included . Participants were r and omly assigned to receive either topiramate or sodium valproate as the third drug add-on therapy for a total of 6 weeks . Weight , height and serum lipid profiles were determined at baseline and at the end of week 6 . Results Differences in the mean levels of lipid profiles at baseline and after week 6 evaluation were not significant in both treatment groups . BMI z-score increased in both treatment groups , being significant only in the Li+Ris/Valproate group , increasing from ( mean±SD ) 0.38±0.55 to 0.72±1.23 ( p<0.05 ) . Between group changes in BMI z-score was not significant . Among the BMI percentile categories , participants in the normal weight subgroup showed a significant increase in BMI z-score during the 6 week trial , compared to overweight/obese subgroup , in both Li+Ris/Valproate and Li+Ris/Topiramate treatment groups . Elevated mean serum level of triglyceride and a high proportion of participants with elevated total cholesterol ( ≥ 170 mg/dl ) , triglyceride ( ≥ 110 mg/dl ) , and BMI percentile 85-<95 at baseline ( before r and omization ) and at the end of 6 week study were noted . Conclusion When topiramate and valproate sodium are used for six weeks as adjunctive treatment to a combination of Li+Ris , they act alike on lipid milieu of children and adolescents with bipolar disorder . Both Li+Ris/Valproate and Li+Ris/Topiramate therapies can lead to an increase in BMI z-score . This increase is statistically significant with Li+Ris/Valproate therapy . This suggests that topiramate could attenuate the ongoing weight  gain from lithium and risperidone . In this study , the majority of participants who gained weight were those with BMI less than 85th percentile . This suggests that normal weight patients may have greater weight gain potential than overweight/obese patients .High proportion of metabolic abnormalities among the patients at baseline , which remained elevated throughout the trial , warrants cardiometabolic monitoring in this population OBJECTIVE Antiepileptic drugs ( AEDs ) are commonly employed in the treatment of bipolar disorder . The efficacy and tolerability of topiramate , a novel anticonvulsant , and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions ( rater-blinded ) in patients meeting DSM-IV criteria for bipolar I/II depression . METHODS A total of 36 out- patients with Hamilton Depression Rating Scale ( HDRS-17 ) scores > or = 16 were r and omized to receive escalating doses of either topiramate ( 50 - 300 mg/day ) or bupropion SR ( 100 - 400 mg/day ) for 8 weeks . Data were analyzed on an intent-to-treat basis using the last observation carried forward method . RESULTS The percentage of patients meeting a priori response criteria ( > or = 50 % decrease from baseline in mean HDRS-17 total score ) was significant for both topiramate ( 56 % ) and bupropion SR ( 59 % ) [ t(17 ) = 2.542 , p = 0.04 and t(17 ) = 2.661 , p = 0.03 , respectively ] . Baseline demographic and clinical parameters were comparable between the two treatment groups . The mean doses of study medication were 176 mg/day ( SD = 102 mg/day ) for the topiramate-treated group and 250 mg/day ( SD = 133 mg/day ) for the bupropion SR-treated group . A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment , according to a > or = 50 % reduction in the HDRS-17 . Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups ( p = 0.001 ) , however , differences between the topiramate-treated group and the bupropion SR-treated group were not significant [ t(36 ) = 1.754 , p = 0.097 ] . Both topiramate and bupropion SR were generally well tolerated .  Thirteen patients discontinued the study : 2 because of lack of efficacy  , 1 due to withdrawal of consent and 10 following side-effects ( six in the topiramate and four in the bupropion SR-treated group ) . There were no cases of affective switch in either arm . Weight loss was experienced by patients in both groups ( mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate ) [ t(17 ) = 2.325 , p = 0.061 and t(17 ) = 2.481 , p = 0.043 , respectively ] . CONCLUSIONS These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression . The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation BACKGROUND To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder , we evaluated the response of 56 bipolar out patients in the Stanley Foundation Bipolar Outcome Network ( SFBN ) who had been treated with adjunctive topiramate in an open-label , naturalistic fashion . METHODS In this case series , response to topiramate was assessed every 2 weeks for the first 3 months according to st and ard ratings in the SFBN , and monthly thereafter while patients remained on topiramate .  Patients ' weights , body mass indices ( BMI s ) , and side effects were also assessed . RESULTS Of the 54 patients who completed at least 2 weeks of open-label , add-on topiramate  treatment , 30 had manic , mixed , or cycling symptoms , 11 had depressed symptoms , and 13 were relatively euthymic at the time topiramate was begun . Patients who had been initially treated for manic symptoms displayed significant reductions in st and ard ratings scores after 4 weeks , after 10 weeks , and at the last evaluation . Those patients who were initially depressed or treated while euthymic showed no significant changes . Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4 , to week 10 , and to the last evaluation . The most common adverse side effects were neurologic and gastrointestinal . CONCLUSIONS These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder , and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician . Controlled studies of topiramate 's acute and long-term efficacy and side effects in bipolar disorder appear warranted Objective : To assess open-label adjunctive topiramate in the treatment of out patients with unstable bipolar disorder ( BD ) . Method : Out patients with DSM-IV – defined BD ( I or II ) exhibiting mood instability were enrolled in this 16-week , open-label , multicentre study . Topiramate was added to existing mood stabilizers and other psychotropic treatments . The primary effectiveness measure was the Clinical Global Impression of Severity ( CGI-S ) scale ; other scales included the Young Mania Rating Scale ( YMRS ) and the Montgomery – Asberg Depression Rating Scale ( MADRS ) . Safety assessment s included monitoring adverse events , measuring tremor , monitoring vital signs and weight , and laboratory indices . We also evaluated patient satisfaction with treatment . Results : A total of 109 patients were enrolled . Intent-to-treat analysis showed significant improvement from baseline in the CGI-S , YMRS , and MADRS , starting at Week 2 ( P < 0.001 ) , with further accrual of benefit between Week 2 and Week 16 ( P < 0.001 ) . The mean modal dosage of topiramate during the stable dosing period was 180 mg daily . There was a mean 1.8 kg decrease in patient weight  from topiramate initiation to Week 16 ( P < 0.001 ) . Topiramate was well tolerated by most patients ; 11 % withdrew from the study owing to adverse events . We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment ( P < 0.005 ) ; no notable changes in vital signs were observed . At Week 16 , 50 % of the patients were “ completely satisfied ” with topiramate treatment . Conclusions : Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms , as well as reducing tremor and weight in out patients with BD I or II RATIONALE Because some anti-epileptic drugs ( AEDs ) are effective in bipolar affective disorders , the new AED topiramate ( TPM ) may be effective in psychiatric illnesses . TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs . METHODS Charts of 58 consecutive patients , 39 out patients ( 15 males , 24 females ) and 19 in patients ( 6 males , 13 females ) were review ed .  TPM 25 mg . b.i.d . was added to existing therapy and titrated in 50 mg increments every 3 - 7 days . Improvement was rated on a Likert global assessment scale of marked , moderate , mild , or no improvement or worse , based on quality of sleep , appetite , mood , and concentration . RESULTS Of the 58 patients with psychiatric disorders , 44 patients had rapid cycling bipolar disorders characterized by manic , hypomanic , or mixed episodes . Eighteen patients had previously failed to respond to lamotrigine and /or gabapentin in addition to conventional mood stabilizers . Fourteen were Bipolar I , six Bipolar II , and seven mixed , ten patients had cyclothymic disorder , seven had bipolar disorder not otherwise specified . Of the remaining 14 patients , nine had schizoaffective disorder , three patients had dementia and two had psychosis . Mean duration of TPM treatment was 16.0 weeks ; mean TPM dosage approximately 200 mg/day . Thirty-six of 58 ( 62 % ) patients exhibited marked or moderate improvement , usually within days or weeks . Twenty-three of 44 ( 52 % ) patients with bipolar affective disorders showed marked or moderate improvement . Minimal/no improvement was observed in 16 ; six were rated as worse . Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM ( 800 mg ) and tranylcypromine sulfate ( 170 mg ) combined with alcohol . Other adverse effects were minor and included : paresthesias , somnolence , fatigue , impaired concentration and memory , nausea , and diarrhoea . LIMITATIONS This study was performed in a nonr and om open and retrospective fashion . Therefore , any findings are limited by the design of this study . CONCLUSION TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation OBJECTIVE To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD This double-blind , placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy . Efficacy end points included the Young Mania Rating Scale ( YMRS ) , Brief Psychiatric Rating Scale for Children , Children 's Depression Rating Scale , Children 's Global Assessment Scale , and Clinical Global Impressions-Improvement . RESULTS Fifty-six children and adolescents ( 6 - 17 years ) with a diagnosis of bipolar disorder type I received topiramate ( 
    Output:
    
agent
It is not possible to draw any firm conclusions about the use of topiramate in clinical practice from this evidence .
***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 : The purpose of this study was to evaluate the effect of adjunctive topiramate in treating acute mania . Methods : In this study which was a double-blinded r and omized clinical trial , 46 bipolar patients in manic episode , were treated with lithium carbonate and topiramate versus lithium carbonate and placebo and treatment responses were assessed by Young Mania Rating Scale ( YMRS ) weekly . Results : In both intervention and control groups , YMRS score had significant decline after 8 weeks(p < 0.001 ) , but there was no statistically significant difference between the two groups ( p = 0.419 ) . The highest score decline was after two weeks . YMRS score at baseline did not have statistically significant difference between the intervention and control groups ( p = 0.709 ) . Conclusions : This study failed to show antimanic efficacy of adjunctive topiramate in the treatment of those with acute manic . Declaration of interest : None . Clinical Trial Registration : URL : http://www.i rct .ir . I RCT 201110317960N1 Objective To compare the effects of topiramate versus valproate sodium as an add-on therapy to a combination of lithium and risperidone ( Li+Ris ) on body weight and serum lipid profile in children and adolescents with bipolar disorder . Methods In a single-blind r and omized clinical trial , thirty children and adolescents with bipolar disorder type I in the manic or mixed phase , treated with the combination of Li+Ris at therapeutic doses for at least 4 weeks who had the indication of add-on therapy due to a recurrent episode ; a partial response or non response in the current episode or relapse were included . Participants were r and omly assigned to receive either topiramate or sodium valproate as the third drug add-on therapy for a total of 6 weeks . Weight , height and serum lipid profiles were determined at baseline and at the end of week 6 . Results Differences in the mean levels of lipid profiles at baseline and after week 6 evaluation were not significant in both treatment groups . BMI z-score increased in both treatment groups , being significant only in the Li+Ris/Valproate group , increasing from ( mean±SD ) 0.38±0.55 to 0.72±1.23 ( p<0.05 ) . Between group changes in BMI z-score was not significant . Among the BMI percentile categories , participants in the normal weight subgroup showed a significant increase in BMI z-score during the 6 week trial , compared to overweight/obese subgroup , in both Li+Ris/Valproate and Li+Ris/Topiramate treatment groups . Elevated mean serum level of triglyceride and a high proportion of participants with elevated total cholesterol ( ≥ 170 mg/dl ) , triglyceride ( ≥ 110 mg/dl ) , and BMI percentile 85-<95 at baseline ( before r and omization ) and at the end of 6 week study were noted . Conclusion When topiramate and valproate sodium are used for six weeks as adjunctive treatment to a combination of Li+Ris , they act alike on lipid milieu of children and adolescents with bipolar disorder . Both Li+Ris/Valproate and Li+Ris/Topiramate therapies can lead to an increase in BMI z-score . This increase is statistically significant with Li+Ris/Valproate therapy . This suggests that topiramate could attenuate the ongoing weight  gain from lithium and risperidone . In this study , the majority of participants who gained weight were those with BMI less than 85th percentile . This suggests that normal weight patients may have greater weight gain potential than overweight/obese patients .High proportion of metabolic abnormalities among the patients at baseline , which remained elevated throughout the trial , warrants cardiometabolic monitoring in this population OBJECTIVE Antiepileptic drugs ( AEDs ) are commonly employed in the treatment of bipolar disorder . The efficacy and tolerability of topiramate , a novel anticonvulsant , and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions ( rater-blinded ) in patients meeting DSM-IV criteria for bipolar I/II depression . METHODS A total of 36 out- patients with Hamilton Depression Rating Scale ( HDRS-17 ) scores > or = 16 were r and omized to receive escalating doses of either topiramate ( 50 - 300 mg/day ) or bupropion SR ( 100 - 400 mg/day ) for 8 weeks . Data were analyzed on an intent-to-treat basis using the last observation carried forward method . RESULTS The percentage of patients meeting a priori response criteria ( > or = 50 % decrease from baseline in mean HDRS-17 total score ) was significant for both topiramate ( 56 % ) and bupropion SR ( 59 % ) [ t(17 ) = 2.542 , p = 0.04 and t(17 ) = 2.661 , p = 0.03 , respectively ] . Baseline demographic and clinical parameters were comparable between the two treatment groups . The mean doses of study medication were 176 mg/day ( SD = 102 mg/day ) for the topiramate-treated group and 250 mg/day ( SD = 133 mg/day ) for the bupropion SR-treated group . A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment , according to a > or = 50 % reduction in the HDRS-17 . Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups ( p = 0.001 ) , however , differences between the topiramate-treated group and the bupropion SR-treated group were not significant [ t(36 ) = 1.754 , p = 0.097 ] . Both topiramate and bupropion SR were generally well tolerated .  Thirteen patients discontinued the study : 2 because of lack of efficacy  , 1 due to withdrawal of consent and 10 following side-effects ( six in the topiramate and four in the bupropion SR-treated group ) . There were no cases of affective switch in either arm . Weight loss was experienced by patients in both groups ( mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate ) [ t(17 ) = 2.325 , p = 0.061 and t(17 ) = 2.481 , p = 0.043 , respectively ] . CONCLUSIONS These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression . The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation BACKGROUND To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder , we evaluated the response of 56 bipolar out patients in the Stanley Foundation Bipolar Outcome Network ( SFBN ) who had been treated with adjunctive topiramate in an open-label , naturalistic fashion . METHODS In this case series , response to topiramate was assessed every 2 weeks for the first 3 months according to st and ard ratings in the SFBN , and monthly thereafter while patients remained on topiramate .  Patients ' weights , body mass indices ( BMI s ) , and side effects were also assessed . RESULTS Of the 54 patients who completed at least 2 weeks of open-label , add-on topiramate  treatment , 30 had manic , mixed , or cycling symptoms , 11 had depressed symptoms , and 13 were relatively euthymic at the time topiramate was begun . Patients who had been initially treated for manic symptoms displayed significant reductions in st and ard ratings scores after 4 weeks , after 10 weeks , and at the last evaluation . Those patients who were initially depressed or treated while euthymic showed no significant changes . Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4 , to week 10 , and to the last evaluation . The most common adverse side effects were neurologic and gastrointestinal . CONCLUSIONS These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder , and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician . Controlled studies of topiramate 's acute and long-term efficacy and side effects in bipolar disorder appear warranted Objective : To assess open-label adjunctive topiramate in the treatment of out patients with unstable bipolar disorder ( BD ) . Method : Out patients with DSM-IV – defined BD ( I or II ) exhibiting mood instability were enrolled in this 16-week , open-label , multicentre study . Topiramate was added to existing mood stabilizers and other psychotropic treatments . The primary effectiveness measure was the Clinical Global Impression of Severity ( CGI-S ) scale ; other scales included the Young Mania Rating Scale ( YMRS ) and the Montgomery – Asberg Depression Rating Scale ( MADRS ) . Safety assessment s included monitoring adverse events , measuring tremor , monitoring vital signs and weight , and laboratory indices . We also evaluated patient satisfaction with treatment . Results : A total of 109 patients were enrolled . Intent-to-treat analysis showed significant improvement from baseline in the CGI-S , YMRS , and MADRS , starting at Week 2 ( P < 0.001 ) , with further accrual of benefit between Week 2 and Week 16 ( P < 0.001 ) . The mean modal dosage of topiramate during the stable dosing period was 180 mg daily . There was a mean 1.8 kg decrease in patient weight  from topiramate initiation to Week 16 ( P < 0.001 ) . Topiramate was well tolerated by most patients ; 11 % withdrew from the study owing to adverse events . We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment ( P < 0.005 ) ; no notable changes in vital signs were observed . At Week 16 , 50 % of the patients were “ completely satisfied ” with topiramate treatment . Conclusions : Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms , as well as reducing tremor and weight in out patients with BD I or II RATIONALE Because some anti-epileptic drugs ( AEDs ) are effective in bipolar affective disorders , the new AED topiramate ( TPM ) may be effective in psychiatric illnesses . TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs . METHODS Charts of 58 consecutive patients , 39 out patients ( 15 males , 24 females ) and 19 in patients ( 6 males , 13 females ) were review ed .  TPM 25 mg . b.i.d . was added to existing therapy and titrated in 50 mg increments every 3 - 7 days . Improvement was rated on a Likert global assessment scale of marked , moderate , mild , or no improvement or worse , based on quality of sleep , appetite , mood , and concentration . RESULTS Of the 58 patients with psychiatric disorders , 44 patients had rapid cycling bipolar disorders characterized by manic , hypomanic , or mixed episodes . Eighteen patients had previously failed to respond to lamotrigine and /or gabapentin in addition to conventional mood stabilizers . Fourteen were Bipolar I , six Bipolar II , and seven mixed , ten patients had cyclothymic disorder , seven had bipolar disorder not otherwise specified . Of the remaining 14 patients , nine had schizoaffective disorder , three patients had dementia and two had psychosis . Mean duration of TPM treatment was 16.0 weeks ; mean TPM dosage approximately 200 mg/day . Thirty-six of 58 ( 62 % ) patients exhibited marked or moderate improvement , usually within days or weeks . Twenty-three of 44 ( 52 % ) patients with bipolar affective disorders showed marked or moderate improvement . Minimal/no improvement was observed in 16 ; six were rated as worse . Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM ( 800 mg ) and tranylcypromine sulfate ( 170 mg ) combined with alcohol . Other adverse effects were minor and included : paresthesias , somnolence , fatigue , impaired concentration and memory , nausea , and diarrhoea . LIMITATIONS This study was performed in a nonr and om open and retrospective fashion . Therefore , any findings are limited by the design of this study . CONCLUSION TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation OBJECTIVE To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD This double-blind , placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy . Efficacy end points included the Young Mania Rating Scale ( YMRS ) , Brief Psychiatric Rating Scale for Children , Children 's Depression Rating Scale , Children 's Global Assessment Scale , and Clinical Global Impressions-Improvement . RESULTS Fifty-six children and adolescents ( 6 - 17 years ) with a diagnosis of bipolar disorder type I received topiramate ( 
    Output:
    