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 aim of this study was to study valproate  efficacy and safety for aggression in children and adolescents with pervasive developmental disorders ( PDD ) . METHODS In this prospect i ve double-blind , placebo-controlled study , 30 subjects ( 20 boys , 10 girls ) 6 - 20 years of age with PDD and significant aggression were r and omized and received treatment with valproate ( VPA ) or placebo ( PBO ) for 8 weeks as out patients . Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8 . RESULTS No treatment difference was observed statistically between VPA and PBO groups . The Aberrant Behavior Checklist -- Community Scale ( ABC-C ) Irritability subscale was the primary outcome measure ( p = 0.65 ) , and CGI -- Improvement ( p = 0.16 ) and OAS ( p = 0.96 ) were secondary outcome measures . Increased appetite and skin rash were significant side effects . Only 1 subject was dropped from the study owing to side effects , notably a spreading skin rash , which then resolved spontaneously . Two subjects receiving VPA developed increased serum ammonia levels , one with an associated parent report of slurred speech and mild cognitive slowing . Post study , of 16 VPA and PBO subjects receiving VPA , 10 subjects demonstrated sustained response , 4 of whom later attempted taper , with significant relapse of aggression . CONCLUSION The present negative findings can not be viewed as conclusive , partly owing to the large placebo response , subject heterogeneity , and size of the groups . Larger studies are needed to exp and upon these findings OBJECTIVE To compare the efficacy and safety of divalproex extended-release ( ER ) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study . METHOD In the double-blind study , 150 patients ( manic or mixed episode , aged 10 - 17 years ) with baseline Young Mania Rating Scale ( YMRS ) score of 20 or higher were r and omized to once-daily placebo or divalproex ER , which was titrated to clinical response or serum valproate concentration of 80 to 125 microg/mL. Sixty-six patients enrolled in the extension study . RESULTS In the double-blind study , a treatment effect was not observed with divalproex ER based on change in mean YMRS score  ( divalproex ER -8.8 [ n = 74 ] ; placebo -7.9 [ n = 70 ] ) or secondary measures . Divalproex was similar to placebo based on incidence of adverse events . Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events . Mean ammonia levels increased in the divalproex ER group , but only one patient was symptomatic . In the long-term study , YMRS scores decreased modestly ( 2.2 points from baseline ) . The most common adverse events were headache and vomiting . CONCLUSIONS The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder , mixed or manic state . Further controlled trials are required to confirm or refute the findings from this study OBJECTIVE This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents . METHOD A total of 116 out patients 7 to 18 years of age with bipolar I disorder , manic or mixed , were recruited at 20 centers in the United States and r and omly assigned to receive 7 weeks of double-blinded , flexibly dosed treatment with oxcarbazepine ( maximum dose 900 - 2400 mg/day ) or placebo . The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale ( YMRS ) , using the last-observation-carried-forward method . RESULTS Oxcarbazepine ( mean dose=1515 mg/day ) did not significantly improve YMRS scores at endpoint compared with placebo [ adjusted mean change : oxcarbazepine , -10.90 ( N=55 ) ; placebo , -9.79 ( N=55 ) ] . Dizziness , nausea , somnolence , diplopia , fatigue , and rash were each reported in at least 5 % of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group . The majority of adverse events were mild to moderate and occurred during the titration period . Eleven patients ( 19 % ) in the oxcarbazepine group discontinued the study because of adverse events , compared with two ( 4 % ) in the placebo group . CONCLUSIONS Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths . While the overall adverse event profile was similar to that reported for patients with epilepsy , the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population OBJECTIVE The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children , 3 - 7 years of age , with bipolar I disorder ( BPD ) , during a mixed or manic episode . METHODS Forty-six children with Diagnostic and Statistical Manual of Mental Disorders . 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of bipolar disorder , manic , hypomanic , or mixed episode , were recruited over a 6 year period from two academic outpatient programs for a double-blinded , placebo-controlled trial in which subjects were r and omized in a 2:2:1 ratio to risperidone solution , valproic acid , or placebo . RESULTS After 6 weeks of treatment , the least-mean Young Mania Rating Scale ( YMRS ) total scores change , adjusted for baseline YMRS scores , from baseline by treatment group was : Valproic acid 10.0±2.46 ( p=0.50 ) ; risperidone 18.82±1.55 ( p=0.008 ) ; and placebo 4.29±3.56 ( F=3.93 , p=0.02 ) . The mixed models for repeated measure ( MMRM ) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects ( p=0.008 ) but not for valproic acid-treated subjects versus placebo-treated subjects ( p=0.50 ) . Treatment with risperidone over 6 weeks led to increased prolactin levels , liver functions , metabolic measures , and weight/body mass index ( BMI ) . Treatment with valproic acid led to increases in weight/ BMI and decreases in total red blood cells ( RBC ) , hemoglobin , and hematocrit . CONCLUSIONS In this small sample of preschool children with BPD  , risperidone demonstrated clear efficacy versus placebo , whereas valproic acid did not . The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics , and that , therefore , frequent laboratory and weight monitoring are warranted OBJECTIVE To determine whether divalproex sodium ( DVPX ) was superior to lithium carbonate ( Li+ ) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX ( Li+/DVPX ) pharmacotherapy . METHOD Youths ages 5 - 17 years with bipolar I or II disorder were initially treated with Li /DVPX . Patients meeting remission criteria for four consecutive weeks were then r and omized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks . Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures . RESULTS Patients were recruited between July 1998 and May 2002 . One hundred thirty-nine youths with a mean ( SD ) age of 10.8 ( 3.5 ) years were initially treated with Li+/DVPX for a mean ( SD ) duration of 10.7 ( 5.4 ) weeks . Sixty youths were then r and omized to receive monotherapy with Li+ ( n = 30 ) or DVPX ( n = 30 ) . The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse ( p = .55 ) or survival time until discontinuation for any reason ( p = .72 ) . CONCLUSIONS DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy OBJECTIVE There is evidence for the efficacy and safety of clonazepam ( CZP ) in adult anxiety disorders , but no formal studies to substantiate clinical reports of similar benefit in children with anxiety disorders . METHOD In this double-blind pilot study , 15 children , aged 7 to 13 years , entered a r and omly assigned , double-blind crossover trial of 4 weeks of CZP ( up to 2 mg/day ) and 4 weeks of placebo . RESULTS Twelve children completed the trial . All but 1 had a diagnosis of separation anxiety disorder , and all but 2 had comorbid diagnoses . Nine children appeared to have moderate to significant clinical improvement , but statistical comparisons on several ratings failed to confirm a trend in favor of CZP . Side effects of drowsiness , irritability , and /or oppositional behavior were notable in 10 children in the CZP phase compared with 5 in the placebo phase . CONCLUSIONS Clonazepam was believed to have clinical benefit for some children , but this was not confirmed statistically in this small sample . Problematic side effects of drowsiness and disinhibition were common and possibly were due to rapid titration The objective of this study was to investigate the effectiveness of levetiracetam for the treatment of  tics in children with Tourette syndrome ( TS ) .  Levetiracetam , an atypical anticonvulsant , has been suggested in open-label protocol s to be an effective tic-suppressing agent in individuals with TS . A double blind , r and omized , placebo-controlled , cross-over trial was performed to investigate this medication in children with moderate to moderately-severe tics . Subjects received , in a r and omized sequence , 4-weeks of levetiracetam ( maximum dose 30 mg/kg/day ) or placebo , with a 2-week intervening washout period between cycles . Primary outcome measures included two separate scales from the Yale Global Tic Severity Scale ; the Total Tic score and the Total overall score . Measures were assessed at baseline , prior to r and omization , on Day 28 ( end of Phase 1 ) , on Day 42 ( baseline for second phase ) and on Day 70 ( end of Phase 2 ) . Twenty-two subjects ( 21 boys and 1 girl ) with TS , mean age 12.2 + /- 2.3 years , range 8 to 16 years , participated . A mild reduction in tics occurred during both the levetiracetam and placebo treatment phases . There was no significant difference between treatments and no evidence of sequence or cross-over effects . In conclusion , Levetiracetam is not more beneficial than placebo in suppressing tics in children with TS OBJECTIVE The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium . METHOD Twenty outpatient children and adolescents ( ages 10 - 18 ) with a disruptive behavior disorder ( oppositional defiant disorder or conduct disorder ) met the specific criteria for explosive temper and mood lability . They received 6 weeks of divalproex treatment and 6 weeks of placebo by r and om assignment . Independent evaluators blind to group assignment assessed response at the end of each phase . RESULTS At the end of phase 1 , eight of 10 subjects had responded to divalproex ; zero of 10 had responded to placebo . Of the 15 subjects who completed both phases , 12 has superior response taking divalproex . CONCLUSIONS This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents BACKGROUND New treatments for conduct disorder are sorely needed . We aim ed to test the efficacy of divalproex sodium for the treatment of conduct disorder . METHOD Seventy-one youths with conduct disorder according to DSM-IV criteria were enrolled in a r and omized , controlled , 7-week clinical trial . Subjects were all adolescent males with at least 1 crime conviction . Subjects were r and omized into high- and low-dose conditions and were openly managed by a clinical team . Subjects and independent outcome raters were blinded to condition . Clinical Global Impressions-Severity of Illness ( CGI-S ) and CGI-Improvement ( CGI-I ) ratings , Weinberger Adjustment Inventory ratings , and staff ratings of behavioral privilege were used to assess outcome . RESULTS Intent-to-treat analyses showed significant associations between assignment to the high-dose condition and ratings on the CGI-S ( p = .02 ) and CGI-I ( p = .0008 ) . Self-reported weekly impulse control was significantly better in the high-dose condition ( p < .05 ) , and association between improvement in self-restraint and treatment condition was of borderline statistical significance ( p < .06 ) . Parallel analyses comparing outcome by blood drug level achieved strengthened the results , as expected . 
    Output:
    
agent
In several small , single-site RCTs , valproate and sulthiame were better than placebo for the management of recurrent aggression .
Conclusions : Currently available RCTs do not support the efficacy of anticonvulsants as mood stabilizers in children .
There is some preliminary evidence from small RCTs of the efficacy of some anticonvulsants in the control of aggression and behavioral dyscontrol in conduct disorder , autism , and intellectual disability
***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 aim of this study was to study valproate  efficacy and safety for aggression in children and adolescents with pervasive developmental disorders ( PDD ) . METHODS In this prospect i ve double-blind , placebo-controlled study , 30 subjects ( 20 boys , 10 girls ) 6 - 20 years of age with PDD and significant aggression were r and omized and received treatment with valproate ( VPA ) or placebo ( PBO ) for 8 weeks as out patients . Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8 . RESULTS No treatment difference was observed statistically between VPA and PBO groups . The Aberrant Behavior Checklist -- Community Scale ( ABC-C ) Irritability subscale was the primary outcome measure ( p = 0.65 ) , and CGI -- Improvement ( p = 0.16 ) and OAS ( p = 0.96 ) were secondary outcome measures . Increased appetite and skin rash were significant side effects . Only 1 subject was dropped from the study owing to side effects , notably a spreading skin rash , which then resolved spontaneously . Two subjects receiving VPA developed increased serum ammonia levels , one with an associated parent report of slurred speech and mild cognitive slowing . Post study , of 16 VPA and PBO subjects receiving VPA , 10 subjects demonstrated sustained response , 4 of whom later attempted taper , with significant relapse of aggression . CONCLUSION The present negative findings can not be viewed as conclusive , partly owing to the large placebo response , subject heterogeneity , and size of the groups . Larger studies are needed to exp and upon these findings OBJECTIVE To compare the efficacy and safety of divalproex extended-release ( ER ) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study . METHOD In the double-blind study , 150 patients ( manic or mixed episode , aged 10 - 17 years ) with baseline Young Mania Rating Scale ( YMRS ) score of 20 or higher were r and omized to once-daily placebo or divalproex ER , which was titrated to clinical response or serum valproate concentration of 80 to 125 microg/mL. Sixty-six patients enrolled in the extension study . RESULTS In the double-blind study , a treatment effect was not observed with divalproex ER based on change in mean YMRS score  ( divalproex ER -8.8 [ n = 74 ] ; placebo -7.9 [ n = 70 ] ) or secondary measures . Divalproex was similar to placebo based on incidence of adverse events . Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events . Mean ammonia levels increased in the divalproex ER group , but only one patient was symptomatic . In the long-term study , YMRS scores decreased modestly ( 2.2 points from baseline ) . The most common adverse events were headache and vomiting . CONCLUSIONS The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder , mixed or manic state . Further controlled trials are required to confirm or refute the findings from this study OBJECTIVE This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents . METHOD A total of 116 out patients 7 to 18 years of age with bipolar I disorder , manic or mixed , were recruited at 20 centers in the United States and r and omly assigned to receive 7 weeks of double-blinded , flexibly dosed treatment with oxcarbazepine ( maximum dose 900 - 2400 mg/day ) or placebo . The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale ( YMRS ) , using the last-observation-carried-forward method . RESULTS Oxcarbazepine ( mean dose=1515 mg/day ) did not significantly improve YMRS scores at endpoint compared with placebo [ adjusted mean change : oxcarbazepine , -10.90 ( N=55 ) ; placebo , -9.79 ( N=55 ) ] . Dizziness , nausea , somnolence , diplopia , fatigue , and rash were each reported in at least 5 % of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group . The majority of adverse events were mild to moderate and occurred during the titration period . Eleven patients ( 19 % ) in the oxcarbazepine group discontinued the study because of adverse events , compared with two ( 4 % ) in the placebo group . CONCLUSIONS Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths . While the overall adverse event profile was similar to that reported for patients with epilepsy , the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population OBJECTIVE The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children , 3 - 7 years of age , with bipolar I disorder ( BPD ) , during a mixed or manic episode . METHODS Forty-six children with Diagnostic and Statistical Manual of Mental Disorders . 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of bipolar disorder , manic , hypomanic , or mixed episode , were recruited over a 6 year period from two academic outpatient programs for a double-blinded , placebo-controlled trial in which subjects were r and omized in a 2:2:1 ratio to risperidone solution , valproic acid , or placebo . RESULTS After 6 weeks of treatment , the least-mean Young Mania Rating Scale ( YMRS ) total scores change , adjusted for baseline YMRS scores , from baseline by treatment group was : Valproic acid 10.0±2.46 ( p=0.50 ) ; risperidone 18.82±1.55 ( p=0.008 ) ; and placebo 4.29±3.56 ( F=3.93 , p=0.02 ) . The mixed models for repeated measure ( MMRM ) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects ( p=0.008 ) but not for valproic acid-treated subjects versus placebo-treated subjects ( p=0.50 ) . Treatment with risperidone over 6 weeks led to increased prolactin levels , liver functions , metabolic measures , and weight/body mass index ( BMI ) . Treatment with valproic acid led to increases in weight/ BMI and decreases in total red blood cells ( RBC ) , hemoglobin , and hematocrit . CONCLUSIONS In this small sample of preschool children with BPD  , risperidone demonstrated clear efficacy versus placebo , whereas valproic acid did not . The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics , and that , therefore , frequent laboratory and weight monitoring are warranted OBJECTIVE To determine whether divalproex sodium ( DVPX ) was superior to lithium carbonate ( Li+ ) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX ( Li+/DVPX ) pharmacotherapy . METHOD Youths ages 5 - 17 years with bipolar I or II disorder were initially treated with Li /DVPX . Patients meeting remission criteria for four consecutive weeks were then r and omized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks . Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures . RESULTS Patients were recruited between July 1998 and May 2002 . One hundred thirty-nine youths with a mean ( SD ) age of 10.8 ( 3.5 ) years were initially treated with Li+/DVPX for a mean ( SD ) duration of 10.7 ( 5.4 ) weeks . Sixty youths were then r and omized to receive monotherapy with Li+ ( n = 30 ) or DVPX ( n = 30 ) . The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse ( p = .55 ) or survival time until discontinuation for any reason ( p = .72 ) . CONCLUSIONS DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy OBJECTIVE There is evidence for the efficacy and safety of clonazepam ( CZP ) in adult anxiety disorders , but no formal studies to substantiate clinical reports of similar benefit in children with anxiety disorders . METHOD In this double-blind pilot study , 15 children , aged 7 to 13 years , entered a r and omly assigned , double-blind crossover trial of 4 weeks of CZP ( up to 2 mg/day ) and 4 weeks of placebo . RESULTS Twelve children completed the trial . All but 1 had a diagnosis of separation anxiety disorder , and all but 2 had comorbid diagnoses . Nine children appeared to have moderate to significant clinical improvement , but statistical comparisons on several ratings failed to confirm a trend in favor of CZP . Side effects of drowsiness , irritability , and /or oppositional behavior were notable in 10 children in the CZP phase compared with 5 in the placebo phase . CONCLUSIONS Clonazepam was believed to have clinical benefit for some children , but this was not confirmed statistically in this small sample . Problematic side effects of drowsiness and disinhibition were common and possibly were due to rapid titration The objective of this study was to investigate the effectiveness of levetiracetam for the treatment of  tics in children with Tourette syndrome ( TS ) .  Levetiracetam , an atypical anticonvulsant , has been suggested in open-label protocol s to be an effective tic-suppressing agent in individuals with TS . A double blind , r and omized , placebo-controlled , cross-over trial was performed to investigate this medication in children with moderate to moderately-severe tics . Subjects received , in a r and omized sequence , 4-weeks of levetiracetam ( maximum dose 30 mg/kg/day ) or placebo , with a 2-week intervening washout period between cycles . Primary outcome measures included two separate scales from the Yale Global Tic Severity Scale ; the Total Tic score and the Total overall score . Measures were assessed at baseline , prior to r and omization , on Day 28 ( end of Phase 1 ) , on Day 42 ( baseline for second phase ) and on Day 70 ( end of Phase 2 ) . Twenty-two subjects ( 21 boys and 1 girl ) with TS , mean age 12.2 + /- 2.3 years , range 8 to 16 years , participated . A mild reduction in tics occurred during both the levetiracetam and placebo treatment phases . There was no significant difference between treatments and no evidence of sequence or cross-over effects . In conclusion , Levetiracetam is not more beneficial than placebo in suppressing tics in children with TS OBJECTIVE The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium . METHOD Twenty outpatient children and adolescents ( ages 10 - 18 ) with a disruptive behavior disorder ( oppositional defiant disorder or conduct disorder ) met the specific criteria for explosive temper and mood lability . They received 6 weeks of divalproex treatment and 6 weeks of placebo by r and om assignment . Independent evaluators blind to group assignment assessed response at the end of each phase . RESULTS At the end of phase 1 , eight of 10 subjects had responded to divalproex ; zero of 10 had responded to placebo . Of the 15 subjects who completed both phases , 12 has superior response taking divalproex . CONCLUSIONS This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents BACKGROUND New treatments for conduct disorder are sorely needed . We aim ed to test the efficacy of divalproex sodium for the treatment of conduct disorder . METHOD Seventy-one youths with conduct disorder according to DSM-IV criteria were enrolled in a r and omized , controlled , 7-week clinical trial . Subjects were all adolescent males with at least 1 crime conviction . Subjects were r and omized into high- and low-dose conditions and were openly managed by a clinical team . Subjects and independent outcome raters were blinded to condition . Clinical Global Impressions-Severity of Illness ( CGI-S ) and CGI-Improvement ( CGI-I ) ratings , Weinberger Adjustment Inventory ratings , and staff ratings of behavioral privilege were used to assess outcome . RESULTS Intent-to-treat analyses showed significant associations between assignment to the high-dose condition and ratings on the CGI-S ( p = .02 ) and CGI-I ( p = .0008 ) . Self-reported weekly impulse control was significantly better in the high-dose condition ( p < .05 ) , and association between improvement in self-restraint and treatment condition was of borderline statistical significance ( p < .06 ) . Parallel analyses comparing outcome by blood drug level achieved strengthened the results , as expected . 
    Output:
    