title: A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. A double-blind, randomized, placebo-controlled trial of divalproex extended-release in the treatment of bipolar disorder in children and adolescents. A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. Placebo-controlled trial of valproic Acid versus risperidone in children 3-7 years of age with bipolar I disorder. Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder. Clonazepam in childhood anxiety disorders. A double blind randomized placebo control trial of levetiracetam in Tourette syndrome. Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. Divalproex sodium for the treatment of conduct disorder: a randomized controlled clinical trial. Divalproex Sodium vs Placebo for the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorders A double-blind randomized pilot study comparing quetiapine and divalproex for adolescent mania. Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. Adjunctive Maintenance Lamotrigine for Pediatric Bipolar I Disorder: A Placebo-Controlled, Randomized Withdrawal Study. Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment. Carbamazepine in aggressive children with conduct disorder: a double-blind and placebo-controlled study. The effect of sulthiame on disturbed behaviour in mentally subnormal patients. The use of sulthiame with disturbed mentally subnormal patients. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder. Double-blind, placebo-controlled trial of divalproex monotherapy in the treatment of symptomatic youth at high risk for developing bipolar disorder. Randomised controlled study-efficacy of clonidine versus carbamazepine in children with ADHD. An open-label trial of divalproex in children and adolescents with bipolar disorder.
abstract: 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 . CONCLUSION This preliminary study in a most difficult population suggests a role for divalproex sodium in the treatment of conduct disorder . Divalproex sodium improved self-reported impulse control and self-restraint , variables shown to be predictive of criminal recidivism . Studies are needed of longer-term impact and side-effect profiles . This is one of few controlled psychopharmacologic studies of conduct disorder Autism spectrum disorders ( ASDs ) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests . Irritability/aggression is a significant comorbid symptom in this population , which greatly impacts burden of care . This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD . This was a 12-week r and omized , double-blind , placebo-controlled trial . All efficacy measures were obtained by an independent evaluator blinded to r and omization condition and side effects . A total of 55 subjects gavetheir consent and 27 were r and omized in a 1 : 1 manner ( mean age 9.46±2.46 , mean nonverbal IQ 63.3±23.9 ) . Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects ( increased irritability ) . Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement , which focused on irritability . Overall , 62.5 % of divalproex subjects vs 9 % of placebo subjects were responders ( CGI-irritability OR : 16.7 , Fisher 's exact p=0.008 ) . A statistically significant improvement was also noted on the ABC-Irritability subscale ( p=0.048 ) . There was a trend for responders to have higher valproate blood levels compared with nonresponders . This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD . Larger sample follow-up studies are warranted OBJECTIVE To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania . METHOD Fifty adolescents ( ages 12 - 18 years ) with bipolar I disorder , manic or mixed episode , were r and omized to quetiapine ( 400 - 600 mg/day ) or divalproex ( serum level 80 - 120 microg/mL ) for 28 days for this double-blind study , which was conducted from July 2002 through January 2004 . The primary efficacy measure was change in Young Mania Rating Scale ( YMRS ) score across the study period . RESULTS Repeated measures analysis of variance using the last-observation carried forward data indicated no statistically significant group difference in YMRS scores across the 28 days of the study ( p = 0.3 ) . Mixed regression analyses ( comparison of slopes ) revealed that improvement in YMRS scores occurred more rapidly in the quetiapine than in the divalproex group for both the last-observation carried forward ( p = 0.01 ) and observed data ( p = 0.03 ) . Response and remission rates were significantly greater in the quetiapine than in the divalproex group ( p < .03 ) . Rates of adverse events did not differ significantly between groups . CONCLUSIONS The results suggest that quetiapine is at least as effective as divalproex in the treatment of acute manic symptoms associated with adolescent bipolar disorder ; however , a quicker reduction of manic symptoms may occur with quetiapine as compared with divalproex . Quetiapine may be useful as monotherapy for the treatment of adolescents with manic or mixed episodes , although placebo-controlled studies are necessary OBJECTIVE To develop effect sizes for 3 mood stabilizers -- lithium , divalproex sodium , and carbamazepine -- for the acute-phase treatment of bipolar I or II disorder , mixed or manic episode , in children and adolescents aged 8 to 18 years . METHOD Forty-two out patients with a mean age of 11.4 years ( 20 with bipolar I disorder and 22 with bipolar II disorder ) were r and omly assigned to 6 weeks of open treatment with either lithium , divalproex sodium , or carbamazepine . The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale ( Y-MRS ) . RESULTS Using a > or = 50 % change from baseline to exit in the Y-MRS scores to define response , the effect size was 1.63 for divalproex sodium , 1.06 for lithium , and 1.00 for carbamazepine . Using this same response measure with the intent-to-treat sample , the response rates were as follows : sodium divalproex , 53 % ; lithium , 38 % ; and carbamazepine , 38 % ( chi 2(2 ) = 0.85 , p = .60 ) . All 3 mood stabilizers were well tolerated , and no serious adverse effects were seen . CONCLUSIONS Divalproex sodium , lithium , and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode OBJECTIVE This study aim ed to compare the efficacy of lamotrigine versus placebo in 10- to 17-year-olds with bipolar I disorder ( BP-I ) who were receiving conventional bipolar disorder treatment . METHOD In this r and omized withdrawal trial , patients with BP-I of at least moderate severity  received lamotrigine during an ≤18-week open-label phase . Patients who maintained a stable lamotrigine dose for ≥2 weeks and Clinical Global Impression-Bipolar Severity of Illness ( CGI-BP[S ] ) score of ≤3 for ≥6 consecutive weeks were r and omized to double-blind lamotrigine or placebo for ≤36 weeks . RESULTS Of 301 patients enrolled , 298 comprised the open-label intention-to-treat population , with 173 ( 58 % ) r and omized . Of these patients , 41 ( 24 % ) completed the study . In the open-label phase , the mean ( SD ) baseline CGI-BP(S ) rating was 4.4 ( 0.57 ) , and the mean ( st and ard error [ SE ] ) time to stabilization was 101 ( 1.6 ) days . During the r and omized phase , mean ( SE ) time to occurrence of a bipolar event ( TOBE )  for lamotrigine versus placebo ( primary endpoint ) was 155 ( 14.7 ) versus 50 ( 3.8 ) , 163 ( 12.2 ) versus 120 ( 12.2 ) , and 136 ( 15.4 ) versus 107 ( 13.8 ) days for the 3 index mood states ( depressed , manic/hypomanic , mixed ) . The primary stratified log-rank analysis of TOBE was not statistically significant ( hazard ratio [ HR ] = 0.63 ; p = .072 ) ; however , the prespecified Cox regression analysis favored lamotrigine ( p = .047 ) . In 13- to 17-year-olds , log-rank analysis of TOBE significantly favored lamotrigine ( HR = 0.46 ; p = .015 ) , but not in 10- to 12-year-olds ( HR = 0.93 ; p = .877 ) . Dermatologic events were reported in 4 % ( open-label phase ) and 2 % ( r and omized phase ) of patients receiving  lamotrigine . Suicidality-related adverse events were reported in 7 % ( open-label phase ) and 7 % ( r and omized phase ) of patients receiving lamotrigine . CONCLUSION Although the primary analysis failed to detect a benefit of add-on lamotrigine for BP-I in 10- to 17-year-olds , lamotrigine may be effective in a subset of older adolescents . Clinical trial registration information-Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients ; http:// clinical trials.gov/ ; NCT00723450 OBJECTIVE The purpose of the present study was to evaluate the efficacy of divalproex for reducing aggressive behavior among children 6 to 13 years old with attention deficit hyperactivity disorder ( ADHD ) and a disruptive disorder whose chronic aggression was underresponsive to a prospect i ve psychostimulant trial . METHOD Children received open stimulant treatment during a lead-in phase that averaged 5 weeks . Agent and dose were assessed weekly and modified to optimize response . Children whose aggressive behavior persisted at the conclusion of the lead-in phase were r and omly assigned to receive double-blind , flexibly dosed divalproex or a placebo adjunctive to stimulant for 8 weeks . Families received weekly behavioral therapy throughout the trial . The primary outcome measure was the proportion of children whose aggressive behavior remitted , defined by post-trial ratings of negligible or absent aggression . RESULT A significantly higher proportion of children r and omly assigned to divalproex  met remission criteria ( eight out of 14 [ 57 % ] ) than those r and omly assigned to placebo ( two out of 13 [ 15 % ] ) . Divalproex was generally well tolerated . CONCLUSIONS Among children with ADHD whose chronic aggressive behavior is refractory to optimized stimulant treatment , the addition of divalproex increases the likelihood that aggression will remit . A larger trial is necessary to specify with greater precision the magnitude of benefit for adjuvant divalproex OBJECTIVE The Treatment of Early Age Mania ( TEAM ) study evaluated lithium , risperidone , and divalproex sodium ( divalproex ) in children with bipolar I disorder who were naive to antimanic medication , or were partial or nonresponders to 1 of 3 study medications . This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders , respectively . METHOD TEAM is a r and omized , controlled trial of individuals ( N = 379 ) aged 6 to 15 years ( mean ± SD = 10.2 ± 2.7 years ) with DSM-IV bipolar I disorder ( mixed or manic phase ) . Participants ( n = 154 ) in this report were either nonresponders or partial responders to 1 of the 3 study medications . Nonresponders ( n = 89 ) were r and omly assigned to 1 of the other 2 antimanic medications and cross-tapered . Partial responders ( n = 65 ) were r and omly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication . Adverse event ( AE ) rates are reported only for the add-on group . RESULTS Response rate for children switched to risperidone ( 47.6 % ) was higher than for those switched to either lithium ( 12.8 % ; p = .005 ; number needed to treat [ NNT ] = 3 ; 95 % CI = 1.71 - 9.09 ) or divalproex ( 17.2 % ; p = .03 ; NNT = 3 ; 95 % CI = 1.79 - 20.10 ) ; response rate for partial responders who added risperidone ( 53.3 % ) was higher than for those who added divalproex ( 0 % ; p = .0002 ; NNT = 2 ; 95 % CI = 1.27 - 3.56 ) and trended higher for lithium ( 26.7 % ; p = .07 ; NNT = 4 ) . Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication . Weight gain ( kg ) was observed for all add-on medications : lithium add-on ( n = 29 of 30 ) = 1.66 ± 1.97 ; risperidone add-on ( n = 15 of 15 ) = 2.8 ± 1.34 ; divalproex add-on ( n = 19 of 20 ) = 1.42 ± 1.96 . There was no evidence at the 5 % significance level that the average weight gain was different by study medication for partial responders ( p = .07 , 1-way analysis of variance ) . CONCLUSION Risperidone appears to be more useful than lithium or divalproex for children with bipolar I disorder and other comorbid conditions who are nonresponders or partial responders to an initial antimanic medication trial . Clinical trial registration information- Study of Outcome and Safety of Lithium , Divalproex and Risperidone for Mania in Children and Adolescents ( TEAM ) ; http:// clinical trials.gov/ ; NCT00057681 OBJECTIVE To assess critically the short-term efficacy and safety of carbamazepine in the reduction of aggressiveness in children with diagnosed conduct disorder . METHOD Subjects were children aged 5 to 12 years who were hospitalized for treatment-resistant aggressiveness and explosiveness and who had diagnosed conduct disorder . The study was double-blind and placebo-controlled , using a parallel-groups design . Following a 2-week placebo baseline period , children who met the aggression criteria were r and omly assigned to treatments for 6 weeks ; the study ended with a 1-week posttreatment placebo period . Multiple raters rated the children independently , using multiple rating scales under four conditions . The main outcome measures included the Overt Aggression Scale , the Global Clinical Judgments ( Consensus ) Scale , and the Children 's Psychiatric Rating Scale . RESULTS Twenty-two children , aged 5.33 to 11.7 years , completed the study .  Carbamazepine was not superior to placebo at optimal daily doses ranging from 400 to 800 mg , mean 683 mg , at serum levels of 4.98 to 9.1 micrograms/mL. Untoward effects associated with administration of carbamazepine were common . CONCLUSIONS In this modest sample of children , the superiority of carbamazepine over placebo in reducing aggressive behavior was not demonstrated Sulthiame was investigated as a tranquillizer in a double-blind trial on 34 severely subnormal patients with disturbed behaviour . A special rating scale was used by nurses for the assessment of behavioural changes in hyperactivity , aggressiveness , destructiveness and anti-sociability . The results showed that sulthiame was significantly effective in reducing disturbed behaviour in general , and aggressiveness and hyperactivity in particular . Only one case of hyperpnoea was observed , in an epileptic patient Forty-two severely subnormal , hospitalized patients with marked and apparently intractable behaviour abnormalities took part in a doubleblind , cross-over trial of sulthiame , which was investigated as a tranquillizer rather than as an anticonvulsant . Detailed assessment s of behavioural changes were made , with the use of rating scales , by nursing observers . The findings were as follows : 1 . Sulthiame was significantly effective in reducing the incidence of disturbed behaviour . 2 . There was insufficient evidence to suggest that it affected the variety of disturbed behaviour . 3 . Most of the patients had taken part in an earlier trial with pericyazine and chlorpromazine and had shown no improvement ; this suggests that sulthiame may well be effective in cases where other tranquillizers have failed . 4 . The so-called ` placebo effect ' did not material ize . 5 . There were no observable side effects during the trial . 6 . The addition of sulthiame to st and ard anticonvulsant therapy brought about a decrease in seizure frequency in only one of 25 epileptic patients OBJECTIVE To determine the relative effects of risperidone and divalproex in pediatric mania . METHODS This is a double-blind , r and omized , outpatient clinical trial with 66 children and adolescents ( mean age= 10.9 ± 3.3 years ; age range= 8 - 18 years ) with mania who were r and omly assigned to either risperidone ( 0.5 - 2 mg/day , n= 33 ) or divalproex ( 60 - 120 μg/mL , n= 33 ) for a six-week period . Measures included the Young Mania Rating Scale ( YMRS ) and Child Depression Rating Scale-Revised ( CDRS-R ) . RESULTS Mixed-effects regression models , with interaction between time and the active drug as predictors , found that the risperidone group had more rapid improvement than the divalproex group ( p < 0.05 ) , although final scores did not differ significantly between groups . Mixed models using only those subjects who completed the six-week study found similar results . The response rate on YMRS was 78.1 % for risperidone and 45.5 % for divalproex ( p < 0.01 ) . The remission rate for risperidone was 62.5 % , compared with 33.3 % for divalproex ( p < 0.05 ) . Improvement on the CDRS-R was significantly higher for the risperidone group relative to the divalproex group ( p < 0.05 ) . There were no significant differences between groups in safety , but subject retention was significantly higher at study endpoint in the risperidone group ( p < 0.01 ) . Dropout rate was 24 % in the risperidone group and 48 % in the divalproex group , with increased irritability being the most common reason for dropout in the latter . There was no significant weight gain in either group . CONCLUSION Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex . Although the results suggest that both drugs are safe , risperidone 's lower attrition rate and lower rate of adverse events may suggest better toleration . Clinical trials with larger sample s are required to confirm these preliminary findings OBJECTIVE To determine if divalproex sodium was superior to placebo in the treatment of symptomatic youths who suffer from a bipolar spectrum disorder and who also have a parent with a diagnosis of a bipolar illness . METHOD Youths , ages 5 to 17 years , meeting DSM-IV criteria for bipolar disorder not otherwise specified ( NOS ) or cyclothymia who also had at least 1 biological parent with bipolar illness were r and omly assigned in a double-blind fashion to receive treatment with either dival-proex sodium or placebo for up to 5 years . Study participation ended if the subject required additional clinical intervention , if the patient developed treatment-related adverse events , or if the participant was not adherent with study procedures . The primary outcome measure was time to study discontinuation for any reason . The study was conducted from August 1997 to April 2003 . RESULTS Fifty-six youths with a mean ( SD ) age of 10.7 ( 3.1 ) years were r and omly assigned and received either divalproex sodium ( N = 29 ) or placebo ( N = 27 ) . In spite of statistical power of 80 % to detect hazard ratios of 2.2 or larger , the treatment groups did not significantly differ in survival time for discontinuation for any reason ( p = .93 ) or discontinuation due to a mood event ( p = .55 ) . Changes in mood symptom ratings and psychosocial functioning from baseline to study discontinuation did not differ between groups ( most significant p > .14 ) . However , both groups did show improvements in mood symptoms and psychosocial functioning over time ( all p values < .002 ) . One patient , from the placebo group , ended study participation due to an adverse event . CONCLUSION These results suggest that , although well tolerated , divalproex sodium does not produce clinical ly meaningful improvements in the treatment of symptomatic youths suffering from either bipolar NOS or cyclothymia who are at genetic risk for developing bipolar disorder BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) is one of the most common childhood psychiatric disorder with a prevalence of 8 - 12 % . Even though psychostimulants remain the treatment of choice , its cost and availability in developing countries limits the usage of the drug . In view of free availability and low cost , a R and omized controlled study was carried out using two second line drugs ( clonidine and carbamazepine ) in a tertiary care hospital , Pondicherry , South India . OBJECTIVE To compare the efficacy of clonidine and carbamazepine in children with ADHD . METHOD With approval of ethics committee , a prospect i ve , Double-blind , R and omized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD ( age group 4 - 12 years ) , over a period of 2 years ( 2005 - 07 ) in a tertiary care hospital , Pondicherry , South India . RESULTS Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine . Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions . CONCLUSION Clonidine can be a safer and cheaper alternative in treatment of children with ADHD , with a predominant effect on their hyperactivity and impulsivity symptoms OBJECTIVE This study evaluated the safety and effectiveness of divalproex sodium ( Depakote ) in the treatment of youths with bipolar disorder . METHOD Forty bipolar disorder patients aged 7 to 19 years , with a manic , hypomanic , or mixed episode , enrolled in an open-label study of  divalproex ( 2 - 8 weeks ) , followed by a double-blind , placebo-controlled period ( 8 weeks ) . RESULTS Twenty-two subjects ( 61 % ) showed > or = 50 % improvement in Mania Rating Scale ( MRS ) scores during the open-label period . Significant ( < .001 ) improvements from baseline were seen for mean scores of all efficacy measures , including the MRS , Manic Syndrome Scale , Behavior and Ideation Scale , Brief Psychiatric Rating Scale , Clinical Global Impressions Severity scale , and Hamilton Rating Scale for Depression . Of the 23 subjects who discontinued the study during the open-label period , 6 ( 15 % ) discontinued for ineffectiveness , 6 ( 15 % ) for intolerance , 6 ( 15 % ) for noncompliance , and 6 ( 15 % ) for other reasons . Adverse events were generally mild or moderate in severity , with the most common being headache , nausea , vomiting , diarrhea , and somnolence . Laboratory data results were unremarkable . Too few subjects participated in the double-blind period for statistical analysis . CONCLUSION This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths
target: 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
background: Aim : Anticonvulsant medications are frequently used in clinical practice to treat psychiatric disorders in children and adolescents , but the evidence for their efficacy is uncertain .
  We conducted a systematic review of published r and omized controlled trials ( RCT ) that assessed the psychiatric benefit of anticonvulsants  in patients under 18 years of age .