***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Lithium is a well-established treatment for bipolar I disorder in adults . However , there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents . We aim ed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients . Methods Lithium concentrations , Young Mania Rating Scale ( YMRS ) and Clinical Global Impressions-Improvement ( CGI-I ) scores over 24 weeks were available from 61 paediatric patients with bipolar I disorder . The population pharmacokinetics/pharmacodynamics were co-modelled . Concentrations and clinical effects following several dosage regimens were predicted by Monte Carlo simulations . Results The pharmacokinetics were well characterised by a two compartment model with linear elimination . Including the effect of total body weight ( TBW ) or lean body weight ( LBW ) on clearance and volume of distribution decreased the unexplained inter-individual variability by up to 12 % . The population mean ( inter-individual variability ) clearance was 1.64 L/h/53 kg LBW0.75 ( 19 % ) and central volume of distribution 23.6 L/53 kg LBW ( 6.8 % ) . The average lithium concentration over a dosing interval required for a 50 % reduction in YMRS was 0.711 mEq/L ( 59 % ) . A maintenance dose of 25 mg/kg TBW/day lithium carbonate in two daily doses was predicted to achieve a ≥50 % reduction in YMRS in 74 % of patients , while ~8 % of patients would be expected to have trough concentrations above the nominal safety threshold of 1.4 mEq/L. Therefore , therapeutic drug monitoring will still be required even with these dosing strategies . Conclusions When accounting for body size , the pharmacokinetic parameters in paediatric patients were within the range of estimates from adults . Pharmacokinetic/pharmacodynamic modelling supported development of practical scientifically-based dosage regimens for paediatric patients Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Adolescents with acute psychotic mania were treated with lithium and adjunctive haloperidol as part of a lithium efficacy study . If the psychosis completely resolved , haloperidol was discontinued after 1 week of therapeutic lithium levels . Our first five subjects experienced a rapid exacerbation of symptoms , which responded to restarting haloperidol . A longer duration of adjunctive antipsychotic treatment is necessary in adolescents with bipolar psychosis Background The purpose of the study was to determine the effectiveness and tolerability of quetiapine as a maintenance treatment preventing against relapse or recurrence of acute mood episodes in adolescent patients diagnosed with bipolar disorder . Methods Consenting patients meeting DSM-IV lifetime criteria for a bipolar disorder and clinical ly appropriate for maintenance treatment were enrolled in a 48-week open prospect i ve study . After being acutely stabilized ( CGI-S ≤ 3 for 4 consecutive weeks ) , patients were started or continued on quetiapine and other medications were weaned off over an 8-week period . Quetiapine monotherapy was continued for 40-weeks and other mood stabilizers or antidepressants were added if clinical ly indicated . A neurocognitive test battery assessing the most reliable findings in adult patients was administered at fixed time points throughout the study to patients and matched controls . Results Of the 21 enrolled patients , 18 completed the 48-week study . Thirteen patients were able to be maintained without relapse or recurrence in good quality remission  on quetiapine monotherapy , while 5 patients required additional medication to treat impairing residual depressive and /or anxiety symptoms . According to symptom ratings and global functioning scores , the quality of remission for all patients was very good . Neurocognitive test performance over treatment was equivalent to that of a matched control group of never ill adolescents . Quetiapine was generally well tolerated with no serious adverse effects . Conclusion This study suggests that a proportion of adolescent patients diagnosed with bipolar disorder can be successfully maintained on quetiapine monotherapy . The good quality of clinical remission and preserved neurocognitive functioning underscores the importance of early diagnosis and effective stabilization . Clinical Trials OBJECTIVE Both the diagnosis and treatment of bipolar disorder in youth remain the subject of debate . In the Treatment of Early Age Mania ( TEAM ) study , risperidone was more effective than lithium or divalproex in children diagnosed with bipolar mania and highly comorbid with attention-deficit/hyperactivity disorder ( ADHD ) . We search ed for treatment moderators and predictors of outcome . METHOD TEAM was a multi-site , 8-week , r and omized clinical trial of risperidone , lithium , or divalproex in 279 medication-naïve patients , aged 6 through 15 years , with a DSM-IV diagnosis of bipolar disorder currently in manic or mixed phase . Outcome measures included binary end-of-treatment responder status and change in the Kiddie Schedule for Affective Disorders and Schizophrenia ( K-SADS ) Mania Rating Scale ( KMRS ) . Baseline demographics and clinical characteristics were tested as modifiers of treatment effect and as overall predictors of outcome . RESULTS Moderator effects were detected for site , ADHD , and obesity . Across sites , the response ratio ( RR ) for risperidone versus lithium ranged from 1.2 ( 95 % confidence interval [ CI ] = 0.8 - 1.7 ) to 8.3 ( 95 % CI = 1.1 - 60.8 ) , and for risperidone versus divalproex from 1.3 ( 95 % CI = 0.8 - 2.2 ) to 10.5 ( 95 % CI = 1.4 - 77.7 ) . The RR for risperidone versus lithium was 2.1 for patients with ADHD , but 1.0 for those without ADHD , and 2.3 ( 95 % CI = 1.6 - 3.3 ) for nonobese patients , but 1.1 ( 95 % CI = 0.6 - 2.0 ) for obese ones . Older age and less severe ADHD symptoms were associated with greater improvement on the KMRS . CONCLUSIONS Risperidone was more effective than lithium or divalproex across the demographics and clinical characteristics of the sample , but the magnitude of its effect was influenced by site-related characteristics and presence of ADHD . Clinical trial registration information -- Treatment of Early Age Mania ; http:// clinical trials.gov/ ; NCT00057681 Objective : In adults with established bipolar disorder ( BD ) , differential response to  mood stabilizers  has been associated with the clinical profile . Long-term treatment studies of youth with BD are lacking . This paper provides longitudinal observations of response to  mood stabilizers  early in the course of illness in youth with BD . Method : We report on 15 research patients who , as adolescents , met DSM-IV lifetime criteria for a bipolar spectrum disorder and required long-term treatment . These youths derived from families with one parent having BD whose course and long-term treatment response were determined in accordance with research criteria . The patients were offered lithium , and if they failed to respond or refused it , they were treated with either an anticonvulsant or an atypical antipsychotic . Using a vali date d scale , an independent rater retrospectively blindly scored the response to long-term treatment . Results : Those patients who stabilized on  lithium  derived from lithium-responsive families , whereas those who stabilized on an  antipsychotic  derived from lithium-nonresponsive families . The clinical course in the youths stabilized by lithium differed from that in the youths stabilized by an atypical antipsychotic . Conclusions : Our findings suggest that the clinical profile may help in selecting effective stabilizing treatment and that a proportion of youth can be stabilized on monotherapy . This is a small case series with nonr and om treatment assignment , and the findings should be considered tentative BACKGROUND : Lithium is a benchmark treatment for bipolar disorder in adults . Definitive studies of lithium in pediatric bipolar I disorder ( BP-I ) are lacking . METHODS : This multicenter , r and omized , double-blind , placebo-controlled study of pediatric participants ( ages 7–17 years ) with BP-I/manic or mixed episodes compared  lithium ( n = 53 )  versus placebo ( n = 28 ) for up to 8 weeks . The a priori primary efficacy measure was change from baseline to the end of study ( week 8/ET ) in the Young Mania Rating Scale ( YMRS ) score , based on last-observation-carried-forward analysis . RESULTS : The change in YMRS score was significantly larger in lithium-treated participants ( 5.51 [ 95 % confidence interval : 0.51 to 10.50 ] ) after adjustment for baseline YMRS score , age group , weight group , gender , and study site ( P = .03 ) . Overall Clinical Global Impression – Improvement scores  favored lithium ( n = 25 ; 47 % very much/much improved ) compared with placebo ( n = 6 ; 21 % very much/much improved ) at week 8/ET ( P = .03 ) . A statistically significant increase in thyrotropin concentration was seen with lithium ( 3.0 ± 3.1 mIU/L ) compared with placebo ( –0.1 ± 0.9 mIU/L ; P < .001 ) . There was no statistically significant between-group difference with respect to weight gain . CONCLUSIONS : Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial . Lithium was generally well tolerated in this patient population and was not associated with weight gain , distinguishing it from other agents commonly used to treat youth with bipolar disorder OBJECTIVE This prospect i ve 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder : ( 1 ) divalproex sodium plus risperidone ( DVPX+Risp ) , or ( 2 ) lithium plus risperidone ( Li+Risp ) . METHODS Thirty-seven ( 37 ) subjects aged 5 and 18 ( age=12.1+/-3.5 years ) with DSM IV current mixed or manic episode and Young Mania Rating Scale ( YMRS ) score > 20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month , prospect i ve open-label trial . Outcome measures included the YMRS , Clinical Global Impression Scale for Bipolar Disorder ( CGI-BP ) , Child Depression Rating Scale-Revised ( CDRS-R ) as well as measures of safety and tolerability . RESULTS Effect sizes ( Cohen 's d ) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp .  Response rates ( > or=50 % change from baseline YMRS score at the end of study ) were 80 % for DVPX+Risp and 82.4 % for Li+Risp . Both combination treatments were well tolerated . Significant improvements ( p<0.001 ) from baseline were seen for mean scores on all efficacy measures , i.e. , YMRS , CGI-BP , and CDRS-R. There were no significant group differences in safety or tolerability , and no serious adverse events during the 6-month trial . CONCLUSION Both DVPX+Risp and Li+Risp show strong effects coupled with safety and tolerability in treating children and adolescents with manic or mixed episodes associated with type I bipolar disorder OBJECTIVES This r and omized , double-blind , placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex ( DVP ) for acute mania in adolescents with bipolar disorder . It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder . Furthermore , it was hypothesized that quetiapine would be well tolerated . METHOD Thirty manic or mixed bipolar I adolescents ( 12 - 18 years ) received an initial DVP dose of 20 mg/kg and were r and omly assigned to 6 weeks of combination therapy with quetiapine , which was titrated to 450 mg/day ( n = 15 ) or placebo ( n = 15 ) . Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale ( YMRS ) score and YMRS response rate . Safety and tolerability were assessed weekly . RESULTS The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group ( F(1,27 ) = 5.04 , p = .03 ) . Moreover , YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group ( 87 % versus 53 % ; Fisher exact test , p = .05 ) . No significant group differences from baseline to endpoint in safety measures were noted . Sedation , rated as mild or moderate , was significantly more common in the DVP + quetiapine group than in the DVP + place 
    Output:
    
Lithium was not associated with serious adverse events , and was generally well tolerated with common side effects similar to those reported in adults .
Limited data suggests that lithium may be an effective and tolerable treatment for some forms of paediatric mania .
However , lithium is clearly inferior in efficacy to risperidone in prepubertal patients diagnosed with protracted manic/mixed episodes and comorbid ADHD .