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 treatment of pediatric bipolar depression has not been well studied . The authors wished to prospect ively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode . METHOD This was an 8-week open-label trial of lamotrigine with 20 adolescents ages 12 - 17 years ( mean age 15.8 ; 7 boys , 13 girls ) with diagnoses of bipolar disorder I , II , or not otherwise specified , who were experiencing a depressive episode .  Lamotrigine was begun at 12.5 to 25 mg/day . Primary response criteria was a 1 or a 2 on the Clinical Global Impression-Improvement at week 8 . A secondary criterion was at least a 50 % decrease in Children 's Depression Rating Scale-Revised scores . RESULTS Nineteen subjects completed the trial . The mean final dose was 131.6 mg/day . Seven subjects were taking other psychotropic medications . Sixteen subjects ( 84 % ) responded by primary criteria , and 12 ( 63 % ) responded to our secondary criteria . Eleven subjects ( 58 % ) were considered in remission at week 8 . Young Mania Rating Scale and Overt Aggression Scale-Modified scores also decreased significantly during the trial . There was no significant weight change , rash , or other adverse effects during the trial . CONCLUSIONS Adolescents with bipolar depression appeared to respond to lamotrigine treatment , whether as adjunctive therapy or monotherapy , with decreases in depression , mania , and aggression . Larger , placebo-controlled studies of lamotrigine are needed in this population BACKGROUND Antidepressant-induced mania ( AIM ) has been described in bipolar disorder ( BD ) and has been associated with the short-allele of the serotonin transporter gene ( 5-HTT ) . We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD . METHODS Fifty-two children and adolescents ( 30 with BD and 22 with subthreshold manic symptoms , 15.1 + /- 3.4 years old ) , all with a parent with BD , were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment .  The 47 subjects with serotonin reuptake inhibitor ( SSRI ) exposure  were genotyped for the 5-HTT polymorphism . RESULTS Fifty percent of subjects were AIM + and 25.5 % had new onset of suicidal ideation . The AIM + and AIM - groups did not differ significantly in relation to allele ( p = .36 ) or genotype ( p = .53 ) frequencies of the 5-HTT polymorphism . The AIM + subjects were more likely to have more comorbidities ( 3.2 vs. 2.4 ; p = .02 ) and be BD type I ( p = .04 ) than AIM - subjects . CONCLUSIONS Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs . In this preliminary study , we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM OBJECTIVE To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania . METHODS This was an eight-week , open-label , prospect i ve study of ziprasidone monotherapy ( 57.3 + /- 33.9 mg/day ) in 21 bipolar youth [ manic , mixed , or bipolar not otherwise specified ( NOS ) ; 6 - 17 years old ] . Assessment s included the Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions-Improvement scale ( CGI-I ) , and Brief Psychiatric Rating Scale ( BPRS ) . Adverse events were assessed through spontaneous self-reports , vital signs , weight monitoring , and laboratory analysis . RESULTS Fourteen of the 21 youth ( 67 % ) completed the study .  Ziprasidone treatment was associated with clinical ly and statistically significant improvement in mean YMRS scores ( -10.8 + /- 8.4 , p < 0.0001 ) and 57 % had a CGI-I < or=2 at endpoint . Ziprasidone was well tolerated with no statistically significant increase in body weight ( 0.6 + /- 0.4 kg , p = 0.2 ) or QTc interval ( -3.7 + /- 4.7 , p = 0.5 ) . CONCLUSIONS Open-label ziprasidone treatment was associated with a significant short-term improvement of symptoms of pediatric bipolar disorder . Future placebo-controlled , double-blind studies are warranted The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder . The third version is based explicitly on the available evidence and presented , like previous Clinical Practice Guidelines , as recommendations to aid clinical decision making for practitioners : it may also serve as a source of information for patients and carers , and assist audit . The recommendations are presented together with a more detailed review of the corresponding evidence . A consensus meeting , involving experts in bipolar disorder and its treatment , review ed key areas and considered the strength of evidence and clinical implication s. The guidelines were drawn up after extensive feedback from these participants . The best evidence from r and omized controlled trials and , where available , observational studies employing quasi-experimental design s was used to evaluate treatment options . The strength of recommendations has been described using the GRADE approach . The guidelines cover the diagnosis of bipolar disorder , clinical management , and strategies for the use of medicines in short-term treatment of episodes , relapse prevention and stopping treatment . The use of medication is integrated with a coherent approach to psychoeducation and behaviour change BACKGROUND This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders . METHOD Out patients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder ( I , II , not otherwise specified , cyclothymia ) were eligible to receive up to 16 weeks of open-label treatment with  aripiprazole ( phase 1 ) . Patients were r and omized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization ( phase 2 ) . During phase 2 , patients either remained on their current aripiprazole regimen or began a double-blind taper with aripiprazole discontinued and switched to placebo . The primary outcome measure for phase 2 was time to discontinuation due to a mood event . RESULTS Patients were recruited between May 2004 and November 2008 . Following phase 1 , in which 96 patients received aripiprazole , 30 patients ( mean age = 7.1 years ) were r and omly assigned to continue aripiprazole and 30 patients ( mean age = 6.7 years ) were r and omly assigned to placebo . The mean ( SD ) dose of aripiprazole prior to r and omization for these patients was 6.4 ( 2.1 ) mg/d . Patients r and omly assigned to aripiprazole were enrolled significantly longer until time to study discontinuation due to a mood event ( 6.14 median weeks , SE ± 11.88 weeks ; P = .005 ) and discontinuation for any reason ( including mood events ) ( 4.00 median weeks , SE ± 3.91 weeks ; P = .003 ) than those r and omly assigned to placebo ( mood event , 2.29 median weeks , SE ± 0.38 weeks ; any reason , 2.00 median weeks , SE ± 0.31 weeks ) . Regardless of r and om assignment , both the aripiprazole and placebo groups showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks ( 15/30 [ 50 % ] for aripiprazole ; 27/30 [ 90 % ] for placebo ) , suggesting a possible nocebo effect ( ie , knowledge of possibly switching from active medication to placebo increasing concern about relapse ) . The most frequently reported adverse events during double-blind aripiprazole therapy included stomach pain ( n = 10 , 33 % ) , increased appetite ( n = 9 , 30 % ) , and headaches ( n = 9 , 30 % ) . CONCLUSIONS Despite the possibility of a nocebo effect , these results suggest that aripiprazole may be superior to placebo in the long-term treatment of pediatric patients following stabilization with open-label aripiprazole . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00194077 BACKGROUND Evidence is accumulating to support the use of atypical neuroleptics as adjunctive treatment for refractory mood disorders , although there are currently no published data on the efficacy of an atypical neuroleptic in treatment-resistant depression when a previous trial of drug from the same class has failed . The authors hypothesized that aripiprazole would be efficacious in augmenting antidepressant treatment in resistant patients with non-psychotic unipolar depression who had previously failed a trial of another atypical neuroleptic . METHODS This study was a retrospective chart review of the efficacy of aripiprazole augmentation in 30 treatment-resistant unipolar depression patients who had failed multiple previous antidepressant trials and had also failed augmentation with at least one other atypical neuroleptic .  Prospect i ve Global Assessment of Functioning and Clinical Global Impressions-Improvement scores were completed on each patient throughout treatment . RESULTS Utilizing an intent-to-treat analysis ( including 9 patients who dropped out prior to completion of 6 weeks ) , 46.7 % ( 14/30 ) patients were rated much improved or very much improved with treatment . This improvement negatively correlated with Thase-Rush staging of treatment resistance . GAF scores also showed a significant improvement . Six of the 14 patients who initially improved subsequently relapsed ( yielding a long-term net response rate of 26.7 % ) . CONCLUSION Aripiprazole may be effective as an antidepressant augmentation agent in highly treatment resistant patients who had failed a prior trial of another atypical neuroleptic OBJECTIVE This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions . METHODS Out patients , ages 7 - 17 years , meeting American Psychiatric Association , diagnostic and statistical manual of mental disorders , 4th ed . ( DSM-IV ) diagnostic criteria for bipolar disorder I ( BP-I ) ( manic or mixed ) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium ( phase I ) were eligible to receive open-label lithium for an additional 16 weeks ( phase II ) . Up to two adjunctive medications could be prescribed to patients experiencing residual symptoms of mania or comorbid psychiatric conditions , following a st and ardized algorithm . RESULTS Forty-one patients received continued open-label long-term treatment with lithium for a mean of 14.9 ( 3.0 ) weeks during phase II . The mean weight-adjusted total daily dose at end of phase II was 27.8 ( 6.7 ) mg/kg/day , with an average lithium concentration of 1.0 ( 0.3 ) mEq/L. Twenty-five of the 41 patients ( 60.9 % ) were prescribed adjunctive psychotropic medications for residual symptoms . The most frequent indications for adjunctive medications were refractory mania ( n=13 ; 31.7 % ) and attention-deficit/hyperactivity disorder ( ADHD ) ( n=15 ; 36.6 % ) . At the end of this phase 28 ( 68.3 % ) patients met a priori criteria for response ( ≥50 % reduction from phase I baseline in young mania rating scale [ YMRS ] summary score and a clinical global impressions-improvement [ CGI-I ] score of 1 or 2 ) , with 22 ( 53.7 % ) considered to be in remission ( YMRS summary score≤12 and CGI-severity score of 1 or 2 ) . These data suggest that patients who initially responded to lithium  maintained mood stabilization during continuation treatment , but partial responders did not experience further improvement during Phase II , despite the opportunity to receive adjunctive medications . The most commonly reported ( ≥20 % ) adverse events associated with lithium treatment were vomiting , headache , abdominal pain , and tremor .  CONCLUSIONS Lithium may be a safe and effective longer-term treatment for patients with pediatric bipolar disorder who respond to acute treatment with lithium . Partial responders to acute lithium did not appear to experience substantial symptom improvement during the continuation phase , despite the possibility that adjunctive medications could be prescribed OBJECTIVES To evaluate the efficacy , safety , and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder . METHODS This r and omized , placebo-controlled , double-blind , 3-arm study ( N = 169 ) included children and adolescents ( ages 10 - 17 years ) with a DSM-IV diagnosis of bipolar I disorder , experiencing a manic or mixed episode . Study participants were r and omized to placebo ( n = 58 ) , risperidone 0.5 - 2.5 mg/day ( n = 50 ) , or risper 
    Output:
    
agent
RESULTS There is sufficient evidence for a Grade A recommendation of the use of olanzapine plus fluoxetine at reducing depressive symptoms in bipolar depression and of quetiapine at high doses for depressive symptoms occurring during mixed episodes .
These results mostly overlap with the approved treatments for bipolar depression in adults
***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 treatment of pediatric bipolar depression has not been well studied . The authors wished to prospect ively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode . METHOD This was an 8-week open-label trial of lamotrigine with 20 adolescents ages 12 - 17 years ( mean age 15.8 ; 7 boys , 13 girls ) with diagnoses of bipolar disorder I , II , or not otherwise specified , who were experiencing a depressive episode .  Lamotrigine was begun at 12.5 to 25 mg/day . Primary response criteria was a 1 or a 2 on the Clinical Global Impression-Improvement at week 8 . A secondary criterion was at least a 50 % decrease in Children 's Depression Rating Scale-Revised scores . RESULTS Nineteen subjects completed the trial . The mean final dose was 131.6 mg/day . Seven subjects were taking other psychotropic medications . Sixteen subjects ( 84 % ) responded by primary criteria , and 12 ( 63 % ) responded to our secondary criteria . Eleven subjects ( 58 % ) were considered in remission at week 8 . Young Mania Rating Scale and Overt Aggression Scale-Modified scores also decreased significantly during the trial . There was no significant weight change , rash , or other adverse effects during the trial . CONCLUSIONS Adolescents with bipolar depression appeared to respond to lamotrigine treatment , whether as adjunctive therapy or monotherapy , with decreases in depression , mania , and aggression . Larger , placebo-controlled studies of lamotrigine are needed in this population BACKGROUND Antidepressant-induced mania ( AIM ) has been described in bipolar disorder ( BD ) and has been associated with the short-allele of the serotonin transporter gene ( 5-HTT ) . We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD . METHODS Fifty-two children and adolescents ( 30 with BD and 22 with subthreshold manic symptoms , 15.1 + /- 3.4 years old ) , all with a parent with BD , were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment .  The 47 subjects with serotonin reuptake inhibitor ( SSRI ) exposure  were genotyped for the 5-HTT polymorphism . RESULTS Fifty percent of subjects were AIM + and 25.5 % had new onset of suicidal ideation . The AIM + and AIM - groups did not differ significantly in relation to allele ( p = .36 ) or genotype ( p = .53 ) frequencies of the 5-HTT polymorphism . The AIM + subjects were more likely to have more comorbidities ( 3.2 vs. 2.4 ; p = .02 ) and be BD type I ( p = .04 ) than AIM - subjects . CONCLUSIONS Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs . In this preliminary study , we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM OBJECTIVE To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania . METHODS This was an eight-week , open-label , prospect i ve study of ziprasidone monotherapy ( 57.3 + /- 33.9 mg/day ) in 21 bipolar youth [ manic , mixed , or bipolar not otherwise specified ( NOS ) ; 6 - 17 years old ] . Assessment s included the Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions-Improvement scale ( CGI-I ) , and Brief Psychiatric Rating Scale ( BPRS ) . Adverse events were assessed through spontaneous self-reports , vital signs , weight monitoring , and laboratory analysis . RESULTS Fourteen of the 21 youth ( 67 % ) completed the study .  Ziprasidone treatment was associated with clinical ly and statistically significant improvement in mean YMRS scores ( -10.8 + /- 8.4 , p < 0.0001 ) and 57 % had a CGI-I < or=2 at endpoint . Ziprasidone was well tolerated with no statistically significant increase in body weight ( 0.6 + /- 0.4 kg , p = 0.2 ) or QTc interval ( -3.7 + /- 4.7 , p = 0.5 ) . CONCLUSIONS Open-label ziprasidone treatment was associated with a significant short-term improvement of symptoms of pediatric bipolar disorder . Future placebo-controlled , double-blind studies are warranted The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder . The third version is based explicitly on the available evidence and presented , like previous Clinical Practice Guidelines , as recommendations to aid clinical decision making for practitioners : it may also serve as a source of information for patients and carers , and assist audit . The recommendations are presented together with a more detailed review of the corresponding evidence . A consensus meeting , involving experts in bipolar disorder and its treatment , review ed key areas and considered the strength of evidence and clinical implication s. The guidelines were drawn up after extensive feedback from these participants . The best evidence from r and omized controlled trials and , where available , observational studies employing quasi-experimental design s was used to evaluate treatment options . The strength of recommendations has been described using the GRADE approach . The guidelines cover the diagnosis of bipolar disorder , clinical management , and strategies for the use of medicines in short-term treatment of episodes , relapse prevention and stopping treatment . The use of medication is integrated with a coherent approach to psychoeducation and behaviour change BACKGROUND This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders . METHOD Out patients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder ( I , II , not otherwise specified , cyclothymia ) were eligible to receive up to 16 weeks of open-label treatment with  aripiprazole ( phase 1 ) . Patients were r and omized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization ( phase 2 ) . During phase 2 , patients either remained on their current aripiprazole regimen or began a double-blind taper with aripiprazole discontinued and switched to placebo . The primary outcome measure for phase 2 was time to discontinuation due to a mood event . RESULTS Patients were recruited between May 2004 and November 2008 . Following phase 1 , in which 96 patients received aripiprazole , 30 patients ( mean age = 7.1 years ) were r and omly assigned to continue aripiprazole and 30 patients ( mean age = 6.7 years ) were r and omly assigned to placebo . The mean ( SD ) dose of aripiprazole prior to r and omization for these patients was 6.4 ( 2.1 ) mg/d . Patients r and omly assigned to aripiprazole were enrolled significantly longer until time to study discontinuation due to a mood event ( 6.14 median weeks , SE ± 11.88 weeks ; P = .005 ) and discontinuation for any reason ( including mood events ) ( 4.00 median weeks , SE ± 3.91 weeks ; P = .003 ) than those r and omly assigned to placebo ( mood event , 2.29 median weeks , SE ± 0.38 weeks ; any reason , 2.00 median weeks , SE ± 0.31 weeks ) . Regardless of r and om assignment , both the aripiprazole and placebo groups showed substantial rates of withdrawal from maintenance treatment over the initial 4 weeks ( 15/30 [ 50 % ] for aripiprazole ; 27/30 [ 90 % ] for placebo ) , suggesting a possible nocebo effect ( ie , knowledge of possibly switching from active medication to placebo increasing concern about relapse ) . The most frequently reported adverse events during double-blind aripiprazole therapy included stomach pain ( n = 10 , 33 % ) , increased appetite ( n = 9 , 30 % ) , and headaches ( n = 9 , 30 % ) . CONCLUSIONS Despite the possibility of a nocebo effect , these results suggest that aripiprazole may be superior to placebo in the long-term treatment of pediatric patients following stabilization with open-label aripiprazole . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00194077 BACKGROUND Evidence is accumulating to support the use of atypical neuroleptics as adjunctive treatment for refractory mood disorders , although there are currently no published data on the efficacy of an atypical neuroleptic in treatment-resistant depression when a previous trial of drug from the same class has failed . The authors hypothesized that aripiprazole would be efficacious in augmenting antidepressant treatment in resistant patients with non-psychotic unipolar depression who had previously failed a trial of another atypical neuroleptic . METHODS This study was a retrospective chart review of the efficacy of aripiprazole augmentation in 30 treatment-resistant unipolar depression patients who had failed multiple previous antidepressant trials and had also failed augmentation with at least one other atypical neuroleptic .  Prospect i ve Global Assessment of Functioning and Clinical Global Impressions-Improvement scores were completed on each patient throughout treatment . RESULTS Utilizing an intent-to-treat analysis ( including 9 patients who dropped out prior to completion of 6 weeks ) , 46.7 % ( 14/30 ) patients were rated much improved or very much improved with treatment . This improvement negatively correlated with Thase-Rush staging of treatment resistance . GAF scores also showed a significant improvement . Six of the 14 patients who initially improved subsequently relapsed ( yielding a long-term net response rate of 26.7 % ) . CONCLUSION Aripiprazole may be effective as an antidepressant augmentation agent in highly treatment resistant patients who had failed a prior trial of another atypical neuroleptic OBJECTIVE This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions . METHODS Out patients , ages 7 - 17 years , meeting American Psychiatric Association , diagnostic and statistical manual of mental disorders , 4th ed . ( DSM-IV ) diagnostic criteria for bipolar disorder I ( BP-I ) ( manic or mixed ) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium ( phase I ) were eligible to receive open-label lithium for an additional 16 weeks ( phase II ) . Up to two adjunctive medications could be prescribed to patients experiencing residual symptoms of mania or comorbid psychiatric conditions , following a st and ardized algorithm . RESULTS Forty-one patients received continued open-label long-term treatment with lithium for a mean of 14.9 ( 3.0 ) weeks during phase II . The mean weight-adjusted total daily dose at end of phase II was 27.8 ( 6.7 ) mg/kg/day , with an average lithium concentration of 1.0 ( 0.3 ) mEq/L. Twenty-five of the 41 patients ( 60.9 % ) were prescribed adjunctive psychotropic medications for residual symptoms . The most frequent indications for adjunctive medications were refractory mania ( n=13 ; 31.7 % ) and attention-deficit/hyperactivity disorder ( ADHD ) ( n=15 ; 36.6 % ) . At the end of this phase 28 ( 68.3 % ) patients met a priori criteria for response ( ≥50 % reduction from phase I baseline in young mania rating scale [ YMRS ] summary score and a clinical global impressions-improvement [ CGI-I ] score of 1 or 2 ) , with 22 ( 53.7 % ) considered to be in remission ( YMRS summary score≤12 and CGI-severity score of 1 or 2 ) . These data suggest that patients who initially responded to lithium  maintained mood stabilization during continuation treatment , but partial responders did not experience further improvement during Phase II , despite the opportunity to receive adjunctive medications . The most commonly reported ( ≥20 % ) adverse events associated with lithium treatment were vomiting , headache , abdominal pain , and tremor .  CONCLUSIONS Lithium may be a safe and effective longer-term treatment for patients with pediatric bipolar disorder who respond to acute treatment with lithium . Partial responders to acute lithium did not appear to experience substantial symptom improvement during the continuation phase , despite the possibility that adjunctive medications could be prescribed OBJECTIVES To evaluate the efficacy , safety , and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder . METHODS This r and omized , placebo-controlled , double-blind , 3-arm study ( N = 169 ) included children and adolescents ( ages 10 - 17 years ) with a DSM-IV diagnosis of bipolar I disorder , experiencing a manic or mixed episode . Study participants were r and omized to placebo ( n = 58 ) , risperidone 0.5 - 2.5 mg/day ( n = 50 ) , or risper 
    Output:
    