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: 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 OBJECTIVE This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics , such as the presence of a mixed affective state , might predict a differential response to the two drugs . METHOD Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week , r and omized , double-blind , parallel-groups trial of treatment with lithium carbonate or valproate .  Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia , change version ( SADS-C ) , the Global Assessment Scale ( GAS ) , and the Brief Psychiatric Rating Scale ( BPRS ) . Drug effects were compared by using repeated measures analysis of variance ( ANOVA ) . RESULTS At the end of the study , nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably , as measured by changes in the SADS-C mania , BPRS , and GAS scores . Elevated pretreatment SADS-C depression scores were associated with good response to valproate . ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response . CONCLUSIONS Lithium and valproate were both effective in improving manic symptoms , and lithium was slightly more efficacious overall . Unlike the case with lithium , favorable response to valproate was associated with high pretreatment depression scores . Therefore , treatment with valproate alone may be particularly effective in manic patients with mixed affective states In an 18-hospital collaborative study , 255 newly admitted manic patients were r and omly assigned to lithium carbonate or chlorpromazine for a three-week period . Patients were classified as highly active or mildly active on the basis of degree of motor activity shown at admission . Treatments were compared in terms of early terminations , symptom change , and toxicity . The following results were obtained : ( 1 ) Chlorpromazine was clearly superior to lithium carbonate in treating the highly active patient . Chlorpromazine acted more quickly , produced significantly fewer dropouts , and had a lower incidence of severe side effects . ( 2 ) The difference between lithium carbonate and chlorpromazine was less pronounced among mildly active patients . Lithium carbonate , however , appeared to be the better treatment . Both drugs effectively reduced manic symptomatology but lithium carbonate left the patient feeling less sluggish and fatigued .  Lithium carbonate also produced fewer severe side effects than chlorpromazine Two drug trials in schizoaffective patients are reported . Nineteen " schizomanic " patients were treated for one month , on a double blind basis , with chlorpromazine or lithium and 41 " schizodepressive " patients with amitriptyline , chlorpromazine or both . In the schizodepressive patients there was a trend to a better response to chlorpromazine , but drug response generally was poor , only 20 per cent of patients recovering within the month . In the schizomanic patients lithium seemed as effective as chlorpromazine , which supports the view that these patients were suffering from a variant of mania The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode . This international , r and omized , open-label , parallel-group , equivalence study included 268 patients with bipolar I disorder . The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day . Treatment duration was 12 weeks . The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end . Secondary outcome measures were response and remission rates , change in Montgomery and Åsberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score , and occurrence of adverse events . The mean change from baseline in Young Mania Rating Scale score was 15.8±5.3 in the lithium group and 17.3±9.4 in the valproate group . The 90 % confidence interval of the intergroup difference ( −0.69 ; 3.31 ) was within prespecified equivalence limits . Response rates were 72.6 % in the lithium group and 79.5 % in the valproate  group . Remission rates were 58.5 and 71.9 % , respectively . No intergroup differences were observed in median time to treatment response ( 21 days ) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Åsberg Depression Rating Scale scores . Adverse events were reported in 42.8 % of patients in the lithium group and 41.5 % in the valproate group . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks Sulpiride , in this open study of acute manic patients , had a clear antimanic action with all eight patients responding to sulpiride treatment without the need for other antipsychotic drugs . Plasma prolactin concentrations were increased and oestrogen-stimulated neurophysin concentrations decreased by sulpiride but were unchanged by lithium treatment , whereas TSH concentrations showed a rapid increase following the introduction of lithium therapy Previous investigations of the treatment of mania have result ed in uncertainty about the efficacy of lithium versus a neuroleptic . In addition there have been reports of toxicity with a haloperidol -- lithium combination . In order to determine the comparative efficacy of lithium vs haloperidol vs a combination of haloperidol -- lithium , we studied 21 severely ill manic patients who all met rigorous criteria for bipolar illness and who required in hospital treatment . Subjects were r and omly assigned to 3 groups : ( A ) Lithium plus placebo ( B ) Placebo plus haloperidol and ( C ) Lithium plus haloperidol . The study was conducted in double blind fashion for 3 weeks with the dosages of the medications varied according to clinical response or untoward effects . Subjects on haloperidol and placebo or the haloperidol -- lithium combination were significantly improved after 7 days in comparison to the lithium-treated group . Groups B and C did not differ from each other , either in degree of improvement or in side effects . Inspite of the relatively small sample size the results suggest ( 1 ) that haloperidol is superior to lithium for treating severely ill acute mania and ( 2 ) that while a haloperidol -- lithium combination does not result in a significant increase in side effects , it is not superior to haloperidol alone OBJECTIVE To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder . METHOD In an international , multicenter , double-blind , parallel-group , 12-week study , patients with a DSM-IV diagnosis of bipolar I disorder ( manic episode ) were r and omly assigned to treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or lithium . The primary efficacy measure was change from baseline in Young Mania Rating Scale ( YMRS ) score at day 21 . Data were gathered from April 2001 to May 2002 . RESULTS More patients in the quetiapine ( 72/107 ) and lithium ( 67/98 ) groups completed the study compared with the placebo group ( 35/97 ) . Improvement ( reduction ) in YMRS score was significantly greater for quetiapine than placebo at day 7 ( -8.03 vs. -4.89 ; p < .01 ) , and the difference between groups continued to increase over time to day 21 ( -14.6 vs. -6.7 ; p < .001 ) and to endpoint at day 84 ( -20.3 vs. -9.0 ; p < .001 ) . Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 ( 53.3 % vs. 27.4 % ; p < .001 ) and at day 84 ( 72.0 % vs. 41.1 % ; p < .001 ) . Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures . Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure . The most common adverse events for quetiapine were dry mouth , somnolence , and weight gain , while lithium was associated with tremor and insomnia . The quetiapine and placebo groups had similar , low levels of extrapyramidal symptom-related adverse events . CONCLUSIONS Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated Lithium carbonate , haloperidol , and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics .  Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation . Although producing considerable sedation , chlorpromazine did little to alter the underlying mania qualitatively . Qualitative differences between lithium carbonate and haloperidol indicate that , while haloperidol has a more dramatically rapid impact on behavior-motor activity , lithium carbonate acted more evenly on the entire manic picture , with total normalization realized during active treatment . The majority of lithium carbonate-treated patients met discharge criteria at study termination , but not the patients receiving either neuroleptic drug . The rating scales are not sensitive enough to monitor manic psychopathology ; this accounts for the lack of statistically significant differences among drug groups at treatment termination , despite the widely disparate discharge rates On the basis of 3-week studies , lithium and valproate are both recommended for first-line treatment of acute mania . It is , however , also important to demonstrate that antimanic efficacy can be maintained . This study has been design ed to compare the efficacy and tolerability of valproate and lithium over 12 weeks in the treatment of acute mania in patients with type I bipolar disorder . Three hundred patients with bipolar I disorder presenting with acute mania were r and omized to open treatment with lithium ( starting dose : 400 mg/day ) or valproate ( starting dose : 20 mg/kg/day ) for 12 weeks . The primary efficacy criterion was remission ( YMRS score ≤12 at study end and a reduction of ≥2 on the CGI-BP severity scale ) . Remission rates were 65.5 % ( lithium group ) and 72.3 % ( valproate  group ) . Noninferiority  of  valproate with respect to lithium was demonstrated [ between-group difference : 6.78 % ( 95 % confidence intervals : −3.80 to 17.36 % ) ] . Remission rates assessed by the secondary mixed model repeated measures analysis were significantly greater with valproate than with lithium . Adverse events were reported in 44 % of patients in both  groups . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks For the treatment of acute mania , no single drug is sufficiently effective in daily clinical routine for all patients . Drug combinations are often prescribed but poorly investigated . The present study examined whether a treatment with a neuroleptic drug ( zuclopenthixol ) combined with a benzodiazepine ( clonazepam ) was superior to a treatment with lithium and the same benzodiazepine ( lithium citrate and clonazepam ) .  Twenty‐eight hospitalized patients with a DSM‐III‐R manic episode were included , r and omized to fixed drug doses and observed up to 28 days . Degree of mania , side effects and patients satisfaction with the treatment were registered . Approximately two thirds of the patients improved fully or partially on both drug combinations . Furthermore no statistically significant differences were found regarding acceptance and tolerance of the two drug combinations . The present drug combination are only two among several which deserve a thorough examination in order to prevent a r and om polypharmacy for treatment of mania ABSTRACT Objective : To assess the efficacy and tolerability of quetiapine in Chinese patients hospitalized with acute bipolar mania . Methods : This was a 4-week , multicenter , r and omized , double-blind , lithium-controlled , parallel-group study . Secondary endpoints in the primary analysis were : response rate ( ≥ 50 % decrease from baseline in YMRS total score ) and remission rate as defined using 3 criteria : YMRS total score ≤ 12 , YMRS total score ≤ 12 + MADRS total score ≤ 8 , and YMRS total score ≤ 8 . Other measures included : change from baseline at Day 28 in YMRS , PANSS , and MADRS total score . Adverse event ( AE ) data were collected throughout the study . Results : 73 ( 94.8 % 
    Output:
    
agent
This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor .
Limited evidence suggests little or no difference between lithium and other mood stabilisers ( valproate , carbamazepine ) or antipsychotics ( risperidone , quetiapine , haloperidol ) .
Olanzapine may be an exception , as it is probably slightly more effective than lithium .
There is uncertain evidence that risperidone may also be more effective than lithium .
Lithium is probably more effective at treating acute mania than topiramate .
When compared to placebo , lithium was more likely to cause adverse events .
More , rigorously design ed , large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania
***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: 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 OBJECTIVE This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics , such as the presence of a mixed affective state , might predict a differential response to the two drugs . METHOD Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week , r and omized , double-blind , parallel-groups trial of treatment with lithium carbonate or valproate .  Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia , change version ( SADS-C ) , the Global Assessment Scale ( GAS ) , and the Brief Psychiatric Rating Scale ( BPRS ) . Drug effects were compared by using repeated measures analysis of variance ( ANOVA ) . RESULTS At the end of the study , nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably , as measured by changes in the SADS-C mania , BPRS , and GAS scores . Elevated pretreatment SADS-C depression scores were associated with good response to valproate . ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response . CONCLUSIONS Lithium and valproate were both effective in improving manic symptoms , and lithium was slightly more efficacious overall . Unlike the case with lithium , favorable response to valproate was associated with high pretreatment depression scores . Therefore , treatment with valproate alone may be particularly effective in manic patients with mixed affective states In an 18-hospital collaborative study , 255 newly admitted manic patients were r and omly assigned to lithium carbonate or chlorpromazine for a three-week period . Patients were classified as highly active or mildly active on the basis of degree of motor activity shown at admission . Treatments were compared in terms of early terminations , symptom change , and toxicity . The following results were obtained : ( 1 ) Chlorpromazine was clearly superior to lithium carbonate in treating the highly active patient . Chlorpromazine acted more quickly , produced significantly fewer dropouts , and had a lower incidence of severe side effects . ( 2 ) The difference between lithium carbonate and chlorpromazine was less pronounced among mildly active patients . Lithium carbonate , however , appeared to be the better treatment . Both drugs effectively reduced manic symptomatology but lithium carbonate left the patient feeling less sluggish and fatigued .  Lithium carbonate also produced fewer severe side effects than chlorpromazine Two drug trials in schizoaffective patients are reported . Nineteen " schizomanic " patients were treated for one month , on a double blind basis , with chlorpromazine or lithium and 41 " schizodepressive " patients with amitriptyline , chlorpromazine or both . In the schizodepressive patients there was a trend to a better response to chlorpromazine , but drug response generally was poor , only 20 per cent of patients recovering within the month . In the schizomanic patients lithium seemed as effective as chlorpromazine , which supports the view that these patients were suffering from a variant of mania The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode . This international , r and omized , open-label , parallel-group , equivalence study included 268 patients with bipolar I disorder . The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day . Treatment duration was 12 weeks . The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end . Secondary outcome measures were response and remission rates , change in Montgomery and Åsberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score , and occurrence of adverse events . The mean change from baseline in Young Mania Rating Scale score was 15.8±5.3 in the lithium group and 17.3±9.4 in the valproate group . The 90 % confidence interval of the intergroup difference ( −0.69 ; 3.31 ) was within prespecified equivalence limits . Response rates were 72.6 % in the lithium group and 79.5 % in the valproate  group . Remission rates were 58.5 and 71.9 % , respectively . No intergroup differences were observed in median time to treatment response ( 21 days ) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Åsberg Depression Rating Scale scores . Adverse events were reported in 42.8 % of patients in the lithium group and 41.5 % in the valproate group . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks Sulpiride , in this open study of acute manic patients , had a clear antimanic action with all eight patients responding to sulpiride treatment without the need for other antipsychotic drugs . Plasma prolactin concentrations were increased and oestrogen-stimulated neurophysin concentrations decreased by sulpiride but were unchanged by lithium treatment , whereas TSH concentrations showed a rapid increase following the introduction of lithium therapy Previous investigations of the treatment of mania have result ed in uncertainty about the efficacy of lithium versus a neuroleptic . In addition there have been reports of toxicity with a haloperidol -- lithium combination . In order to determine the comparative efficacy of lithium vs haloperidol vs a combination of haloperidol -- lithium , we studied 21 severely ill manic patients who all met rigorous criteria for bipolar illness and who required in hospital treatment . Subjects were r and omly assigned to 3 groups : ( A ) Lithium plus placebo ( B ) Placebo plus haloperidol and ( C ) Lithium plus haloperidol . The study was conducted in double blind fashion for 3 weeks with the dosages of the medications varied according to clinical response or untoward effects . Subjects on haloperidol and placebo or the haloperidol -- lithium combination were significantly improved after 7 days in comparison to the lithium-treated group . Groups B and C did not differ from each other , either in degree of improvement or in side effects . Inspite of the relatively small sample size the results suggest ( 1 ) that haloperidol is superior to lithium for treating severely ill acute mania and ( 2 ) that while a haloperidol -- lithium combination does not result in a significant increase in side effects , it is not superior to haloperidol alone OBJECTIVE To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder . METHOD In an international , multicenter , double-blind , parallel-group , 12-week study , patients with a DSM-IV diagnosis of bipolar I disorder ( manic episode ) were r and omly assigned to treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or lithium . The primary efficacy measure was change from baseline in Young Mania Rating Scale ( YMRS ) score at day 21 . Data were gathered from April 2001 to May 2002 . RESULTS More patients in the quetiapine ( 72/107 ) and lithium ( 67/98 ) groups completed the study compared with the placebo group ( 35/97 ) . Improvement ( reduction ) in YMRS score was significantly greater for quetiapine than placebo at day 7 ( -8.03 vs. -4.89 ; p < .01 ) , and the difference between groups continued to increase over time to day 21 ( -14.6 vs. -6.7 ; p < .001 ) and to endpoint at day 84 ( -20.3 vs. -9.0 ; p < .001 ) . Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 ( 53.3 % vs. 27.4 % ; p < .001 ) and at day 84 ( 72.0 % vs. 41.1 % ; p < .001 ) . Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures . Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure . The most common adverse events for quetiapine were dry mouth , somnolence , and weight gain , while lithium was associated with tremor and insomnia . The quetiapine and placebo groups had similar , low levels of extrapyramidal symptom-related adverse events . CONCLUSIONS Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated Lithium carbonate , haloperidol , and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics .  Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation . Although producing considerable sedation , chlorpromazine did little to alter the underlying mania qualitatively . Qualitative differences between lithium carbonate and haloperidol indicate that , while haloperidol has a more dramatically rapid impact on behavior-motor activity , lithium carbonate acted more evenly on the entire manic picture , with total normalization realized during active treatment . The majority of lithium carbonate-treated patients met discharge criteria at study termination , but not the patients receiving either neuroleptic drug . The rating scales are not sensitive enough to monitor manic psychopathology ; this accounts for the lack of statistically significant differences among drug groups at treatment termination , despite the widely disparate discharge rates On the basis of 3-week studies , lithium and valproate are both recommended for first-line treatment of acute mania . It is , however , also important to demonstrate that antimanic efficacy can be maintained . This study has been design ed to compare the efficacy and tolerability of valproate and lithium over 12 weeks in the treatment of acute mania in patients with type I bipolar disorder . Three hundred patients with bipolar I disorder presenting with acute mania were r and omized to open treatment with lithium ( starting dose : 400 mg/day ) or valproate ( starting dose : 20 mg/kg/day ) for 12 weeks . The primary efficacy criterion was remission ( YMRS score ≤12 at study end and a reduction of ≥2 on the CGI-BP severity scale ) . Remission rates were 65.5 % ( lithium group ) and 72.3 % ( valproate  group ) . Noninferiority  of  valproate with respect to lithium was demonstrated [ between-group difference : 6.78 % ( 95 % confidence intervals : −3.80 to 17.36 % ) ] . Remission rates assessed by the secondary mixed model repeated measures analysis were significantly greater with valproate than with lithium . Adverse events were reported in 44 % of patients in both  groups . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks For the treatment of acute mania , no single drug is sufficiently effective in daily clinical routine for all patients . Drug combinations are often prescribed but poorly investigated . The present study examined whether a treatment with a neuroleptic drug ( zuclopenthixol ) combined with a benzodiazepine ( clonazepam ) was superior to a treatment with lithium and the same benzodiazepine ( lithium citrate and clonazepam ) .  Twenty‐eight hospitalized patients with a DSM‐III‐R manic episode were included , r and omized to fixed drug doses and observed up to 28 days . Degree of mania , side effects and patients satisfaction with the treatment were registered . Approximately two thirds of the patients improved fully or partially on both drug combinations . Furthermore no statistically significant differences were found regarding acceptance and tolerance of the two drug combinations . The present drug combination are only two among several which deserve a thorough examination in order to prevent a r and om polypharmacy for treatment of mania ABSTRACT Objective : To assess the efficacy and tolerability of quetiapine in Chinese patients hospitalized with acute bipolar mania . Methods : This was a 4-week , multicenter , r and omized , double-blind , lithium-controlled , parallel-group study . Secondary endpoints in the primary analysis were : response rate ( ≥ 50 % decrease from baseline in YMRS total score ) and remission rate as defined using 3 criteria : YMRS total score ≤ 12 , YMRS total score ≤ 12 + MADRS total score ≤ 8 , and YMRS total score ≤ 8 . Other measures included : change from baseline at Day 28 in YMRS , PANSS , and MADRS total score . Adverse event ( AE ) data were collected throughout the study . Results : 73 ( 94.8 % 
    Output:
    