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: BACKGROUND The effectiveness of antipsychotic monotherapy in  schizoaffective disorder  is limited , and further constrained by safety concerns . AIMS We aim ed to compare the efficacy , tolerability and safety profile of the new pharmaceutical , olanzapine , with haloperidol . METHOD Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospect i ve international study . Subjects were r and omly allocated to six weeks of olanzapine ( 5 - 20 mg ) or haloperidol ( 5 - 20 mg ) treatment ; responders were followed for up to one year of double-blind , long-term maintenance therapy . RESULTS Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy , including clinical response . Significantly fewer olanzapine patients left the study early , and fewer adverse events were observed among those receiving olanzapine . During maintenance , olanzapine-treated patients continued to experience additional improvement , with fewer EPS but more weight gain than those on haloperidol . CONCLUSIONS Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder Background : Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships , as well as work performance . We report the results of a multicenter , r and omized , placebo-controlled trial comparing the efficacy , safety , and tolerability of fluvoxamine controlled release ( CR ) to placebo in patients with generalized social anxiety disorder . Methods : A total of 279 adult patients meeting all inclusion /exclusion criteria was recruited at 23 United States sites and r and omly assigned to receive either fluvoxamine CR ( 100 - 200 mg/d ) or placebo for 12 weeks . The dose could be increased , based on efficacy and tolerability , in increments of 50 mg/d at weekly intervals . The dosage remained constant during weeks 6 to 12 . Results : Treatment with fluvoxamine CR result ed in statistically and clinical ly significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement , and at week 6 on the Sheehan Disability Scale , Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale . The most frequent adverse events reported by patients on fluvoxamine CR were headache , nausea , somnolence , and insomnia . No weight gain was observed for either treatment group , and at end point , there were no differences between treatments on overall sexual function , as measured by the Arizona Sexual Experience Scale . Conclusions : Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder PURPOSE Previous analysis of data from CATIE showed that patients r and omly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to r and omization . This study addresses additional outcomes measures evaluating symptoms , neurocognition , quality of life , neurological side effects , weight , and health costs . First , considering patients r and omized to olanzapine or risperidone  , outcomes among patients who had been on the drug to which they were r and omized prior to CATIE ( N=129 " stayers " ) were compared to outcomes of those who switched to either of these two drugs ( N=269 " switchers " ) . A second set of analyses considered patients on baseline monotherapy with olanzapine ( N=297 ) ; risperidone ( N=252 ) or quetiapine ( n=87 ) and compared those r and omly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE . In mixed models of each outcome the independent variable of primary interest represented stay vs. switch , with multivariate adjustment for potential confounding factors . RESULTS With one exception , there were no significant differences between stayers and switchers on any outcome measure in either set of analyses . The exception was that , in the second set of analyses , patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs . CONCLUSION Switching to a new medication yielded no advantage over staying on the previous medication . Staying on olanzapine was associated with greater weight gain 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 BACKGROUND Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine , vertigo , and cognitive deficits related to cerebrovascular disorders . Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics . However , its clinical antipsychotic efficacy has never been investigated . OBJECTIVE To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in out patients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder . METHOD Seventy patients from 2 centers were r and omly assigned and participated in a double-blind , parallel-group , flexible-dose study comparing flunarizine ( 10 - 50 mg/day ) and haloperidol ( 2.5 - 12.5 mg/day ) for 12 weeks . Patients were assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Improvement ( CGI-I ) scale , the Extrapyramidal Symptom Rating Scale ( ESRS ) , a battery for cognitive performance , and laboratory examinations . The study was conducted from September 2004 to May 2007 . RESULTS Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol . Both groups showed significant symptom improvement during the study , with a reduction of 21 % in the flunarizine group and 19 % in the haloperidol group in PANSS total scores ( p < .05 ) . There were no significant differences in PANSS overall score and all subscales , CGI-I score , or cognitive performance . Dropout rates , ESRS scores , and prolactin levels were not different between groups , but significantly more patients reported emergence of akathisia in the haloperidol group ( p = .04 ) , and weight gain was significantly higher with flunarizine ( 1.2 kg ) than with haloperidol ( -0.8 kg ) ( p < .05 ) . CONCLUSION This is the first study evaluating the antipsychotic properties of flunarizine , which showed good efficacy and tolerability for the treatment of schizophrenia , with a possible atypical profile . Its unique pharmacokinetic profile as an oral drug with long half-life ( 2 - 7 weeks ) , low cost , and low induction of extrapyramidal symptoms warrants further investigation , particularly in psychiatric patients with low adherence to treatment OBJECTIVE The goal of this 5-year naturalistic study of patients treated with clozapine  was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors , including weight gain , lipid abnormalities , age , clozapine dose , and treatment with valproate . METHOD Data on age , gender , race , diagnosis , family history of diabetes , and age at clozapine initiation were collected from medical records of 82 out patients with schizophrenia or schizoaffective disorder .  Clozapine dose , data on use of valproate , and laboratory test results were recorded at 6-month intervals . RESULTS The mean age at the time of clozapine initiation of the 82 patients was 36.4 years ; 26.8 % of the patients were women , and 91.5 % were Caucasian . The mean baseline weight was 175.5 lb , and the mean body mass index was 26.9 kg/m(2 ) . Thirty patients ( 36.6 % ) were diagnosed with diabetes during the 5-year follow-up . Weight gain , use of valproate , and total daily dose of clozapine  were not significant risk factors for developing diabetes mellitus . Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine . There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level . CONCLUSIONS The results support the hypotheses that patients treated with clozapine  experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes BACKGROUND Carbamazepine is frequently used for treating bipolar disorder , but few large trials have assessed its efficacy in preventing relapse . We evaluated open-label monotherapy with beaded extended-release carbamazepine capsules ( ERC-CBZ ; SPD417 ) as continuation and short-term maintenance therapy in bipolar disorder patients with manic and mixed episodes . METHOD A 6-month , open-label study enrolled 92 patients with DSM-IV bipolar disorder ( most recent episode : 67 % [ N = 62 ] mixed , 33 % [ N = 30 ] manic ) who had participated in 2 previous 3-week , double-blind , placebo-controlled studies . Subjects received beaded ERC-CBZ ( 200 - 1600 mg/day ) , titrated at investigators ' discretion to a final mean dose of 938 mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary efficacy measure was time to relapse , and secondary efficacy measures included Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions scale ( CGI ) , and Hamilton Rating Scale for Depression ( HAM-D ) scores . Data were gathered from January 2000 to January 2002 . RESULTS Of 77 patients analyzed in the intent-to-treat population , 11 ( 14.3 % ) relapsed . Fifty-three patients ( 68.8 % ) discontinued early , including 18 ( 23.4 % ) due to adverse events . Observed mean time to relapse was 61.1 days , while estimated mean time to relapse based on the Kaplan-Meier model was 141.8 days . Improvements on the YMRS , CGI , and HAM-D from the beginning of prior double-blind treatment were maintained . The most common adverse events were headache , dizziness , and rash . No significant weight gain was noted . CONCLUSION We noted a low relapse rate with beaded ERC-CBZ in this 6-month trial . Adverse events were generally mild to moderate and were typical of those associated with carbamazepine . Controlled studies are warranted to further explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder A double-blind controlled study comparing the effects of bupropion to doxepin in out patients with primary depression was conducted to evaluate efficacy and safety differences between the two drugs . Following a 7-day placebo washout period , patients could be treated for up to 13 weeks on either treatment . Antidepressant response was assessed by the Hamilton Depression and Anxiety Scales , Clinical Global Severity and Improvement Ratings , and the Zung Self-Rating Depression Scale . Comparable efficacy between the compounds was found across the 13-week study . Doxepin differed from bupropion mainly on the sleep factor of the Hamilton Depression Scale , with doxepin improving sleep to a greater extent than bupropion . Doxepin produced a greater incidence of anticholinergic side effects , including dry mouth , constipation , sleepiness , and tiredness , in comparison to bupropion . Also , increased appetite and weight gain were consistent side effects of doxepin relative to bupropion OBJECTIVE The authors ' goal was to compare the efficacy and tolerability of 6 months ' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or 
    Output:
    
agent
We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts .
There were few discrepancies between published evidence and the expert panel in ranking these drugs .
Conclusion Potential for weight gain is an important consideration in choice of any psychotropic .
This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices
***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 The effectiveness of antipsychotic monotherapy in  schizoaffective disorder  is limited , and further constrained by safety concerns . AIMS We aim ed to compare the efficacy , tolerability and safety profile of the new pharmaceutical , olanzapine , with haloperidol . METHOD Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospect i ve international study . Subjects were r and omly allocated to six weeks of olanzapine ( 5 - 20 mg ) or haloperidol ( 5 - 20 mg ) treatment ; responders were followed for up to one year of double-blind , long-term maintenance therapy . RESULTS Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy , including clinical response . Significantly fewer olanzapine patients left the study early , and fewer adverse events were observed among those receiving olanzapine . During maintenance , olanzapine-treated patients continued to experience additional improvement , with fewer EPS but more weight gain than those on haloperidol . CONCLUSIONS Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder Background : Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships , as well as work performance . We report the results of a multicenter , r and omized , placebo-controlled trial comparing the efficacy , safety , and tolerability of fluvoxamine controlled release ( CR ) to placebo in patients with generalized social anxiety disorder . Methods : A total of 279 adult patients meeting all inclusion /exclusion criteria was recruited at 23 United States sites and r and omly assigned to receive either fluvoxamine CR ( 100 - 200 mg/d ) or placebo for 12 weeks . The dose could be increased , based on efficacy and tolerability , in increments of 50 mg/d at weekly intervals . The dosage remained constant during weeks 6 to 12 . Results : Treatment with fluvoxamine CR result ed in statistically and clinical ly significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement , and at week 6 on the Sheehan Disability Scale , Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale . The most frequent adverse events reported by patients on fluvoxamine CR were headache , nausea , somnolence , and insomnia . No weight gain was observed for either treatment group , and at end point , there were no differences between treatments on overall sexual function , as measured by the Arizona Sexual Experience Scale . Conclusions : Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder PURPOSE Previous analysis of data from CATIE showed that patients r and omly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to r and omization . This study addresses additional outcomes measures evaluating symptoms , neurocognition , quality of life , neurological side effects , weight , and health costs . First , considering patients r and omized to olanzapine or risperidone  , outcomes among patients who had been on the drug to which they were r and omized prior to CATIE ( N=129 " stayers " ) were compared to outcomes of those who switched to either of these two drugs ( N=269 " switchers " ) . A second set of analyses considered patients on baseline monotherapy with olanzapine ( N=297 ) ; risperidone ( N=252 ) or quetiapine ( n=87 ) and compared those r and omly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE . In mixed models of each outcome the independent variable of primary interest represented stay vs. switch , with multivariate adjustment for potential confounding factors . RESULTS With one exception , there were no significant differences between stayers and switchers on any outcome measure in either set of analyses . The exception was that , in the second set of analyses , patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs . CONCLUSION Switching to a new medication yielded no advantage over staying on the previous medication . Staying on olanzapine was associated with greater weight gain 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 BACKGROUND Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine , vertigo , and cognitive deficits related to cerebrovascular disorders . Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics . However , its clinical antipsychotic efficacy has never been investigated . OBJECTIVE To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in out patients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder . METHOD Seventy patients from 2 centers were r and omly assigned and participated in a double-blind , parallel-group , flexible-dose study comparing flunarizine ( 10 - 50 mg/day ) and haloperidol ( 2.5 - 12.5 mg/day ) for 12 weeks . Patients were assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Improvement ( CGI-I ) scale , the Extrapyramidal Symptom Rating Scale ( ESRS ) , a battery for cognitive performance , and laboratory examinations . The study was conducted from September 2004 to May 2007 . RESULTS Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol . Both groups showed significant symptom improvement during the study , with a reduction of 21 % in the flunarizine group and 19 % in the haloperidol group in PANSS total scores ( p < .05 ) . There were no significant differences in PANSS overall score and all subscales , CGI-I score , or cognitive performance . Dropout rates , ESRS scores , and prolactin levels were not different between groups , but significantly more patients reported emergence of akathisia in the haloperidol group ( p = .04 ) , and weight gain was significantly higher with flunarizine ( 1.2 kg ) than with haloperidol ( -0.8 kg ) ( p < .05 ) . CONCLUSION This is the first study evaluating the antipsychotic properties of flunarizine , which showed good efficacy and tolerability for the treatment of schizophrenia , with a possible atypical profile . Its unique pharmacokinetic profile as an oral drug with long half-life ( 2 - 7 weeks ) , low cost , and low induction of extrapyramidal symptoms warrants further investigation , particularly in psychiatric patients with low adherence to treatment OBJECTIVE The goal of this 5-year naturalistic study of patients treated with clozapine  was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors , including weight gain , lipid abnormalities , age , clozapine dose , and treatment with valproate . METHOD Data on age , gender , race , diagnosis , family history of diabetes , and age at clozapine initiation were collected from medical records of 82 out patients with schizophrenia or schizoaffective disorder .  Clozapine dose , data on use of valproate , and laboratory test results were recorded at 6-month intervals . RESULTS The mean age at the time of clozapine initiation of the 82 patients was 36.4 years ; 26.8 % of the patients were women , and 91.5 % were Caucasian . The mean baseline weight was 175.5 lb , and the mean body mass index was 26.9 kg/m(2 ) . Thirty patients ( 36.6 % ) were diagnosed with diabetes during the 5-year follow-up . Weight gain , use of valproate , and total daily dose of clozapine  were not significant risk factors for developing diabetes mellitus . Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine . There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level . CONCLUSIONS The results support the hypotheses that patients treated with clozapine  experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes BACKGROUND Carbamazepine is frequently used for treating bipolar disorder , but few large trials have assessed its efficacy in preventing relapse . We evaluated open-label monotherapy with beaded extended-release carbamazepine capsules ( ERC-CBZ ; SPD417 ) as continuation and short-term maintenance therapy in bipolar disorder patients with manic and mixed episodes . METHOD A 6-month , open-label study enrolled 92 patients with DSM-IV bipolar disorder ( most recent episode : 67 % [ N = 62 ] mixed , 33 % [ N = 30 ] manic ) who had participated in 2 previous 3-week , double-blind , placebo-controlled studies . Subjects received beaded ERC-CBZ ( 200 - 1600 mg/day ) , titrated at investigators ' discretion to a final mean dose of 938 mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary efficacy measure was time to relapse , and secondary efficacy measures included Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions scale ( CGI ) , and Hamilton Rating Scale for Depression ( HAM-D ) scores . Data were gathered from January 2000 to January 2002 . RESULTS Of 77 patients analyzed in the intent-to-treat population , 11 ( 14.3 % ) relapsed . Fifty-three patients ( 68.8 % ) discontinued early , including 18 ( 23.4 % ) due to adverse events . Observed mean time to relapse was 61.1 days , while estimated mean time to relapse based on the Kaplan-Meier model was 141.8 days . Improvements on the YMRS , CGI , and HAM-D from the beginning of prior double-blind treatment were maintained . The most common adverse events were headache , dizziness , and rash . No significant weight gain was noted . CONCLUSION We noted a low relapse rate with beaded ERC-CBZ in this 6-month trial . Adverse events were generally mild to moderate and were typical of those associated with carbamazepine . Controlled studies are warranted to further explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder A double-blind controlled study comparing the effects of bupropion to doxepin in out patients with primary depression was conducted to evaluate efficacy and safety differences between the two drugs . Following a 7-day placebo washout period , patients could be treated for up to 13 weeks on either treatment . Antidepressant response was assessed by the Hamilton Depression and Anxiety Scales , Clinical Global Severity and Improvement Ratings , and the Zung Self-Rating Depression Scale . Comparable efficacy between the compounds was found across the 13-week study . Doxepin differed from bupropion mainly on the sleep factor of the Hamilton Depression Scale , with doxepin improving sleep to a greater extent than bupropion . Doxepin produced a greater incidence of anticholinergic side effects , including dry mouth , constipation , sleepiness , and tiredness , in comparison to bupropion . Also , increased appetite and weight gain were consistent side effects of doxepin relative to bupropion OBJECTIVE The authors ' goal was to compare the efficacy and tolerability of 6 months ' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or 
    Output:
    