Treatment For Acute Agitation And One-year Follow-up Outcomes In Patients With Schizophrenia

ObjectiveTo compare the efficacy and safety between risperidone oral solution combination clonazepam oral and haloperidol IM injection on controlling psychotic agitation in patients of acute schizophrenia and schizophrenic-affective disorder and to explore the possibility of decreasing efficacy of acute 6 weeks treatment from switching IM injection to oral.MethodIn a randomized,parallel-group,open study conducted at 6 sites in china,189 patients exhibiting agitation associated with active psychosis were randomly assigned to reveive either oral treatment with risperidone oral solution puls clonazepam(n=98) or intramuscular treatment with haloperidol (n=91).Eligible subjects will be entered 5 days treatment sessionⅠto compare the efficacy and safety between risperidone oral solution combination clonazepam oral and haloperidol IM injection on controlling psychotic agitation,then will be followed by 6 additional weeks treatment sessionⅡfor exploring the effect of medicine switching from IM injection to oral.The primary efficacy outcome measure will be the change in scores based on PANSS-EC,composed of 5 items(excitement,hostility, uncooperativeness,hallucinatory,and poor impulse control) from the Positive and Negative Syndrome Scale(PANSS) in sessionⅠ,and the response rate based on the PANSS in sessionⅡ.Safety was evaluated using Simpson-Angus Scale(ASA),Barnes Akathisia Scale(BAS),adverst events and lab test. Result(1) Mean acute-agitation score improvement were significant after 5 days treatment in both groups(p＜0.01) and were similar in both groups (p＞0.05).While the cooperation was better and the advert events,especially extrapyramidal symptoms was lower in risperdone oral solution groups than that in haloperidol group(p＜0.05).(2) Mean PANSS-EC and PANSS scores remained stable after switching from IM to oral.The efficacy was no significant difference in both groups after 6 weeks treatment(p＞0.05).There was no significant difference at the rate of total advert events(p＞0.05) while there were yet significantly higher rates of extrapyramidal symptoms in haloperidol group than that in risperidone group(p＜0.05).ConclusionThe results showed that risperidone oral solution combination clonazepam oral has similar therapeutic effect to haloperidol IM injection in the treatment of acute agitation,but risperdone oral solution has better cooperation and tolerability.Mean PANSS-EC and PANSS scores remained stable after switching from IM to oral.The efficacy were similar in both groups after 6 weeks treatment.PartⅡComparative one-year follow-up outcomes of seven antipsychotic drugs in patients with schizophreniaObjectiveTo compare the maintenance treatment effectiveness,the cognitive function effectiveness,the quality of life and social function effectiveness of seven antipsychotic agents including chlorpromazine,sulpiride,clozapine, risperidone,olanzapine,quetiapine,and aripiprazole to schizophrenia for 12 months.MethodsA total of 1227 patients suffering from schizophrenia no more than 5 years who took one of the seven study medications as maintenance treatment were recruited at 10 china sites for following up to 12 months.Study measures were administered at baseline and the end of each 3 month assessment period.The outcomes were evaluated using discontinuation of treatment and time to treatment discontinuation combined with clinical efficacy outcome.The adverse events were reported and lab tests were administered to evaluate side effects.Cognitive function was assessed at baseline and the end of each 6 month assessment period using Wisconsion card sorting test(WCST),Digit symbol test,Digit span test,Visual reproduction,Coutinuous performance test(CPT),Trail making test(TMT). SF-36 was used to evaluate quality of life of patients at baseline and the end of each 6 month assessment period.The social function of patients were assessed using GAS,which was admisitered at baseline and the end of each 3 month assessment period,ADL,admisitered at baseline and the end of each 6 month assessment period and employment rate.Results(1) Almost 44.1 percent patients discontinued their assigned treatment before 12 months.The rate of discontinuation and the time to the discontinuation of treatment for any cause had no significant difference among the seven groups.40.3 percent patients completed the one year follow-up and attained the clinical remission.At the end of 12 months,the total PANSS score was lower in olanzapine group than other groups and the difference was significant.Patients receiving risperidone,olanzapine,and aripiprazole showed greater improvement from baseline compared with patients receiving chlorpromazine and quetiapine.There was no significant difference on the total side effects while sedation,extrapyramidal symptoms, weight gain and menstrual irregularities were obvious difference among the seven antipsychotic drugs.(2) 804 patients completed the assessment of cognitive function both at baseline and the end of 6 months.After month 6,the improvement was small(-0.04～0.11).There was no significant overall difference between treatment(p＞0.05).(3) 437 patients completed the assessment of cognitive function both at baseline and the end of 12 months.After month 12,The improvement was small(-0.19～0.30).There was no significant overall difference between treatment(p＞0.05).(4) 848 patients completed the assessment of SF-36 both at baseline and the end of 12 months.After the maintain treatment of 12 month,there was no significant difference among the total score of SF-36 for senen group (p＞0.05),but there were difference among the factor scores of role-physical, vitality,role-emotional and mental health for seven group(p＜0.05).The total score of SF-36 incresed by 6.0-10.6,but there was no signinicant difference amont the variance value for seven groups(p＞0.05).However,variance value differemce among bodily pain,vitality,and mental health was significant(p＜0.05).(5) 777 patients completed the assessment of GAS and ADL both at baseline and the end of 12 months.After the maintain treatment of 12 month, the difference of GAS for seven group was signifant,the score of GAS of patients assigned olanzapine and risperidone were higher than that of other groups(p＜0.05).And there was also sifnificant difference amont the variation values compared with baseline for seven groups,which was obvious for patients assigned loanzapine,quetiapine and arisperizole (p＜0.05).There was no significant difference in the total social of ADL,the variation value compred with baseline and employment rates at the end of 12 months for seven groups(p＞0.05).Conclusions1.Clinical outcomes were similar among 7 antipsychotic drugs.The slight difference in side effects were useful guides in matching the individual sensitivities of patients to the side effect profiles of treatment.2.The cognitive function impairment of schizophrenic patients in stable stage was relative stable.The improvemt was small after 6 and 12 months treatment and there was no significant difference between seven antipsychotic drugs.3.The quality of life of schizophrenia patients can be improved and the effectivenss of seven antipsychtoc drugs were similar,while the influences for different factors were differenct.Activity of daily living of schizophrenia patients in stable phase was not obviously damaged.Social function of patientsd assigned for olanzapine and risperdone were better than other groups.Employment rates were low in each group,but there was no significant difference among seven groups.