Clozapine versus typical neuroleptic medication for schizophrenia.

Summary of findings for the main comparison CLOZAPINE versus TYPICAL ANTIPSYCHOTICS -OVERALL for schizophrenia; Summary of findings 2 CLOZAPINEversusTYPICALANTIPSYCHOTICS forpeoplewithschizophreniawhose illnesshasprovedresistant totreatment1. COMPARISON 1. CLOZAPINE versus TYPICAL AN-TIPSYCHOTIC DRUGS - OVERALLAll data are derived from 50 studies.1.1 DeathFour deathsoccurredin614peopletreatedwithtypicalneurolep-tics compared with three deaths in 629 people treatedwith cloza-pine. There were no significant differences in mortality betweengroups (n=1243, 12 RCTs, RR 0.56 CI 0.1 to 2.3).1.2 Relapse rateWe included 19 short-term studies, and found incidences of re-lapse werelowerin theclozapine group (n=1303, RR 0.62 CI0.5to0.8,NNT21CI15to49)comparedwithtypicalantipsychoticdrugs. Long-term data (4 RCTs, n=578) also favoured clozapinebut data were heterogeneous (I-squared =76%) (RR 0.22 CI 0.1to 0.3).1.3 Global impression1.3.1 Clinical improvement as defined by study authorsWefound thatthenumber ofparticipants whohadnot improvedwere lower in the clozapine group (n=1119, 14 RCTs, RR 0.72CI 0.7 to 0.8, NNT 6 CI 5 to 8). Three long-term studies alsofavoured clozapine (n=719, RR 0.81 CI 0.7 to 0.9) but the dataare heterogeneous (I-squared statistic 81%).1.3.2 Readiness for hospital dischargeThere were no significant differences between treatment groupsfor the number of participants who were judged to be not readyfordischarge(short-term,n=447,5RCTs,RR0.88CI0.8to1.0).Long-termdataalsofailedtoshowasignificant difference(n=648,2 RCTs, RR 0.82 CI 0.6 to 1.1).1.4 Hospitalisation - Not discharged or readmitted within oneyear after dischargeData were available from two long-term studies (Essock 1996(H/CPZ/Flu),Rosenheck1993(H)),andwefoundnosignificantadvantageforclozapine(n=648,RR0.94CI0.9to1.0)comparedwith typical antipsychotic drugs.1.5 Unable to workWe found no significant difference in the number of participantswho were assessed as being unable to work (n=416, 4 RCTs, RR0.87CI0.8to1.0),althoughthedatasuggestedatrendfavouringclozapine (p=0.06).1.6 Participant dissatisfactionNosignificantdifferenceswerefoundfordissatisfactionwithtreat-mentintwoshort-termstudies(n=114,RR0.72CI0.4to1.3).Wefoundlonger-termdatain(Rosenheck1993(H)).Thesefavouredtheclozapinegroupwhowerelessdissatisfiedwiththeirtreatmentcomparedwithconventionalantipsychoticdrugs(n=423,RR0.45CI 0.3 to 0.8, NNT 13 CI 9 to 37).1.7 Leaving the study early - acceptability of treatmentWe used leaving the study early data as a proxy measure for theacceptability of treatment. Short-term data from 32 studies in-volving 2316 participants indicated that significantly more par-ticipantsgivenclozapinefoundtreatmentacceptable(RR0.81CI0.7 to 1.0, NNT 35 CI 20 to 217). Longer-term data from sixstudies showed a significant benefit in the clozapine group (n=982,RR0.60CI0.5to0.7,NNT15CI12to20).Thelong-termattrition rate fromclozapine treatment isapproximately 33% and56% when treated with typical antipsychotic drugs.1.8 Mental state1.8.1 BPRS and PANSSWe found BPRS mental state scores favoured clozapine duringshort-termassessmentin16studies(n=1205,WMD-3.79CI-4.9to -2.7), although the data were heterogeneous (I squared=69%).Longer-term BPRS data (Lee 1994 (mainly H)) were equivocal(n=52, WMD 0.80 CI -5.7 to 7.3). PANSS scores from threeChinesetrialsfavouredtheclozapinegroups(n=163,WMD-3.82CI -7.4 to -0.3) during short-term analysis. Also, PANSS scoresassessed over the long-term favoured clozapine (Rosenheck 1993(H), n=235, WMD -6.90 CI -10.7 to -3.1).1.8.2 Negative symptomsShort-termcontinuous data on negative symptom scores from sixshort-termtrialswith236participantsfavouredclozapine(SANS,WMD -7.12 CI -8.8 to -5.5) but these are heterogeneous data(Isquared=92%). Longer-termnegativesymptomsscoresassessedwiththePANSSnegativesubscorewerenotsignificantlydifferent(Rosenheck 1993 (H), n=235, WMD -0.90 CI -6.6 to 4.8).1.8.3 Positive symptomsWe found short-term SAPS scores were equivocal (Wang 2001(CPZ), n=60, WMD 4.39 CI -12.2 to 20.9). Longer-term datafrom the PANSS positive scores favoured clozapine (Rosenheck1993 (H), n=235, WMD -2.20 CI -3.3 to -1.1).1.9 Cognitive functionCognitive impairment from one small study (n=82) favoured theclozapine group who experienced less impairment (Klieser 1990(H),RR0.56CI0.3to0.9,NNT4CI3to21)whenassessedwiththe SKT scale compared with those given typical antipsychoticdrugs.Onesmallstudy(Lee1994(mainlyH),n=54)reporteddataon aseriesof cognitive functioning tests(verbal,memory or exec-utive functions etc.) and we found outcomes to be equivocal, ex-cept for ’psychomotor speedand attention’ scoreswhich favouredthe clozapine-treated participants over the three pre-stated cut-off points (short-term, WMD 1.40 CI 0.2 to 2.6, medium-term,WMD1.30CI0.01to3.0,long-term,WMD2.10CI0.8to3.4).Clozapine versus typical neuroleptic medication for schizophrenia (Review)