Poster 183SEROTONIN2A RECEPTOR BLOCKADE AND CLINICAL EFFECTIN FIRST-EPISODE SCHIZOPHRENIA PATIENTS TREATEDWITH QUETIAPINE

Hans Rasmussen1, Bjorn H. Ebdrup1, David Erritzoe2,Bodil Aggernaes1, Bob Oranje1, Jan Kalbitzer2, Lars H. Pinborg2,William Baaré3, Claus Svarer2, Henrik Lublin1, Gitte M. Knudsen2,Birte Glenthoj11Psychiatric Center Glostrup Glostrup, Denmark, Denmark; 2Neurobiol-ogy Research Unit Copenhagen, Denmark, Denmark; 3Danish ResearchCenter for Magnetic Resonance Imaging Hvidovre, Denmark, Denmark

Background: We have previously reported decreased frontalcortical serotonin2A receptor binding in 30 antipsychotic naïve firstepisode schizophrenic patients and its relationship with positivesymptoms. Until now, no longitudinal studies in first-episodeantipsychotic-naïve schizophrenia patients have reported on therelationship between serotonin2A receptor occupancy and treatmenteffect after sustained treatment with one atypical antipsychoticcompound.Methods: In the current study, we measured serotonin2A receptoroccupancy with [18F]altanserin PET in 15 first-episode antipsycho-tic-naïve schizophrenia patients after 6 months of quetiapinetreatment. Moreover, we investigated possible relationships be-tween clinical efficacy, oral dose, plasma levels of quetiapine, andof the active metabolite nor-quetiapine.Results: Significant nonlinear relationships were found betweenserotonin2A receptor occupancy, quetiapine dose and plasma con-centration. The mean quetiapine dose was 383 mg corresponding to aserotonin2A receptor occupancy of 64%. There was a modest effect onpositive symptoms up until a serotonin2A receptor occupancy level ofapproximately 60%. A serotonin2A receptor occupancy level between60-70% (corresponding to 336-538 mg/day) appeared to be theoptimalwindow for treatment of positive symptoms.Occupancy levelsabove this window showed no additional treatment effect.Discussion: Summarized, the data points to a therapeutic role ofthe serotonin2A receptor in the treatment of schizophrenia. Morespecifically, the study indicates a serotonin2A receptor associatedtherapeutic window on positive symptoms in the range between60-70% occupancy in antipsychotic-naïve first-episode schizophre-nia. Future studies with concurrent measurement of multiple re-ceptor systems are warranted.

doi:10.1016/j.schres.2010.02.944

Poster 184RISPERIDONE VS PLACEBO IN THE TREATMENTOF SCHIZOPHRENIA

Ranga Rattehalli1, Mahesh Jayaram2, Michael Smith2

1NHS North Yorkshire and York York, North Yorkshire, United Kingdom;2Leeds PFT Leeds, West Yorkshire, United Kingdom

Background: Risperidone is the first new generation antipsychoticdrug made available in the market in its generic form. It has beenused in the treatment of schizophrenia and related psychoticdisorders for over a decade. We examined the clinical effects of oralrisperidone for people with schizophrenia and schizophrenia-likepsychoses in comparison with placebo.Methods: We searched the Cochrane Schizophrenia Group'sRegister (February 2008), references of all included studies, andcontacted industry and authors of included studies for relevantstudies and data. All randomised clinical trials comparing oral

risperidonewith placebo treatments for people with schizophreniaand/or schizophrenia-like psychoses were collected. Two re-viewers independently inspected citations and/or abstracts, or-dered papers, re-inspected and assessed the quality of results andextracted data. For dichotomous data, we calculated the relativerisk (RR), the 95% confidence interval (CI) and, where appropriate,the number needed to treat (NNT), on an intention-to-treat basis.For continuous data, we calculated weighted mean differences(WMD).Results: All ten included studies were described as double blind,but none of them tested for the effectiveness of blinding for eitherparticipants or raters. One study (n=599) compared risperidoneagainst placebo but the attrition rate was 60% over a period of sixweeks rendering most of the efficacy and global improvement dataunusable. The attrition rate was higher for placebo compared withrisperidone (n=1363, 10 RCTs, RR 0.70 CI 0.57 to 0.86, NNT 13 CI 9to 29) and less participants left the trial in the risperidone arm dueto lack of efficacy (n=888, 5 RCTs, RR 0.38 CI 0.20 to 0.73, NNT 7 CI5 to 15). Risperidone was no better than placebo on the CGI globalscore (n=397, 3 RCTs, RR 0.80 CI 0.55 to 1.15) but significantlymore number of participants in risperidone arm had more than 20%reduction in their BPRS/PANSS score (n=856, 7 RCTs, RR 0.43 CI 0.32to 0.58, NNT 7 CI 6 to 10). Data became considerably morehomogeneous (and positive) when the one study independent ofindustry funding was removed (I2 75% to 55%). Despite poorreporting, it is clear that around 24% of all participants receivingeither risperidone or placebo developed some form of extrapyramidaleffects (n=723, 5 RCTs, RR 1.40 CI 0.93 to 2.10). Three people onrisperidone had prolonged QTc (n=198, 1 RCT, RR 7.5 CI 0.4 to 144),more on risperidone gained weight (n=303, 2 RCTs, RR 5.14 CI 1.79to 14.73, NNH 10 CI 3 to 51) and had a raised prolactin (n=323, 2RCTs, RR 12.54 CI 5.11 to 30.79, NNH 3 CI 2 to 5). Fewer in therisperidone arm needed an additional psychotropic during the trialperiod (n=186, 1 RCT, RR 0.62 CI 0.45 to 0.85, NNT 10 CI 7 to 28).Discussion: Risperidone appears to have a marginal benefit interms of clinical improvement compared with placebo in the firstfew weeks of treatment but data are limited, poorly reported andprobably biased in favour of risperidone. The margin of improve-ment chosen by the researchers as their outcome may not beclinically meaningful. Even after so much use of this drug, we feelthat further independent trials can be justified.

doi:10.1016/j.schres.2010.02.945

Poster 185A FIVE YEAR FOLLOW-UP STUDY: OUTCOME OFSCHIZOPHRENIC PATIENTS

Teresa Bel, Isabel Frigola, Vincente Fabregat, Carlos Conesa, RaquelBorrego, Antoni CorominasMental Health Service, Fundacio Privada Hospital de Mollet Del Valles,Barcelona, Spain

Background: There is consensus in literature on the variability ofschizophrenia prognosis. It is assumed that neither specific ambientfactors nor prodromic symptoms nor signs at the onset of the illnesshave any strong correlation with long term prognosis. Nevertheless,from a literature review, we can extract some indicators of prognosis,some of which are the natural development of illness, previous socialadjustment and clinical symptoms through the courseof the illness. Tostudy which variables affect clinical course in an outpatient clinicalschizophrenic sample. Patients were evaluated at baseline andprospectively on three more cut-off points during a 5 year follow-upperiod using PANSS subscale scores and its correlationwith the age ofonset, gender and intelligence quotient (IQ).

Abstracts 497