PREDICTORS FOR HIGH TREATMENT RESPONSE IN ACUTE PATIENTS WITH SCHIZOPHRENIA

Abstracts 1 Janssen Cilag GmbH EMEA Medical Affairs Neuss Germany; 2Ankara Numune Training and Research Hospital Ankara Turkey; 3Beer YaakovNess Ziona Mental Health Center Beer Yaakov Israel; 4Casa de Saude de S. Rafael Angra do Heroismo Portugal; 5Janssen Pharmaceutica N. V. Beerse Belgium; 6Dromokaiteion Psychiatric Hospital of Attica Athens Greece; 7University Hospital Alexandrovska Sofia Bulgaria; 8Janssen Cilag France Issy-Les-Moulineaux France; 9Mental Health Research Center Mowcow Russia

Background: To explore tolerability, safety and treatment response with flexibly dosed paliperidone ER in non-acute adult patients with schizophrenia previously unsuccessfully treated with oral olanzapine. Methods: Prospective 6-month open-label study. Assessments included the Positive and Negative Syndrome Scale (PANSS), patient functioning (Personal and Social Performance Scale (PSP)), patient satisfaction, extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale; ESRS), adverse events (AEs) and weight change. Results: 395 patients were analyzed (65.3% male, mean age [±SD] 40.1 ± 12.0 years,); most were enrolled because of lack of efficacy (n= 210) or lack of tolerability (n= 140) with prior olanzapine treatment. 65.6% of subjects completed the 6-month study. Most frequent reasons for early discontinuation were subject choice (11.1%), AE (5.8%), or lack of efficacy combined with an AE (5.6%). The median mode dose of paliperidone ER was 6 mg/day. Mean PANSS total score decreased from 78.1 ±21.4 at baseline to 67.9± 21.4 at endpoint (mean change -10.2 ± 20.7; 95% confidence interval -12.3;-8.1, p < 0.0001). The percentage of patients rated mildly ill or less in CGIS increased from 26.3% to 45.8%. Mean PSP scores improved by 5.0 ± 15.2 to 63.7± 15.3 (p< 0.001). Total ESRS decreased significantly from 2.8 ± 5.0 to 2.0 ± 4.3 (p< 0.0001). AEs reported in>=5% of patients were insomnia (15.2%), anxiety (7.8%) and somnolence (5.1%). Mean body weight decrease at endpoint was -0.8± 5.2 kg (p= 0.005). At endpoint, 65.3% of patients rated treatment satisfaction with paliperidone ER as "good" or "very good". Discussion: These data support results from recent studies that flexibly dosed paliperidone ER in non-acute patients with schizophrenia is safe, well tolerated and efficacious, including patients previously unsuccessfully treated with oral olanzapine. doi:10.1016/j.schres.2010.02.949

Poster 189 A FLEXIBLE-DOSE STUDY OF PALIPERIDONE ER IN NON-ACUTE PATIENTS WITH SCHIZOPHRENIA PREVIOUSLY UNSUCCESSFULLY TREATED WITH ARIPIPRAZOLE Andreas Schreiner1, Dagmar Hoeben2, Marjolein Lahaye3, Christophe Tessier4, Dieter Naber5, Jozef Peuskens6, Roland Vauth7, Miroslava Jasovic Gasic8, Elmars Rancans9, Roy Didi10 1 Janssen Cilag GmbH EMEA Medical Affairs Neuss Germany; 2Janssen Pharmaceutica N.V. Beerse Belgium; 3Janssen Cilag Netherlands Tilburg Netherlands; 4Janssen Cilag France Issy-Les-Moulineaux France; 5Universitätsklinikum Hamburg-Eppendorf Hamburg Germany; 6University Psychiatric Centre St.-Jozef Kortenberg Belgium; 7Psychiatric Outpatient Dept. University of Basel Basel Switzerland; 8Universtiy of Belgarde, Institute for Psychiatry Belgrade Serbia; 9Riga Stradins University Riga Latvia; 10CHS de la Chartreuse Dijon France Background: To explore tolerability, safety and treatment response of flexible doses of paliperidone ER in adult non-acute patients with schizophrenia previously unsuccessfully treated with aripiprazole. Methods: Prospective international 6-month open-label study. Assessments were the Positive and Negative Syndrome Scale

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(PANSS), Clinical Global Impression-Severity Scale (CGI-S), Personal and Social Performance Scale (PSP), adverse events (AEs), extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale; ESRS), and weight change. Results: 140 patients were included (55.7% male, mean age [±SD] 37.8±10.9 years); most were enrolled because of lack of efficacy (n = 93) or lack of tolerability (n = 31) with prior aripiprazole treatment. 67.1% (n = 94) completed the 6-month study. Most frequent reasons for early discontinuation were patient choice (10.0%), AE (6.4%) and AE combined with lack of efficacy (5.0%). The median mode dose of paliperidone ER was 6 mg/day, independent of reason for switching. Across all patients, mean PANSS total score decreased significantly from 80.4± 20.7 at baseline to 68.9± 19.1 at endpoint (mean change -11.5 ± 17.7; 95% confidence interval -14.5;-8.5, p < 0.0001). Percentage of patients rated mildly ill or less (CGI-S) increased from 19.7% to 44.6% at endpoint, and the rate of patients with mild functional impairment as measured by PSP increased from 19.5% to 28.1%. ESRS decreased significantly from 3.2 ±4.4 to 2.3± 4.3 (p= 0.0007). AEs reported in>= 5% of patients were insomnia (7.9%), anxiety (7.9%), somnolence (7.1%), weight increased (6.4%) and akathisia (5.0%). Mean weight change from baseline to endpoint was 0.5± 4.7 kg. Discussion: These data support results from recent randomized controlled studies that paliperidone ER is safe, well tolerated and effective, including patients previously unsuccessfully treated with aripiprazole. doi:10.1016/j.schres.2010.02.950

Poster 190 PREDICTORS FOR HIGH TREATMENT RESPONSE IN ACUTE PATIENTS WITH SCHIZOPHRENIA Andreas Schreiner1, Dagmar Hoeben2, Christophe Tessier3, Liana Don4, Stephan Heres5, Valentinas Maciulis6, Zeev Kaplan7, Miroslav Herceg8, Leszek Bidzan9, Michel Blanc10, Alberto Siracusano11 1 Janssen Cilag EMEA Medical Affairs Neuss Germany; 2Janssen Pharmaceutica N. V. Beerse Belgium; 3Janssen Cilag France Issy-LesMoulineaux France; 4County Hospital, Psychiatry Clinic no. 1 ClujNapoca Rumania; 5Klinik und Poliklinik for Psychiatry and Psychotherapy Munich Germany; 6Republican Vilnius Psychiatric Hospital Vilnius Lithuania; 7Beer-Sheva Mental Health Center Negev Israel; 8Psychiatric Hospital Vrapce Zagreb Croatia; 9Medical University of Gdansk Gdansk Poland; 10Centre Hospitalier Jury les Metz - 5ème Secteur Metz France; 11 Universitaria Policlinico Tor Vergata, Dept. of Psychiatry Roma Italy Background: To explore predictors for treatment response in patients with schizophrenia suffering from an acute episode treated with flexible doses oral paliperidone ER. Methods: Six-week prospective international, open-label flexible dose study in acutely exacerbated patients with schizophrenia. Treatment response was defined as >=30% improvement in total PANSS and >=1 point in CGI-S. Super-responders were defined as >=50% improvement in total PANSS and >=2 points in CGI-S. Early response was defined as achievement of criteria mentioned above within the first 2 weeks of treatment. For predictor analysis, a stepwise logistic regression model was used. Results: 294 patients were analyzed (53% male, mean age 40.3± 12.4 years, mean average daily paliperidone ER dose 7.5±2.1 mg). 80% of patients completed the study. Mean total PANSS score improved from 100.2±17.2 at baseline to 72.7±20.3 at endpoint (p<0.0001), and a significant onset of efficacy was observed as of day 2 of treatment. Treatment response was predicted by type of schizophrenia (in par-

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ticular paranoid versus residual; p<0.01), early response and differences between participating countries (p<0.001), and there was a trend for patients hospitalized in the last 12 months (p= 0.0785). Superresponders were predicted by female gender (p<0.01), high CGI-S baseline score and early response (p<0.001). Age, body mass index and total PANSS score at baseline did not predict treatment response. Discussion: In patients with schizophrenia suffering from an acute episode, treatment response was predicted by different demographic and clinical factors. As recently described in the literature, early response was a consistent predictor for high treatment response at endpoint. doi:10.1016/j.schres.2010.02.951

Poster 191 ADJUNCTIVE VARENICLINE TREATMENT WITH ANTIPSYCHOTIC MEDICATIONS IN PATIENT WITH SCHIZOPHRENIA: A PLACEBO-CONTROLLED TRIAL Joo-Cheol Shim1, Do-Un Jung2, Sung-Soo Jung3, Young-Soo Seo3, Bo-Geum Kong1, Min-Kyung Oh1, Robert P. McMahon4, Deanna L. Kelly4 1 Inje University Busan, Busan, Korea; 2Dongrae Hospital Busan, Busan, Korea; 3Nanumhaengbok Hospital Busan, Busan, Korea; 4University of Maryland Balitimore, Maryland, USA Background: Several evidences have supported the fact that nicotine through the nicotinic acetylcholine receptor system may be effective in improving cognitive dysfunction that is a core symptom domain of schizophrenia. The objective of this project was to examine the effects of varenicline treatment, a partial agonist at the α4β2 nicotine acetylcholine receptor, and a full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. Methods: This study was a randomized, double blind, parallel group, placebo controlled 8 week trial. 120 people with schizophrenia (60 smokers and 60 nonsmokers) participated in this trial. The dose of antipsychotic and concomitant medications remained fixed throughout the study and the titration of varenicline was as follows: varenicline 0.5 mg/d for days 1 to 3, 0.5 mg twice per day for days 4 to 7, then 1 mg twice daily through week 8. Neuropsychological assessment was performed at baseline, at baseline, week 1, 2, 4, and 8 by using Continuous Performance Test(CPT), Stroop Color Word Test, Wisconsin Card Sorting Test(WCST), Digital Symbol Substitution Test. A neuropsychological test battery was administered at baseline, at baseline, week 1, 2, 4, and 8. Safety assessments related to medication adverse events included the Simpson-Angus Rating Scale (SARS), the Barnes Akathisia Rating Scale (BARS), and a Side Effect Checklist. The Student's T-test, Wilcoxon Rank Sum test, Kruscal Wallis test, Pearson's Chi-square test, Fisher's exact test, and mixed model ANCOVA were used for data analysis. Results: No significant difference was found in age, sex ratio, duration of illness, CPZ equivalent dose of antipsychotic drug and severity of psychopathology measuring by PANSS, SANS, HDRS between varenicline and placebo group. 91 patients completed the study (45 varenicline and 46 placebo) and 29 patients were dropout from the study. There were significant time main effects for WCST categories completed (p =0.034) ;WCST total error (p=0.012); Stroop Test incongruent error (p=0.0046). No significant time x treatment or time x treatment x smoking effects was found. For the varenicline main effects, the average difference between varenicline and placebo was found for CPT omission (p=0.004); CPT hit reaction time (p =0.07), DSST (p =0.013) and WCST non-perseverative errors (p =0.043). For the smoking main effect, there are a number of significant main effects

of smoking not the smoking by treatment interaction, suggesting that there are differences in level of performance between smokers and nonsmokers that are not altered by varenicline. These variables included CPT omission (p =0.012); DSST (p =0.026); visual span (p=0.0006); Stroop incongruent errors (p =0.03). For the smoking x treatment suggesting varenicline alters the differences between smokers and nonsmokers, Significant (p< 0.05) or trend (p <0.10) smoking x treatment interactions included: CPT hit reaction time (p=0.04) and detectability (p=0.06); Digit span backward (p=0.03); Stroop incongruent RT (p=0.009); WCST categories (p=0.07). No significant changes were found in total scores of SARS, BARS over time and no serious adverse event was not reported after adding varenicline. Discussion: Overall, we did not support beneficial effect of varenicline augmentation on cognitive symptom in main analysis, though explorative analyses suggest that there might be limited cognitive effects in some domains of neuropsychological assessment. Varenicline improved cognitive dysfunction more in smokers than non-smokers. doi:10.1016/j.schres.2010.02.952

Poster 192 METABOLIC PARAMETERS IN A SUBSET OF PATIENTS IN THE SCOP STUDY Marc De Hert1, Aurélia Mittoux2, Yuan He2, Joseph Peuskens1 1 University Psychiatric Center Catholic University Leuven Kortenberg Belgium; 2H. Lundbeck A/S Copenhagen Denmark Background: People with severe mental illness have nearly twice the normal risk of dying from cardiovascular disease (Fleischhacker et al., 2008; Laursen et al., 2009; Weinmann et al., 2009). There is a growing concern about the risk of cardiovascular disease in people with schizophrenia (Casey et al., 2004; De Hert et al., 2009) The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. The sertindole cohort prospective (SCoP) study was carried out to confirm the short and long term safety of sertindole. The objective of the metabolic substudy was to evaluate the effect of short and long-term treatment with sertindole or risperidone on metabolic variables in patients with schizophrenia in a subset of patients enrolled in the SCoP study. Methods: Randomized study of the short- and long-term metabolic safety of sertindole compared to that of risperidone in a subset of patients enrolled in the sertindole cohort prospective (SCoP) study. Metabolic assessments were carried out at Weeks 8 and 12 and every 3 months thereafter. The following parameters were measured: weight, waist circumference, blood pressure, fasting plasma glucose and fasting serum lipids. The International Diabetes Federation (IDF) definition of MetS was used. Results: The mean treatment exposure was approximately 7 months in the risperidone group and 6 months in the sertindole group. In 261 randomized patients, there were moderate increases in mean weight, BMI, and waist circumference during treatment with either sertindole or risperidone; after 12 weeks, the increase in weight was 1.3 kg and 1.1 kg, respectively, and after 36 weeks it was 2.2 kg and 2.0 kg, respectively. From baseline to last assessment (up to 60 weeks) weight gains of 1.8 kg and 1.7 kg for sertindole and risperidone, respectively were observed. Similar proportions of patients (sertindole: 17% versus risperidone: 16%) had weight increases ≥7% from baseline to last assessment. The mean changes from baseline in triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small and not clinically relevant in both treatment groups. No patient in either of the groups developed type 2 diabetes during the study. At baseline, the prevalence of MetS was lower in the sertindole group (13%) than in the risperidone group