T49. THE NEURAPRO STUDY: ADHERENCE TO STUDY MEDICATION

Abstract Background Adherence to a medication is generally defined as the extent to which patients take medications as prescribed by their health care providers. Poor adherence to study medication is not uncommon posing a major challenge to treatment trails. However, poor adherence may not be randomly distributed but rather be associated with demographic or illness factors. The aim of the present study was to identify factors associated with adherence to study medication in young people at ultrahigh risk of psychosis who participated in the NEURAPRO study. Methods Secondary analysis of data collected in a multi-centre, double-blind, placebo-controlled, randomized clinical trial to prevent or delay the onset of psychosis in participants at ultrahigh risk of psychosis testing omega-3 polyunsaturated fatty acids (omega-3 PUFAs) vs. placebo, in combination with cognitive behavioural case management (NEURAPRO) were included in this analysis. Measures included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Functioning: Social and Role scales. Adherence to the study medication was assessed monthly for each participant based on capsule count. The mean adherence rating over the 6-month intervention period was then computed and categorized as either adherent (≤25% of capsules returned) or non-adherent (>25% of capsules returned). Transition to psychosis was defined on the basis of operationalized criteria and assessed with the Comprehensive Assessment of the At-Risk Mental State. Levels of ω-3 PUFAs in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (amongst other fatty acids) were measured as percentage of total fatty acids in erythrocytes at baseline and at month 6 (end-of-intervention). Results Of 304 randomised participants, 57.9% (N = 176) were non-adherent (>25% of capsules returned) and 128 (42.1%) were adherent (≤25% capsules returned) to the study medication. No sex differences were observed for adherence rates. At baseline the omega-3 index (EPA+DHA) was significantly lower in the non-adherent group (P = 0.018). The non-adherent group had significant lower scores on the SOFAS (P = 0.001) and the Global Functioning: Social and Role Scale at baseline assessment (P < 0.001 and P = 0.020, respectively) compared to the adherent group. No statistically significant differences were observed on symptom measures at baseline (BPRS, SANS, MADRS, YMRS). The cumulative transition to psychosis rate at month 12 was significantly higher in the non-adherent group compared to the adherent group (14.8% vs. 4.7%; Log rank test: P < 0.001). Discussion Adherence to study medication was relatively low in NEURAPRO. Poor functioning and lower levels of ω-3 PUFAs at baseline were associated with non-adherence. Young people who were non-adherent had a significantly higher risk of progressing to first episode psychosis. Knowledge about factors associated with adherence could help to improve the delivery of interventions in young people at risk of psychosis.

Background: Adherence to a medication is generally defined as the extent to which patients take medications as prescribed by their health care providers. Poor adherence to study medication is not uncommon posing a major challenge to treatment trails. However, poor adherence may not be randomly distributed but rather be associated with demographic or illness factors. The aim of the present study was to identify factors associated with adherence to study medication in young people at ultrahigh risk of psychosis who participated in the NEURAPRO study. Methods: Secondary analysis of data collected in a multi-centre, doubleblind, placebo-controlled, randomized clinical trial to prevent or delay the onset of psychosis in participants at ultrahigh risk of psychosis testing omega-3 polyunsaturated fatty acids (omega-3 PUFAs) vs. placebo, in combination with cognitive behavioural case management (NEURAPRO) were included in this analysis. Measures included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Functioning: Social and Role scales. Adherence to the study medication was assessed monthly for each participant based on capsule count. The mean adherence rating over the 6-month intervention period was then computed and categorized as either adherent (≤25% of capsules returned) or non-adherent (>25% of capsules returned). Transition to psychosis was defined on the basis of operationalized criteria and assessed with the Comprehensive Assessment of the At-Risk Mental State. Levels of ω-3 PUFAs in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (amongst other fatty acids) were measured as percentage of total fatty acids in erythrocytes at baseline and at month 6 (end-of-intervention). Results: Of 304 randomised participants, 57.9% (N = 176) were non-adherent (>25% of capsules returned) and 128 (42.1%) were adherent (≤25% capsules returned) to the study medication. No sex differences were observed for adherence rates. At baseline the omega-3 index (EPA+DHA) was significantly lower in the non-adherent group (P = 0.018). The non-adherent group had significant lower scores on the SOFAS (P = 0.001) and the Global Functioning: Social and Role Scale at baseline assessment (P < 0.001 and P = 0.020, respectively) compared to the adherent group. No statistically significant differences were observed on symptom measures at baseline (BPRS, SANS, MADRS, YMRS). The cumulative transition to psychosis rate at month 12 was significantly higher in the non-adherent group compared to the adherent group (14.8% vs. 4.7%; Log rank test: P < 0.001).
Discussion: Adherence to study medication was relatively low in NEURAPRO. Poor functioning and lower levels of ω-3 PUFAs at baseline were associated with non-adherence. Young people who were non-adherent had a significantly higher risk of progressing to first episode psychosis. Knowledge about factors associated with adherence could help to improve the delivery of interventions in young people at risk of psychosis. Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all at subnanomolar potency. The efficacy of brexpiprazole has been shown in both short-and long-term studies. In this post-hoc analysis from three short-term studies, the proportion of patients achieving symptomatic and functional response was assessed, grouped by age at baseline. Methods: Efficacy and functioning data were pooled from three 6-week, double-blind, placebo-controlled studies in hospitalized patients with acute exacerbation of schizophrenia (Vector [NCT01396421]; Beacon [NCT01393613]; and Lighthouse [NCT01810380]), and stratified according to age at baseline (18-35 years; and 36-65 years). For the current analyses, response was defined as reduction in PANSS score of ≥30% from baseline; a CGI-I score of 1 or 2 (much improved or improved); or reduction in PANSS score of ≥30% OR CGI-I score of 1 or 2. Functional response was defined as an increase in PSP total score of at least 10 points. The analyses were conducted using a mixed-model repeated measures (MMRM) approach with all brexpiprazole doses pooled (2-4mg/day). Results: 557 patients aged 18-35 years and 857 patients aged 36-65 years were analysed. For patients aged 18-35 years, a statistically significantly greater proportion of brexpiprazole-treated vs placebo-treated patients had symptomatic response after 6 weeks of treatment (PANSS ≥30%: 40.5% vs 28.7%, p<0.01; CGI-I 1 or 2: 39.9% vs 25.4%, p<0.001; PANSS ≥30% OR CGI-I 1 or 2: 46.2% vs 32.3%, p<0.01). Similar results were observed for patients aged 36-65 years (PANSS ≥30%: 48.7% vs 37.6%, p<0.01; CGI-I 1 or 2: 47.1% vs 32.7%, p<0.0001; PANSS ≥30% OR CGI-I 1 or 2: 54.8% vs 41.6%, p<0.001). For patients aged 18-35 years, a statistically significantly greater proportion of brexpiprazole-treated vs placebo-treated patients had functional response after 6 weeks of treatment (PSP 10 points change: 46.3% vs 33.0%, p<0.01); similar results were observed for patients aged 36-65 years (49.2% vs 38.2%, p<0.01). The proportion of patients meeting both symptomatic (using ≥30% PANSS improvement or CGI-I score of 1 or 2) and functional response was statistically significantly greater in brexpiprazole-treated patients vs placebotreated patients regardless of the age group (18-35 years: 37.4% vs 25.4%, p<0.01; 36-65 years: 41.8% vs 30.2%, p=0.01). Discussion: The results of these analyses confirm that 6 weeks of treatment with brexpiprazole results in symptomatic and functional response in acutely ill schizophrenia patients in both younger patients (age 18 to 35 years) as well as older patients (age 36-65).

T51. TREATMENT OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIA WITH TRANSCRANIAL CURRENT STIMULATION (TDCS): RESULTS OF RANDOMIZED, DOUBLE-BLINDED, SHAM-CONTROLLED TRIAL
Leandro Valiengo* ,1 , Pedro Gordon 1 , Mauricio Serpa 1 , Acioly Lacerda 2 , Wagner Gattaz 1 , Martinus Van de Bilt 1 , Helio Helkis 1 , Andre Brunoni 1 1 University of Sao Paulo; 2 Centro de Pesquisa e Ensaios Clínicos Sinapse-Bairral Background: The negative symptoms of schizophrenia cause significant distress and impairment. The treatment of them is a challenge, with medications having none or little effect. So, new treatments are necessary for this condition. The aim of the study was to ascertain the efficacy of tDCS in treating negative symptoms of schizophrenia Methods: This study was designed to be a randomized, sham-controlled, double-blinded trial using tDCS for the treatment of negative symptoms of schizophrenia. One-hundred (here we analyzed only 70% of the sample, the remaining will be presented at the meeting) patients will be enrolled and submitted to ten tDCS session over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporo-parietal junction-left (cathodal stimulation), over 5 consecutive days, with 2 mA of current. Participants were assessed with clinical and neuropsychological tests before and after the intervention. The primary outcome was change (over time and across groups) in the scores of the Negative Subscale of Positive and Negative Symptoms Syndrome (PANSS). Our secondary outcomes consist of others scales as SANSS (Scale of Assessment of Negative Symptoms), Calgary and the AHRS (Auditory Hallucinations Rating Scale). Results: From 70% of the sample the active tDCS was significantly superior to sham at endpoint at 6 weeks by negative sub scale of PANSS (mean difference, 3,5 points; SD=6.2; P<.05). The total PANSS and the hallucinations scale had no differences between both groups. The other times of analysis were not found differences between sham and active groups. The others scales (Calgary and SANSS have not being evaluated yet).

Discussion:
The results of our studies suggests a potential role of tDCS for the treatment of negative symptoms of schizophrenia. The effect size was small. This is the biggest study with tDCS for treating negative symptoms of schizophrenia until now. At the meeting all the data will be analyzed (100 patients), it these could change our preliminary results.

T52. N-ACETYL-CYSTEINE ADD-ON TREATMENT LEADS TO AN IMPROVEMENT OF FORNIX WHITE MATTER INTEGRITY IN EARLY PSYCHOSIS
Paul Klauser 1 , Lijing Xin 1 , Margot Fournier 1 , Alessandra Griffa 1 , Martine Cleusix 1 , Raoul Jenni 1 , Michel Cuenod 1 , Rolf Gruetter 1 , Patric Hagmann 1 , Philippe Conus 1 , Philipp Baumann* ,2 , Kim Q. Do 1 1 Lausanne University Hospital; 2 DP-CHUV (TIPP) Background: Beneficial effects of N-acetyl-cysteine (NAC) on negative symptoms in chronic schizophrenia have been reported in two studies. A recent study in early psychosis from our group, did not report significant improvement in negative symptoms (potentially linked to the modest baseline levels) but showed improvement in cognition (i.e. processing speed) and an increase in the brain antioxidant glutathione (GSH) levels, indicating good target engagement. 1 Indeed, research in animal models highlights the critical role of redox regulation by brain GSH for white matter maturation and maintenance. Given the strong evidence of white matter (WM) alterations in schizophrenia