- Email: [email protected]
P.3.a.012 Impact of improving negative symptoms on functioning in patients with schizophrenia: a post-hoc analysis of a proof-of-concept study
S310
P.3.a. Psychotic disorders and antipsychotics − Psychotic disorders (clinical)
continuous variables (e.g. calorie intake), that were considered the dependent variable. Antipsychotic treatment was included as four independent variables: 1) risperidone or paliperidone, 2) olanzapine, 3) aripiprazole or 4) other antipsychotic drugs. Standardized betas are reported. A p value <0.05 (bilateral) was considered to be significant. Results: The mean (standard deviation) percentages of macronutrient intake of the sample were: 37.2% (7.9) lipids, 16.6% (3.8) protein, 44.9% (9.6) carbohydrates. The intake of saturated fat was 12.8% (4.3), and refined sugars 19.9% (8.2). Calorie intake per kilogram was 33.7 (10.8). In relation to overeating episodes, 64.2% of the sample reported grazing or binging. There were no significant differences between diagnostic groups (first episode, critical period, high-risk). We explored the relationship between antipsychotic treatment and dietary habits in those subjects with a psychotic period (N = 58). We found a significant positive association between olanzapine treatment and calorie intake per kg (B = 0.289, p = 0.045). No differences were found among antipsychotic drugs and intake of macronutrients or saturated fat. Aripiprazole was negatively associated with consumption of refined sugar (B = −0.349, p = 0.023). Conclusions: Subjects with early psychosis show an increased calorie intake with excessive consumption of saturated fat and refined sugar, without differences among diagnostic groups. Of all antipsychotic drugs, olanzapine was associated with an increased calorie intake.
in patients who completed 8 weeks of treatment in a phase 2 proofof-concept (POC) study. The objective of this post-hoc analysis of the POC study data was to examine the correlation between negative symptom reduction and functional improvement. Methods: Clinically stable patients with predominant negative symptoms were randomized to receive bitopertin (10 mg, 30 mg, or 60 mg) or placebo once daily for 8 weeks in combination with second generation antipsychotics, and their responses were monitored. Patients were categorized as being responsive or unresponsive to treatment based on the degree of improvement in their negative symptoms. The following responder definitions were used: (1) a 20% improvement on the Positive and Negative Syndrome Scale (PANSS) negative symptom factor score (NSFS); (2) a Clinical Global Impression − Improvement in Negative Symptoms (CGI-I-N) score of 1 or 2 (very much or much improved, respectively); and (3) a combination of both definitions. The clinical relevance of negative symptom reduction for patient functioning was assessed by correlating negative symptom changes with changes in the Personal and Social Performance (PSP) scale scores in the per protocol (PP) population (patients who completed 8 weeks of treatment). Results: 323 patients were randomized with the following baseline characteristics: [mean±SD] age = 39.9±10.1 years; PANSS total = 79.2±9.3; PANSS NSFS = 26.1±3.9; 321 patients comprised the intent-to-treat population and the PP population included 231 patients. Changes in PSP scores for responding patients are summarized in Table 1.
References
Table 1. Changes in PSP score for responders (PP population)
[1] Foley D., Morley K., 2011 Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry, 68(6): 609–616. [2] Ryan M., Collins P., 2003 Impaired fasting glucose tolerance in firstepisode, drug-na¨ıve patients with schizophrenia. American Journal of Psychiatry, 160, 284–289. [3] Stokes C., Peet M., 2003 Dietary sugar intake and the severity of symptoms of schizophrenia. MSC Thesis. Sheffield: University of Sheffield.
Response definition
Disclosure statement: This work was supported by grants from Fundaci´o La Marat´o de TV3 (092230/0922431) and from Instituto de Salud Carlos III (FIS, PI10/01607). Javier Labad has received an Intensification of Research Activity grant (Programme I3SNS-INT 11/323) from the Instituto de Salud Carlos III (Spain) during 2012.
P.3.a.012 Impact of improving negative symptoms on functioning in patients with schizophrenia: a post-hoc analysis of a proof-of-concept study T. Bl¨attler1 ° , C. Edgar2 , G. Garibaldi3 1 F. Hoffmann-La Roche Ltd., PDND Clinical Development − CNS, Basel, Switzerland; 2 Roche Products Limited, Roche Products Limited, Welwyn, United Kingdom; 3 F. Hoffmann-La Roche Ltd., CNS Clinical Development, Basel, Switzerland Background: Cognitive deficits and negative symptoms are the main determinants of long-term disability in patients with schizophrenia. In particular, negative symptoms impair social functioning [1]. Both negative and positive symptoms of schizophrenia have been attributed to hypofunction of the N-methyl-D-aspartate (NMDA) receptor. NMDA receptor function can be enhanced safely by increasing availability of the obligatory co-agonist, glycine. Bitopertin (RG1678), a potent and selective glycine reuptake inhibitor (GRI), reduced negative symptoms of schizophrenia
Responding Mean change in PSP score patients of responding patients
CGI-I-N score of 1 (very much improved) 32.5% or 2 (much improved) 20% Improvement in PANSS NSFS 52.8% Combined response (CGI-I-N score of 1 30.7% or 2 and a 20% improvement in PANSS NSFS)
14 12 14
Patients who did not meet response criteria based on any definition achieved corresponding mean changes in PSP score ranging between 3 and 4. Discussion: In a POC study of patients with schizophrenia manifesting predominant negative symptoms while receiving second generation antipsychotics, responders, as defined by degree of improvement in negative symptoms, demonstrated greater improvement in function based on the PSP scale score. A change of 7 points on the PSP scale has been established as clinically meaningful in stable schizophrenic patients, corresponding to one category improvement or worsening on the CGI-severity scale [2]. In the current analysis, responding patients achieved an improvement in functioning that was approximately double this predefined threshold. These findings suggest that an improvement in negative symptoms is associated with a clinically meaningful improvement in functioning. References [1] Hunter, R., Barry, S., 2011 Negative symptoms and psychosocial functioning in schizophrenia: Neglected but important targets for treatment. Eur Psychiatry. [2] Nasrallah, H., Morosini, P., Gagnon, D.D., 2008 Reliability, validity and ability to detect change of the Personal and Social Performance scale in patients with stable schizophrenia. Psychiatry Res. 16: 213. Disclosure statement: Thomas Bl¨attler, Christopher Edgar and George Garibaldi are employees of F. Hoffmann-La Roche LTD.
P.3.a. Psychotic disorders and antipsychotics − Psychotic disorders (clinical)
continuous variables (e.g. calorie intake), that were considered the dependent variable. Antipsychotic treatment was included as four independent variables: 1) risperidone or paliperidone, 2) olanzapine, 3) aripiprazole or 4) other antipsychotic drugs. Standardized betas are reported. A p value <0.05 (bilateral) was considered to be significant. Results: The mean (standard deviation) percentages of macronutrient intake of the sample were: 37.2% (7.9) lipids, 16.6% (3.8) protein, 44.9% (9.6) carbohydrates. The intake of saturated fat was 12.8% (4.3), and refined sugars 19.9% (8.2). Calorie intake per kilogram was 33.7 (10.8). In relation to overeating episodes, 64.2% of the sample reported grazing or binging. There were no significant differences between diagnostic groups (first episode, critical period, high-risk). We explored the relationship between antipsychotic treatment and dietary habits in those subjects with a psychotic period (N = 58). We found a significant positive association between olanzapine treatment and calorie intake per kg (B = 0.289, p = 0.045). No differences were found among antipsychotic drugs and intake of macronutrients or saturated fat. Aripiprazole was negatively associated with consumption of refined sugar (B = −0.349, p = 0.023). Conclusions: Subjects with early psychosis show an increased calorie intake with excessive consumption of saturated fat and refined sugar, without differences among diagnostic groups. Of all antipsychotic drugs, olanzapine was associated with an increased calorie intake.
in patients who completed 8 weeks of treatment in a phase 2 proofof-concept (POC) study. The objective of this post-hoc analysis of the POC study data was to examine the correlation between negative symptom reduction and functional improvement. Methods: Clinically stable patients with predominant negative symptoms were randomized to receive bitopertin (10 mg, 30 mg, or 60 mg) or placebo once daily for 8 weeks in combination with second generation antipsychotics, and their responses were monitored. Patients were categorized as being responsive or unresponsive to treatment based on the degree of improvement in their negative symptoms. The following responder definitions were used: (1) a 20% improvement on the Positive and Negative Syndrome Scale (PANSS) negative symptom factor score (NSFS); (2) a Clinical Global Impression − Improvement in Negative Symptoms (CGI-I-N) score of 1 or 2 (very much or much improved, respectively); and (3) a combination of both definitions. The clinical relevance of negative symptom reduction for patient functioning was assessed by correlating negative symptom changes with changes in the Personal and Social Performance (PSP) scale scores in the per protocol (PP) population (patients who completed 8 weeks of treatment). Results: 323 patients were randomized with the following baseline characteristics: [mean±SD] age = 39.9±10.1 years; PANSS total = 79.2±9.3; PANSS NSFS = 26.1±3.9; 321 patients comprised the intent-to-treat population and the PP population included 231 patients. Changes in PSP scores for responding patients are summarized in Table 1.
References
Table 1. Changes in PSP score for responders (PP population)
[1] Foley D., Morley K., 2011 Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry, 68(6): 609–616. [2] Ryan M., Collins P., 2003 Impaired fasting glucose tolerance in firstepisode, drug-na¨ıve patients with schizophrenia. American Journal of Psychiatry, 160, 284–289. [3] Stokes C., Peet M., 2003 Dietary sugar intake and the severity of symptoms of schizophrenia. MSC Thesis. Sheffield: University of Sheffield.
Response definition
Disclosure statement: This work was supported by grants from Fundaci´o La Marat´o de TV3 (092230/0922431) and from Instituto de Salud Carlos III (FIS, PI10/01607). Javier Labad has received an Intensification of Research Activity grant (Programme I3SNS-INT 11/323) from the Instituto de Salud Carlos III (Spain) during 2012.
P.3.a.012 Impact of improving negative symptoms on functioning in patients with schizophrenia: a post-hoc analysis of a proof-of-concept study T. Bl¨attler1 ° , C. Edgar2 , G. Garibaldi3 1 F. Hoffmann-La Roche Ltd., PDND Clinical Development − CNS, Basel, Switzerland; 2 Roche Products Limited, Roche Products Limited, Welwyn, United Kingdom; 3 F. Hoffmann-La Roche Ltd., CNS Clinical Development, Basel, Switzerland Background: Cognitive deficits and negative symptoms are the main determinants of long-term disability in patients with schizophrenia. In particular, negative symptoms impair social functioning [1]. Both negative and positive symptoms of schizophrenia have been attributed to hypofunction of the N-methyl-D-aspartate (NMDA) receptor. NMDA receptor function can be enhanced safely by increasing availability of the obligatory co-agonist, glycine. Bitopertin (RG1678), a potent and selective glycine reuptake inhibitor (GRI), reduced negative symptoms of schizophrenia
Responding Mean change in PSP score patients of responding patients
CGI-I-N score of 1 (very much improved) 32.5% or 2 (much improved) 20% Improvement in PANSS NSFS 52.8% Combined response (CGI-I-N score of 1 30.7% or 2 and a 20% improvement in PANSS NSFS)
14 12 14
Patients who did not meet response criteria based on any definition achieved corresponding mean changes in PSP score ranging between 3 and 4. Discussion: In a POC study of patients with schizophrenia manifesting predominant negative symptoms while receiving second generation antipsychotics, responders, as defined by degree of improvement in negative symptoms, demonstrated greater improvement in function based on the PSP scale score. A change of 7 points on the PSP scale has been established as clinically meaningful in stable schizophrenic patients, corresponding to one category improvement or worsening on the CGI-severity scale [2]. In the current analysis, responding patients achieved an improvement in functioning that was approximately double this predefined threshold. These findings suggest that an improvement in negative symptoms is associated with a clinically meaningful improvement in functioning. References [1] Hunter, R., Barry, S., 2011 Negative symptoms and psychosocial functioning in schizophrenia: Neglected but important targets for treatment. Eur Psychiatry. [2] Nasrallah, H., Morosini, P., Gagnon, D.D., 2008 Reliability, validity and ability to detect change of the Personal and Social Performance scale in patients with stable schizophrenia. Psychiatry Res. 16: 213. Disclosure statement: Thomas Bl¨attler, Christopher Edgar and George Garibaldi are employees of F. Hoffmann-La Roche LTD.