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Poster #215 PREHYPERTENSION, HYPERTENSION, DIABETES, OBESITY AND CARDIOMETABOLIC CHANGES ASSOCIATED WITH ANTIPSYCHOTIC USE IN SCHIZOPHRENIA
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Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
adverse effects and with the intention of improving the quality of life of patients and their relationship with their environment Methods: This study started in January 2010, recruiting patients from the Autonomous Region of Madrid. 3.1. Patients To date, participating patients have been > 18 years old and presented with a first acute psychotic episode. They were diagnosed according to DSM-IV criteria and had no personal previous psychiatric history. 3.2. Study design, efficacy and safety evaluation parameters A first multicenter, observational, prospective, openlabel and standard clinical practice12-week study starting at the diagnosis of an acute psychotic episode has been conducted. The patients have been treated paliperidone at flexibles doses Evaluations were performed during the baseline period, and on weeks 2, 4, 8 and 12. At each assessment a clinical interview was conducted together with an evaluation of treatment and treatment adherence, recording of side effects, and psychometric measurements with validated. During the baseline and week 12 interviews, functioning was evaluated using the PSP scale to assess variation in global functioning. Similarly, we monitored physical measurements at baseline and weeks 4 and 12, including blood pressure, heart rate, BMI, abdominal perimeter, ECG, general biochemistry, blood count, and blood prolactin Results: A consistent decrease in PANSS total score up to week (-68 points) has been observed following admission into SSU, clinical evaluation, treatment initiation at week zero with paliperidona at variable doses, association with benzodiazepines and anticholinergics, if required, health education and treatment adherence programme, psychotherapeutic management, and family intervention. The differences are statistically significant (p<0.0001). In addition, the differences in the PANSS subscales scores between baseline and endpoint are clearly smaller following treatment. The differences are statistically significant (p<0.0001) in all cases. In the sample of patients analysed so far, only one patient discontinued treatment as a result of lack of adherence to oral treatment, making parenteral medication necessary. With regard to the PSP scale following the intervention conducted in our unit, significant improvements have been detected in social function between baseline and endpoint (week 12) for the whole group of patients treated up to week 12. Discussion: According to the results obtained in the current study, we can conclude that hospital intervention in early acute phases of disorders within the psychotic spectrum shows clinical effectiveness in the first stages of these disorders. It therefore offers a first line alternative and results in the improvement of personal and social function from baseline.
Poster #215 PREHYPERTENSION, HYPERTENSION, DIABETES, OBESITY AND CARDIOMETABOLIC CHANGES ASSOCIATED WITH ANTIPSYCHOTIC USE IN SCHIZOPHRENIA Sahoo Saddichha 1 , Sayeed Akhtar 2 1 NIMHANS, Bangalore, India; 2 CIP, Ranchi, India Background: Antipsychotic-induced blood pressure and metabolic changes in the treatment of mental illness is one of the biggest challenges being observed in recent times. Previous research studies have been limited by several confounders. This study evaluated the cross-sectional and prospective effects of olanzapine, risperidone and haloperidol on development of prehypertension, hypertension, diabetes, obesity and other metabolic changes in drug-naive patients with first-episode schizophrenia and compared them with a healthy matched control group. Methods: In the first part of the study, a cross-sectional sample of 130 patients on steady doses of antipsychotics was evaluated for the presence of prehypertension, hypertension, DM, obesity and metabolic changes. In the second part, newly diagnosed patients with first-episode schizophrenia, randomized in a double blind trial to be treated with antipsychotic medication – olanzapine, risperidone, or haloperidol – and matched healthy controls were followed for 6 weeks. Body mass index (BMI), blood sugar, blood pressure changes and lipid profile changes were monitored and repeated after 6 weeks. Results: The cross-sectional data revealed a prevalence of obesity in 35.4%, hypertension in 1.5% and metabolic syndrome in 16.2%. In the prospective part, ninety-nine patients with first-episode schizophrenia and 51 healthy controls were examined. Significant changes, between baseline and endpoint, in BMI, serum triglycerides, serum HDL, serum glucose and blood pressure was noted in the patient group (p<0.001) as compared to con-
trol group. Olanzapine (P<0.001) was associated with greater incidence in new onset diabetes, prehypertension and hypertensive changes as well as cardiometabolic changes when compared with risperidone and haloperidol. Discussion: The results confirm clinically significant and substantial changes induced by antipsychotic treatment in drug-naive patients with first-episode schizophrenia and underscore the need to carry out early monitoring of patients on atypical antipsychotics.
Poster #216 RISK OF NEW-ONSET DIABETES AFTER LONG-TERM TREATMENT WITH CLOZAPINE IN COMPARISON TO OTHER ANTIPSYCHOTICS IN PATIENTS WITH SCHIZOPHRENIA Peter F. Schulte 1 , Johanna T. Bocxe 2 , Hieronymus J. Doodeman 2 , Ingrid M. van Haelst 2 , Dan Cohen 1,3 1 Mental Health Services North-Holland-North, Heerhugowaard, North-Holland, Netherlands; 2 Hospital Pharmacy Medical Centre Alkmaar, Alkmaar, North-Holland, Netherlands; 3 Department of Epidemiology Groningen, Groningen, Netherlands Background: Recently, the metabolic side-effects of second generation antipsychotics have become a major concern for clinicians. It has been suggested that olanzapine and clozapine have the highest diabetogenic effect. To confirm these findings we examined the risk of new-onset diabetes of long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Methods: Adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer between 1 November 1994 and 1 January 2010 at the Mental Health Services North-HollandNorth (MHS-NHN) were eligible to participate in the study (index group). The end point of observation was death, loss to follow-up or 1 January 2010. The control group consisted of patients never treated with clozapine. The groups were matched (1:1 ratio) on age (± 3 years), diagnosis and gender. The primary outcome was new-onset diabetes defined as 2 independent fasting glucose measurements of ≥7.0 mmol/L or 2 independent non-fasting glucose measurements of ≥11.1 mmol/L or diagnosis of diabetes in the medical record or treatment with insulin or oral antidiabetics. Secondary outcome was time to new-onset diabetes. We expected a 15% absolute risk increase of new-onset diabetes associated with clozapine. Based on an estimated incidence of 10% in the control group, a significance level of 0.05 and a power of 80%, we needed 96 patients per group. Results: During the study period we identified 94 patients in each group. Seventy-eight point two per cent were men and the mean age when starting clozapine was 39 years (SD 11 years). The mean follow-up in the index and control group was 12.3 and 13.5 years respectively. The vast majority of patients continued clozapine until the end of the follow-up period (mean duration of therapy: 10.7 years). The cumulative incidence of diabetes in the clozapine group was 22.3% compared to 16.0% in the control group (NS). The absolute risk difference was 6.3% (95%CI: -4.9% to 17.5%). The hazard ratio for time to new-onset diabetes was 1.54 (95%CI: 0.80-3.00). Discussion: To the best of our knowledge, this study has the longest follow-up of a sizeable cohort of clozapine users in comparison to matched controls. The absolute risk difference was 6.3% and not significant despite an adequate power and extended follow-up of more than 13 years. Our result is in agreement with four randomized studies with a follow-up varying from 14 weeks up to 9 years: there was no difference between clozapine and other antipsychotics in glucose levels, risk of new-onset diabetes or rate of hyperglycemic treatment. A case-control study matched 7,227 cases of newly treated diabetes by year of birth and gender to 6,780 controls and found no significant association between the incidence of new-onset diabetes and clozapine. Even though we could not prove a significant risk difference for diabetes in a cohort of patients on clozapine in comparison to a cohort on other antipsychotics, the incidence of diabetes was high. On the basis of results from this and earlier studies, clinicians should focus on the prevention and detection of diabetes in all patients with schizophrenia and schizoaffective disorder and routinely monitor weight and metabolic parameters as recommended.
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
adverse effects and with the intention of improving the quality of life of patients and their relationship with their environment Methods: This study started in January 2010, recruiting patients from the Autonomous Region of Madrid. 3.1. Patients To date, participating patients have been > 18 years old and presented with a first acute psychotic episode. They were diagnosed according to DSM-IV criteria and had no personal previous psychiatric history. 3.2. Study design, efficacy and safety evaluation parameters A first multicenter, observational, prospective, openlabel and standard clinical practice12-week study starting at the diagnosis of an acute psychotic episode has been conducted. The patients have been treated paliperidone at flexibles doses Evaluations were performed during the baseline period, and on weeks 2, 4, 8 and 12. At each assessment a clinical interview was conducted together with an evaluation of treatment and treatment adherence, recording of side effects, and psychometric measurements with validated. During the baseline and week 12 interviews, functioning was evaluated using the PSP scale to assess variation in global functioning. Similarly, we monitored physical measurements at baseline and weeks 4 and 12, including blood pressure, heart rate, BMI, abdominal perimeter, ECG, general biochemistry, blood count, and blood prolactin Results: A consistent decrease in PANSS total score up to week (-68 points) has been observed following admission into SSU, clinical evaluation, treatment initiation at week zero with paliperidona at variable doses, association with benzodiazepines and anticholinergics, if required, health education and treatment adherence programme, psychotherapeutic management, and family intervention. The differences are statistically significant (p<0.0001). In addition, the differences in the PANSS subscales scores between baseline and endpoint are clearly smaller following treatment. The differences are statistically significant (p<0.0001) in all cases. In the sample of patients analysed so far, only one patient discontinued treatment as a result of lack of adherence to oral treatment, making parenteral medication necessary. With regard to the PSP scale following the intervention conducted in our unit, significant improvements have been detected in social function between baseline and endpoint (week 12) for the whole group of patients treated up to week 12. Discussion: According to the results obtained in the current study, we can conclude that hospital intervention in early acute phases of disorders within the psychotic spectrum shows clinical effectiveness in the first stages of these disorders. It therefore offers a first line alternative and results in the improvement of personal and social function from baseline.
Poster #215 PREHYPERTENSION, HYPERTENSION, DIABETES, OBESITY AND CARDIOMETABOLIC CHANGES ASSOCIATED WITH ANTIPSYCHOTIC USE IN SCHIZOPHRENIA Sahoo Saddichha 1 , Sayeed Akhtar 2 1 NIMHANS, Bangalore, India; 2 CIP, Ranchi, India Background: Antipsychotic-induced blood pressure and metabolic changes in the treatment of mental illness is one of the biggest challenges being observed in recent times. Previous research studies have been limited by several confounders. This study evaluated the cross-sectional and prospective effects of olanzapine, risperidone and haloperidol on development of prehypertension, hypertension, diabetes, obesity and other metabolic changes in drug-naive patients with first-episode schizophrenia and compared them with a healthy matched control group. Methods: In the first part of the study, a cross-sectional sample of 130 patients on steady doses of antipsychotics was evaluated for the presence of prehypertension, hypertension, DM, obesity and metabolic changes. In the second part, newly diagnosed patients with first-episode schizophrenia, randomized in a double blind trial to be treated with antipsychotic medication – olanzapine, risperidone, or haloperidol – and matched healthy controls were followed for 6 weeks. Body mass index (BMI), blood sugar, blood pressure changes and lipid profile changes were monitored and repeated after 6 weeks. Results: The cross-sectional data revealed a prevalence of obesity in 35.4%, hypertension in 1.5% and metabolic syndrome in 16.2%. In the prospective part, ninety-nine patients with first-episode schizophrenia and 51 healthy controls were examined. Significant changes, between baseline and endpoint, in BMI, serum triglycerides, serum HDL, serum glucose and blood pressure was noted in the patient group (p<0.001) as compared to con-
trol group. Olanzapine (P<0.001) was associated with greater incidence in new onset diabetes, prehypertension and hypertensive changes as well as cardiometabolic changes when compared with risperidone and haloperidol. Discussion: The results confirm clinically significant and substantial changes induced by antipsychotic treatment in drug-naive patients with first-episode schizophrenia and underscore the need to carry out early monitoring of patients on atypical antipsychotics.
Poster #216 RISK OF NEW-ONSET DIABETES AFTER LONG-TERM TREATMENT WITH CLOZAPINE IN COMPARISON TO OTHER ANTIPSYCHOTICS IN PATIENTS WITH SCHIZOPHRENIA Peter F. Schulte 1 , Johanna T. Bocxe 2 , Hieronymus J. Doodeman 2 , Ingrid M. van Haelst 2 , Dan Cohen 1,3 1 Mental Health Services North-Holland-North, Heerhugowaard, North-Holland, Netherlands; 2 Hospital Pharmacy Medical Centre Alkmaar, Alkmaar, North-Holland, Netherlands; 3 Department of Epidemiology Groningen, Groningen, Netherlands Background: Recently, the metabolic side-effects of second generation antipsychotics have become a major concern for clinicians. It has been suggested that olanzapine and clozapine have the highest diabetogenic effect. To confirm these findings we examined the risk of new-onset diabetes of long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Methods: Adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer between 1 November 1994 and 1 January 2010 at the Mental Health Services North-HollandNorth (MHS-NHN) were eligible to participate in the study (index group). The end point of observation was death, loss to follow-up or 1 January 2010. The control group consisted of patients never treated with clozapine. The groups were matched (1:1 ratio) on age (± 3 years), diagnosis and gender. The primary outcome was new-onset diabetes defined as 2 independent fasting glucose measurements of ≥7.0 mmol/L or 2 independent non-fasting glucose measurements of ≥11.1 mmol/L or diagnosis of diabetes in the medical record or treatment with insulin or oral antidiabetics. Secondary outcome was time to new-onset diabetes. We expected a 15% absolute risk increase of new-onset diabetes associated with clozapine. Based on an estimated incidence of 10% in the control group, a significance level of 0.05 and a power of 80%, we needed 96 patients per group. Results: During the study period we identified 94 patients in each group. Seventy-eight point two per cent were men and the mean age when starting clozapine was 39 years (SD 11 years). The mean follow-up in the index and control group was 12.3 and 13.5 years respectively. The vast majority of patients continued clozapine until the end of the follow-up period (mean duration of therapy: 10.7 years). The cumulative incidence of diabetes in the clozapine group was 22.3% compared to 16.0% in the control group (NS). The absolute risk difference was 6.3% (95%CI: -4.9% to 17.5%). The hazard ratio for time to new-onset diabetes was 1.54 (95%CI: 0.80-3.00). Discussion: To the best of our knowledge, this study has the longest follow-up of a sizeable cohort of clozapine users in comparison to matched controls. The absolute risk difference was 6.3% and not significant despite an adequate power and extended follow-up of more than 13 years. Our result is in agreement with four randomized studies with a follow-up varying from 14 weeks up to 9 years: there was no difference between clozapine and other antipsychotics in glucose levels, risk of new-onset diabetes or rate of hyperglycemic treatment. A case-control study matched 7,227 cases of newly treated diabetes by year of birth and gender to 6,780 controls and found no significant association between the incidence of new-onset diabetes and clozapine. Even though we could not prove a significant risk difference for diabetes in a cohort of patients on clozapine in comparison to a cohort on other antipsychotics, the incidence of diabetes was high. On the basis of results from this and earlier studies, clinicians should focus on the prevention and detection of diabetes in all patients with schizophrenia and schizoaffective disorder and routinely monitor weight and metabolic parameters as recommended.