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Poster #S9 ELECTRONIC MEASUREMENT OF MOVEMENT DISORDERS: VALIDITY AND RELIABILITY
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
study. Blood was sampled in the fasting state and 90 min after ingestion of a standardized liquid meal (2,268 kJ). Results: Compared to healthy controls, patients were characterized by elevated fasting levels of glucose, proinsulin, C-peptide and glucose-dependent insulinotropic polypeptide (GIP) and higher postprandial levels of insulin, proinsulin, C-peptide and GIP. Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-alpha, plasminogen activator inhibitor 1, interleukin 6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin and adiponectin did not differ between groups. Discussion: Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, non-diabetic antipsychotictreated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite regulating hormones, GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology behind metabolic side-effects of antipsychotics, and put emphasis on the importance of implementing metabolic screening into psychiatric practice.
Poster #S9 ELECTRONIC MEASUREMENT OF MOVEMENT DISORDERS: VALIDITY AND RELIABILITY Thierry Q. Mentzel 1,2 , Charlie Mentzel 1 , Ritsaert Lieverse 2 , Hein Daanen 3 , Peter van Harten 1 1 GGz Centraal; 2 Maastricht University; 3 TNO Background: When treating psychotic disorders it is important to determine the optimal antipsychotic dose for a patient. An optimal dose can improve medication compliance and reduce the discomfort and stigmatization associated with movement disorders (Caliguiri et. al., 2006). Subclinical bradykinesia could be a valid measure for the optimal antipsychotic dose. This idea is based on the findings that antipsychotics are effective at a D2 receptor occupancy above 65%, and that up until a D2 receptor occupancy of 80%, bradykinesia does not occur or merely in a very subtle form (Seeman, 2002). Rating scales are the conventional method of assessing bradykinesia in a clinical setting, for example the Unified Parkinson Disease Rating scale (UPDRS). However, due to their limited sensitivity rating scales are not well suited to measure subtle forms of bradykinesia, furthermore, to achieve a good inter-rater reliability intensive training is required. Electronic movement registration might offer a solution for measuring subtle forms of bradykinesia, because it is potentially more sensitive, more reliable and less subjective than observer based rating scales. The aim of this study is to determine the validity and reliability of an electronic device that measures bradykinesia. Methods: 75 patients treated at GGz centraal (Amersfoort, The Netherlands) will be included. Included are patients treated for psychotic symptoms with antipsychotic medication. The validity is determined by comparing the rating on the UPDRS with the score based on the electronic measurement. The reliability is determined by comparing the scores of the electronic device in 25 randomly selected patients with the scores on a second electronic measurement administered a day later. The electronic measurement consists of four tasks; walking, elbow flexion/extension, lower arm pronation/supination and a leg agility task. The selection of tasks is based on a pilot study we performed (Mentzel et. al., 2013). Movements are captured using six inertial sensors (XSENS, Enschede, The Netherlands) attached to the upper and lower arm, the upper and lower leg and the lower back using velcro straps. Results: At the time of submission 66 of the 75 patients are included. The final results on the validity and reliability of this electronic device that measures bradykinesia will be presented at the conference. Discussion: The discussion and conclusion will be presented at the conference.
S91
Poster #S10 POLYPHARMACY TO COUNTERACT ANTIPSYCHOTIC-INDUCED WEIGHT GAIN AND METABOLIC ADVERSE EFFECTS IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS Yuya Mizuno 1 , Takefumi Suzuki 2 , Atsuo Nakagawa 3 , Kazunari Yoshida 4 , Masaru Mimura 5 , W. Wolfgang Fleischhacker 5 , Hiroyuki Uchida 4 1 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 2 Keio University School of Medicine; 3 Center for Clinical Research, Keio University School of Medicine; 4 Department of Neuropsychiatry, Keio University School of Medicine; 5 Medical University Innsbruck, Austria, Department of Psychiatry and Psychotherapy Background: Data regarding effective strategies to manage antipsychoticinduced metabolic adverse effects are limited. Using concomitant medications to counteract these adverse effects may be a rational option. We performed a systematic review and meta-analysis regarding the effectiveness of medications to counteract antipsychotic-induced metabolic adverse effects in patients with schizophrenia. Methods: Published articles from 1950 to September 2013 were searched using EMBASE, MEDLINE, PsycINFO, PubMed, and the Cochrane Library. Clinical trial registries were searched for unpublished trials. Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they reported on changes in antipsychotic-induced metabolic adverse effects using concomitant medications as a primary outcome. Two independent authors extracted variables related to participants, interventions, comparisons, outcomes and study design. For continuous outcomes, the inverse variance statistical method and random effects model were used to calculate mean differences. For dichotomous outcomes, the Mantel-Haenszel statistical method and random effects model were used to determine odds ratios. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. Results: From the initial list of 1092 records, 40 published and 7 unpublished studies were identified; of these, 39 trials representing 19 unique interventions were included in this meta-analysis. Concomitant metformin was the most extensively studied drug in regards to body weight, with a mean difference of -3.17kg (95% confidence interval: -4.44 to -1.90kg) compared to placebo; however, results were highly heterogeneous (I2 =88%). Synthesized effects for topiramate, sibutramine, aripiprazole and reboxetine were also significant. Metformin was the only drug with evidence of clinically relevant weight change in both prevention and treatment studies. Taking together the limited data in regards to glucose metabolism and blood lipids, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin and sibutramine decreased blood lipids. Discussion: Although additional drug costs, side effects of concomitant drugs themselves, possibility of drug interactions, and paucity of data regarding certain interventions need to be taken into account, polypharmacy in this context may warrant a prudent individualized consideration. The current evidence points to a possible use of adjunctive metformin in order to counteract weight gain and other metabolic adversities with ongoing antipsychotic treatment in schizophrenia.
Poster #S11 THE JOINT EFFECT OF SOCIAL ADVERSITY IN CHILDHOOD AND IN ADULTHOOD ON PREDICTING PSYCHOSIS Simona A. Stilo 1 , Marta Di Forti 1 , Charlotte Gayer-Anderson 1 , Kathryn Hubbard 2 , Ulrich Reininghaus 1 , Antonella Trotta 1 , Stephanie Beards 1 , Helen Fisher 1 , Valeria Mondelli 3 , Robin M. Murray 4 , Craig Morgan 4 1 Institute of Psychiatry, King’s College London; 2 Centre for Epidemiology and Public Mental Health, Health Service and Population Research Department, Institute of Psychiatry, King’s College London; 3 Psychological Medicine, Institute of Psychiatry, King’s College London; 4 IOP Background: There is robust evidence that social adversity in childhood and in adulthood are separately associated with an increased risk of psychosis (Agid O et al. 1999, Morgan C et al. 2008, Stilo S. et al. 2012). We moved beyond the study of each exposure separately by looking at synergistic
study. Blood was sampled in the fasting state and 90 min after ingestion of a standardized liquid meal (2,268 kJ). Results: Compared to healthy controls, patients were characterized by elevated fasting levels of glucose, proinsulin, C-peptide and glucose-dependent insulinotropic polypeptide (GIP) and higher postprandial levels of insulin, proinsulin, C-peptide and GIP. Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-alpha, plasminogen activator inhibitor 1, interleukin 6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin and adiponectin did not differ between groups. Discussion: Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, non-diabetic antipsychotictreated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite regulating hormones, GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology behind metabolic side-effects of antipsychotics, and put emphasis on the importance of implementing metabolic screening into psychiatric practice.
Poster #S9 ELECTRONIC MEASUREMENT OF MOVEMENT DISORDERS: VALIDITY AND RELIABILITY Thierry Q. Mentzel 1,2 , Charlie Mentzel 1 , Ritsaert Lieverse 2 , Hein Daanen 3 , Peter van Harten 1 1 GGz Centraal; 2 Maastricht University; 3 TNO Background: When treating psychotic disorders it is important to determine the optimal antipsychotic dose for a patient. An optimal dose can improve medication compliance and reduce the discomfort and stigmatization associated with movement disorders (Caliguiri et. al., 2006). Subclinical bradykinesia could be a valid measure for the optimal antipsychotic dose. This idea is based on the findings that antipsychotics are effective at a D2 receptor occupancy above 65%, and that up until a D2 receptor occupancy of 80%, bradykinesia does not occur or merely in a very subtle form (Seeman, 2002). Rating scales are the conventional method of assessing bradykinesia in a clinical setting, for example the Unified Parkinson Disease Rating scale (UPDRS). However, due to their limited sensitivity rating scales are not well suited to measure subtle forms of bradykinesia, furthermore, to achieve a good inter-rater reliability intensive training is required. Electronic movement registration might offer a solution for measuring subtle forms of bradykinesia, because it is potentially more sensitive, more reliable and less subjective than observer based rating scales. The aim of this study is to determine the validity and reliability of an electronic device that measures bradykinesia. Methods: 75 patients treated at GGz centraal (Amersfoort, The Netherlands) will be included. Included are patients treated for psychotic symptoms with antipsychotic medication. The validity is determined by comparing the rating on the UPDRS with the score based on the electronic measurement. The reliability is determined by comparing the scores of the electronic device in 25 randomly selected patients with the scores on a second electronic measurement administered a day later. The electronic measurement consists of four tasks; walking, elbow flexion/extension, lower arm pronation/supination and a leg agility task. The selection of tasks is based on a pilot study we performed (Mentzel et. al., 2013). Movements are captured using six inertial sensors (XSENS, Enschede, The Netherlands) attached to the upper and lower arm, the upper and lower leg and the lower back using velcro straps. Results: At the time of submission 66 of the 75 patients are included. The final results on the validity and reliability of this electronic device that measures bradykinesia will be presented at the conference. Discussion: The discussion and conclusion will be presented at the conference.
S91
Poster #S10 POLYPHARMACY TO COUNTERACT ANTIPSYCHOTIC-INDUCED WEIGHT GAIN AND METABOLIC ADVERSE EFFECTS IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND META-ANALYSIS Yuya Mizuno 1 , Takefumi Suzuki 2 , Atsuo Nakagawa 3 , Kazunari Yoshida 4 , Masaru Mimura 5 , W. Wolfgang Fleischhacker 5 , Hiroyuki Uchida 4 1 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 2 Keio University School of Medicine; 3 Center for Clinical Research, Keio University School of Medicine; 4 Department of Neuropsychiatry, Keio University School of Medicine; 5 Medical University Innsbruck, Austria, Department of Psychiatry and Psychotherapy Background: Data regarding effective strategies to manage antipsychoticinduced metabolic adverse effects are limited. Using concomitant medications to counteract these adverse effects may be a rational option. We performed a systematic review and meta-analysis regarding the effectiveness of medications to counteract antipsychotic-induced metabolic adverse effects in patients with schizophrenia. Methods: Published articles from 1950 to September 2013 were searched using EMBASE, MEDLINE, PsycINFO, PubMed, and the Cochrane Library. Clinical trial registries were searched for unpublished trials. Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they reported on changes in antipsychotic-induced metabolic adverse effects using concomitant medications as a primary outcome. Two independent authors extracted variables related to participants, interventions, comparisons, outcomes and study design. For continuous outcomes, the inverse variance statistical method and random effects model were used to calculate mean differences. For dichotomous outcomes, the Mantel-Haenszel statistical method and random effects model were used to determine odds ratios. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. Results: From the initial list of 1092 records, 40 published and 7 unpublished studies were identified; of these, 39 trials representing 19 unique interventions were included in this meta-analysis. Concomitant metformin was the most extensively studied drug in regards to body weight, with a mean difference of -3.17kg (95% confidence interval: -4.44 to -1.90kg) compared to placebo; however, results were highly heterogeneous (I2 =88%). Synthesized effects for topiramate, sibutramine, aripiprazole and reboxetine were also significant. Metformin was the only drug with evidence of clinically relevant weight change in both prevention and treatment studies. Taking together the limited data in regards to glucose metabolism and blood lipids, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin and sibutramine decreased blood lipids. Discussion: Although additional drug costs, side effects of concomitant drugs themselves, possibility of drug interactions, and paucity of data regarding certain interventions need to be taken into account, polypharmacy in this context may warrant a prudent individualized consideration. The current evidence points to a possible use of adjunctive metformin in order to counteract weight gain and other metabolic adversities with ongoing antipsychotic treatment in schizophrenia.
Poster #S11 THE JOINT EFFECT OF SOCIAL ADVERSITY IN CHILDHOOD AND IN ADULTHOOD ON PREDICTING PSYCHOSIS Simona A. Stilo 1 , Marta Di Forti 1 , Charlotte Gayer-Anderson 1 , Kathryn Hubbard 2 , Ulrich Reininghaus 1 , Antonella Trotta 1 , Stephanie Beards 1 , Helen Fisher 1 , Valeria Mondelli 3 , Robin M. Murray 4 , Craig Morgan 4 1 Institute of Psychiatry, King’s College London; 2 Centre for Epidemiology and Public Mental Health, Health Service and Population Research Department, Institute of Psychiatry, King’s College London; 3 Psychological Medicine, Institute of Psychiatry, King’s College London; 4 IOP Background: There is robust evidence that social adversity in childhood and in adulthood are separately associated with an increased risk of psychosis (Agid O et al. 1999, Morgan C et al. 2008, Stilo S. et al. 2012). We moved beyond the study of each exposure separately by looking at synergistic