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P.3.e.016 Humanistic and economic outcomes associated with negative symptoms in patients with schizophrenia
S470
P.3.e Psychotic disorders and antipsychotics – Others (clinical)
P.3.e.015 Psychometric proprieties from the French translation of the “Medication Adherence Rating Scale” (MARS)
to administer since it only contains 10 questions that require “yes” or “no” answers. It has the potential to help clinicians in improving adherence.
D. Misdrahi1 ° , H. Verdoux2 , C. Lan¸con3 , L. Basuyau4 , 1 C.H. Charles Perrens, Departement M. Robin5 , F. Bayl´e5 . de psychiatrie adulte, Bordeaux C´edex, France; 2 C.H. Charles Perrens, Service Universitaire de Psychiatrie, Bordeaux C´edex, France; 3 CHU Ste Marguerite, Service Hospitalo Universitaire de Psychiatrie, Marseille, France; 4 C.H. Charles Perrens, Service Universitaire de Psychiatrie, Bordeaux Cedex, France; 5 C.H. Sainte Anne, Service Hospitalo Universitaire de Sant´e Mentale et de Th´erapeutique, Paris Cedex, France
References
Background: Despite the lack of an accurate definition for adherence and methodological limitations, there is some evidence that almost 50% of all prescriptions are associated with poor adherence with drugs in schizophrenia. It is an identified factor of poor outcome in schizophrenia. Among various methods, self-report questionnaires represent the most cost-effective, less intrusive and time efficient tool to estimate adherence. Thompson et al. [1], have developed the Medication Adherence Rating Scale (MARS) combining items from two existing scales, the Drug Attitude Inventory (DAI) and the 4 items Medication Adherence Questionnaire (MAQ). The MARS has the advantage of recognizing the complexity of adherence since it indicates both problematic behaviors with the questions from the MAQ, along with attitudes towards treatment from items based on the DAI. First objective was to determine the psychometric proprieties of the MARS in it’s French translation form on a sample of inpatients with schizophrenia or schizoaffective disorder. Our further aim was to analyse the specific effects of clinical and sociodemographic variables on the level of adherence. Methods: 92 patients hospitalized with schizophrenia and schizoaffective disorders (DSM IV) were included. Assessment was carried out by a psychiatrist during hospitalization one week before discharge, when the patients were considered to be clinically stable. With the authors’ assent we made two independent translations of the MARS into French (D.M., F.J.B.) to obtain a consensual French language version. An exploratory factor analysis was conducted based on the results from the completed questionnaires and the polychoric correlation matrix on the 10 Items. Internal reliability was assessed using Cronbach’s alpha. Results: Ninety two patients with schizophrenia (n= 63) or shizoaffective disorder with a mean age of 37 years (SD 12.4; range 19−79) participated in this study. Total score from MARS was obtained for 92 patients, with a mean score of 5.4 (SD 2.0; range 1−9). Internal consistency revealed a moderate satisfactory Cronbach’s values for the French version of the MARS (alpha = 0.50). Principal component analysis was carried out on results from the 82 complete questionnaires answered on all items. The scree plot allowed us to clearly identify two factors with relatively high eigenvalues. These two factors accounted for 55% of the variance. No significant correlations were found between the MARS score and age (r = 0.16; p = 0.15) or GAF score (r = −0.02; p = 0.87). Conclusions: Exploratory factor analysis for the French version of the MARS produced two main factors. The first and strongest factor, Factor I, reflects “medication adherence behavior ” corresponding to the four items from MAQ. Factor II relates to “attitude toward medication” and concern 6 items from DAI. The MARS can be administered in any clinical setting and is quick and simple
L. Kleinman1 , S. Mannix2 , O. Leeuwenkamp3 ° , D. Revicki2 , 1 United BioSource Corporation, Seattle, USA; D. Velligan4 . 2 United BioSource Corporation, Bethesda, USA; 3 Organon a part of Schering-Plough Corporation, Oss, The Netherlands; 4 University of Texas Health Science Center at San Antonio, Department of Psychiatry, San Antonio, USA
[1] Thompson, K., Kulkarni, J., Sergejew, A.A. 2000 Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr Res 42, 241–247.
P.3.e.016 Humanistic and economic outcomes associated with negative symptoms in patients with schizophrenia
Objective: Negative symptoms of schizophrenia refer to an absence of or diminution in normal responsiveness. Negative symptoms are manifested as asociality, anhedonia, apathy, flat affect, and impoverished speech. Primary negative symptoms are an intrinsic and persistent clinical dimension of schizophrenia. Deficit syndrome is the term used to describe a distinct clinical condition in patients with schizophrenia in whom disabling primary negative symptoms have persisted for at least 12 months, even during periods of clinical stability. Secondary negative symptoms are those that are attributable to other causes, including unrelieved positive symptoms or adverse events associated with pharmacotherapy, such as extrapyramidal symptoms, and may diminish with improved drug efficacy and tolerability. Our goal was to gain improved understanding of the influence of negative symptoms on humanistic outcomes, including measures of health-related quality of life (HRQL) and patient functioning. Methods: A systematic literature review was conducted of the MEDLINE, EMBASE, PsycINFO, and Cochrane Library databases for articles that discussed humanistic or economic outcomes and their association with negative symptoms in patients with schizophrenia. The search was limited to English language articles published between 1995 and 2005. Search terms included “negative symptoms” in general and specific symptom types (eg, “anhedonia,” etc) as well as outcomes-related terms (eg, “functional status,” “quality of life,” etc). An article or abstract was excluded if it 1) did not specifically address humanistic or economic outcomes in patients with schizophrenia, 2) did not include specific information on the influence of negative symptoms, or 3) did not directly measure the relationship between negative symptoms and these outcome measures. Results: After reviewing more than 600 abstracts, we assessed 182 full-text articles describing humanistic outcomes (n = 149) and economic outcomes (n = 33). After exclusions, 27 humanistic outcomes articles (3 addressing HRQL and 24 addressing functional status) and 5 economic outcomes articles remained. Data from cross-sectional studies and most longitudinal studies supported the association between negative symptoms and reduced HRQL, with statistically significant correlations (r = −0.22 to −0.69, P < 0.05 to P < 0.001) between the presence of negative symptoms and HRQL. Cross-sectional studies also reported greater functional impairment in patients with negative symptoms versus those without negative symptoms ( r = 0.62 to 0.59; P < 0.05 to P < 0.001).
P.3.e Psychotic disorders and antipsychotics – Others (clinical) The limited data on economic outcomes specifically related to negative symptoms revealed a pattern of negative symptoms incrementing direct and indirect costs in patients with schizophrenia. Conclusion: This literature search suggests an association between the presence of negative symptoms and diminished humanistic outcomes in patients with schizophrenia. Although data on economic outcomes are limited, negative symptoms seem to be associated with increased healthcare costs and decreased employment rates. These findings suggest that more effective pharmacologic and psychosocial treatment of negative symptoms in patients with schizophrenia may improve HRQL and functioning and might decrease the overall economic impact of schizophrenia.
P.3.e.017 Biomarkers of oxidative stress in chronically medicated patients, treated with conventional and atypical antipsychotics K. Kosma1 ° , A. Sianni2 , K. Liatsos3 , A. Kontoangelos4 , 1 Dromokaitio C. Leotsakou5 , A. Kalogeropoulou6 . Psychiatric Hospital of Attika, Neurological Department, Athens, Greece; 2 Dromokaitio Psychiatric Hospital of Attika, Department of Internal Medicine, Athens, Greece; 3 Mitera Maternity Hospital of Athens, Department of Gynecology, Athens, Greece; 4 Athens University Medical School Eginition Hospital, Neurological Department, Athens, Greece; 5 Dromokaitio Psychiatric Hospital of Attika, Psychiatric Department, Athens, Greece; 6 Dromokaitio Psychiatric Hospital of Attika, Psychiatric Department, Athens, Greece Introduction: An increasing body of evidence suggests that oxidative damage and impaired antioxidant defence exists in schizophrenia and furthermore these alterations have been postulated as a possible mechanism for neuronal damage associated with tardive dyskinesia in patients that are under prolonged antipsychotic medication. However, some studies conclude that oxidative stress is implicated in the pathogenesis of schizophrenia and others support the fact that neurotoxic free radical production is a consequence of antipsychotic treatment. In addition, the results of some recent short-term treatment studies suggest that atypical antipsychotics compared to the conventional ones have neuroprotective effects. Aim: The aim of the present study was to examine the effect of long term medication in the oxidative defence system of all patients receiving antipsychotic agents and to investigate if any differences exist between patients receiving conventional or atypical antipsychotics Subjects and Methods: In total, 85 patients (45 men and 40 women) were enrolled in the study. Mean age 55±3 years, and the mean duration of illness was 25±5 years. 63 were diagnosed with schizophrenia, 14 with schizoaffective disorder and 9 with bipolar disorder according to the DSM-IV diagnostic criteria for mental disorders. 25 patients, (Group A) were receiving conventional antipsychotics and the rest, (Group B) were receiving atypical antipsychotics. Total Antioxidant Status (TAS) and the levels of a key antioxidant enzyme, namely glutathione peroxidase (GSHPx) were counted in the serum of participants with an OLYMPUS AU400 analyser, using the commercial kits of RANDOX according to the manufacturer procedures. The results of both groups were compared with each other. Results: For Group A, TAS levels were 1.53±0.18 mmol/lt and GSH-Px was 47.50±10.58U/lt. Among patients of Group B, TAS was 1.59±0.17 mmol/lt and GSH-Px was 51.41±10.80U/lt. The statistical analysis revealed that the serum values of TAS and
S471
GSH-Px for Group A were lower in comparison with Group B (p = 0.35 and p = 0.23 respectively). However these differences did not reach a statistical difference which means that there was no difference between patients receiving conventional and atypical neuroleptics. Conclusions: The results of the present study support the fact that long term antipsychotic medication is related and may in fact be responsible for oxidative damage in all patients regardless of the diagnosis. Additionally, the study revealed that no difference was noted between patients receiving conventional or atypical antipsychotics. This finding contrasts the result of similar studies that newer antipsychotic agents may have even neuroprotective effects, so it is reasonable to assume that this might be due to the prolonged duration of treatment in our sample. Furthermore, since antioxidant defence system alterations have been postulated as a possible mechanism for neuronal damage, other clinical trials are needed to ascertain the role of antioxidants and the value of antioxidant supplementation in preventive and early intervention approaches in populations at risk.
P.3.e.018 Antipsychotic preparation and schizophrenia relapse risk: a one-year survey in a naturalistic setting J.C. Leuvennink1 ° , D.J. Hall1 , K. Frew1 . 1 Crichton Royal Hospital, Psychiatry, Dumfries, United Kingdom Purpose: We aimed to identify whether the antipsychotic preparation, oral or long acting intramuscular, correlates with psychotic relapse rates in patients who suffer from schizophrenia. Methods: We endeavoured to do a retrospective survey of relapse rates of all patients between 18 and 65 years old known to suffer from schizophrenia within the defined geographical area of Dumfries and Nithsdale, South-west Scotland. Owing to national standards for the treatment of patients suffering from schizophrenia in Scotland, all those suffering from this disorder who are known to the service will continue to receive treatment and support from psychiatric services in the National Health Service. Patients in Scotland are registered with general practitioners and general practices are aligned with secondary care mental health services in such a way that good communication and seamless care can be provided to the individual patients. The above allows for accurate and appropriate audits of their treatment. This survey was therefore done in a naturalistic setting with a high degree of accuracy of data for reasons explained. Among these patients, we identified those treated with oral, and those treated with long acting intramuscular antipsychotic preparations. Almost all patients who suffer an acute psychotic relapse in this region will come into contact with either acute psychiatric inpatient services or the Crisis Assessment and Treatment Service. We therefore were able to collect data from the above services on patients with schizophrenia who suffered psychotic relapses over a one year period. We excluded those who came into contact with these services for reasons of social crisis or a second diagnosis, and recurrent relapses. We then compared the relapse rates of those patients on oral antipsychotic preparations with those on long acting intramuscular preparations. Results: In this geographical area with a younger adult population (18−65 years) of 33,524, we identified 144 patients with a diagnosis of schizophrenia. Of those, 103 were prescribed oral antipsychotic medication and 41 long acting intramuscular antipsychotic preparations. The overall relapse rate over the year
P.3.e Psychotic disorders and antipsychotics – Others (clinical)
P.3.e.015 Psychometric proprieties from the French translation of the “Medication Adherence Rating Scale” (MARS)
to administer since it only contains 10 questions that require “yes” or “no” answers. It has the potential to help clinicians in improving adherence.
D. Misdrahi1 ° , H. Verdoux2 , C. Lan¸con3 , L. Basuyau4 , 1 C.H. Charles Perrens, Departement M. Robin5 , F. Bayl´e5 . de psychiatrie adulte, Bordeaux C´edex, France; 2 C.H. Charles Perrens, Service Universitaire de Psychiatrie, Bordeaux C´edex, France; 3 CHU Ste Marguerite, Service Hospitalo Universitaire de Psychiatrie, Marseille, France; 4 C.H. Charles Perrens, Service Universitaire de Psychiatrie, Bordeaux Cedex, France; 5 C.H. Sainte Anne, Service Hospitalo Universitaire de Sant´e Mentale et de Th´erapeutique, Paris Cedex, France
References
Background: Despite the lack of an accurate definition for adherence and methodological limitations, there is some evidence that almost 50% of all prescriptions are associated with poor adherence with drugs in schizophrenia. It is an identified factor of poor outcome in schizophrenia. Among various methods, self-report questionnaires represent the most cost-effective, less intrusive and time efficient tool to estimate adherence. Thompson et al. [1], have developed the Medication Adherence Rating Scale (MARS) combining items from two existing scales, the Drug Attitude Inventory (DAI) and the 4 items Medication Adherence Questionnaire (MAQ). The MARS has the advantage of recognizing the complexity of adherence since it indicates both problematic behaviors with the questions from the MAQ, along with attitudes towards treatment from items based on the DAI. First objective was to determine the psychometric proprieties of the MARS in it’s French translation form on a sample of inpatients with schizophrenia or schizoaffective disorder. Our further aim was to analyse the specific effects of clinical and sociodemographic variables on the level of adherence. Methods: 92 patients hospitalized with schizophrenia and schizoaffective disorders (DSM IV) were included. Assessment was carried out by a psychiatrist during hospitalization one week before discharge, when the patients were considered to be clinically stable. With the authors’ assent we made two independent translations of the MARS into French (D.M., F.J.B.) to obtain a consensual French language version. An exploratory factor analysis was conducted based on the results from the completed questionnaires and the polychoric correlation matrix on the 10 Items. Internal reliability was assessed using Cronbach’s alpha. Results: Ninety two patients with schizophrenia (n= 63) or shizoaffective disorder with a mean age of 37 years (SD 12.4; range 19−79) participated in this study. Total score from MARS was obtained for 92 patients, with a mean score of 5.4 (SD 2.0; range 1−9). Internal consistency revealed a moderate satisfactory Cronbach’s values for the French version of the MARS (alpha = 0.50). Principal component analysis was carried out on results from the 82 complete questionnaires answered on all items. The scree plot allowed us to clearly identify two factors with relatively high eigenvalues. These two factors accounted for 55% of the variance. No significant correlations were found between the MARS score and age (r = 0.16; p = 0.15) or GAF score (r = −0.02; p = 0.87). Conclusions: Exploratory factor analysis for the French version of the MARS produced two main factors. The first and strongest factor, Factor I, reflects “medication adherence behavior ” corresponding to the four items from MAQ. Factor II relates to “attitude toward medication” and concern 6 items from DAI. The MARS can be administered in any clinical setting and is quick and simple
L. Kleinman1 , S. Mannix2 , O. Leeuwenkamp3 ° , D. Revicki2 , 1 United BioSource Corporation, Seattle, USA; D. Velligan4 . 2 United BioSource Corporation, Bethesda, USA; 3 Organon a part of Schering-Plough Corporation, Oss, The Netherlands; 4 University of Texas Health Science Center at San Antonio, Department of Psychiatry, San Antonio, USA
[1] Thompson, K., Kulkarni, J., Sergejew, A.A. 2000 Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr Res 42, 241–247.
P.3.e.016 Humanistic and economic outcomes associated with negative symptoms in patients with schizophrenia
Objective: Negative symptoms of schizophrenia refer to an absence of or diminution in normal responsiveness. Negative symptoms are manifested as asociality, anhedonia, apathy, flat affect, and impoverished speech. Primary negative symptoms are an intrinsic and persistent clinical dimension of schizophrenia. Deficit syndrome is the term used to describe a distinct clinical condition in patients with schizophrenia in whom disabling primary negative symptoms have persisted for at least 12 months, even during periods of clinical stability. Secondary negative symptoms are those that are attributable to other causes, including unrelieved positive symptoms or adverse events associated with pharmacotherapy, such as extrapyramidal symptoms, and may diminish with improved drug efficacy and tolerability. Our goal was to gain improved understanding of the influence of negative symptoms on humanistic outcomes, including measures of health-related quality of life (HRQL) and patient functioning. Methods: A systematic literature review was conducted of the MEDLINE, EMBASE, PsycINFO, and Cochrane Library databases for articles that discussed humanistic or economic outcomes and their association with negative symptoms in patients with schizophrenia. The search was limited to English language articles published between 1995 and 2005. Search terms included “negative symptoms” in general and specific symptom types (eg, “anhedonia,” etc) as well as outcomes-related terms (eg, “functional status,” “quality of life,” etc). An article or abstract was excluded if it 1) did not specifically address humanistic or economic outcomes in patients with schizophrenia, 2) did not include specific information on the influence of negative symptoms, or 3) did not directly measure the relationship between negative symptoms and these outcome measures. Results: After reviewing more than 600 abstracts, we assessed 182 full-text articles describing humanistic outcomes (n = 149) and economic outcomes (n = 33). After exclusions, 27 humanistic outcomes articles (3 addressing HRQL and 24 addressing functional status) and 5 economic outcomes articles remained. Data from cross-sectional studies and most longitudinal studies supported the association between negative symptoms and reduced HRQL, with statistically significant correlations (r = −0.22 to −0.69, P < 0.05 to P < 0.001) between the presence of negative symptoms and HRQL. Cross-sectional studies also reported greater functional impairment in patients with negative symptoms versus those without negative symptoms ( r = 0.62 to 0.59; P < 0.05 to P < 0.001).
P.3.e Psychotic disorders and antipsychotics – Others (clinical) The limited data on economic outcomes specifically related to negative symptoms revealed a pattern of negative symptoms incrementing direct and indirect costs in patients with schizophrenia. Conclusion: This literature search suggests an association between the presence of negative symptoms and diminished humanistic outcomes in patients with schizophrenia. Although data on economic outcomes are limited, negative symptoms seem to be associated with increased healthcare costs and decreased employment rates. These findings suggest that more effective pharmacologic and psychosocial treatment of negative symptoms in patients with schizophrenia may improve HRQL and functioning and might decrease the overall economic impact of schizophrenia.
P.3.e.017 Biomarkers of oxidative stress in chronically medicated patients, treated with conventional and atypical antipsychotics K. Kosma1 ° , A. Sianni2 , K. Liatsos3 , A. Kontoangelos4 , 1 Dromokaitio C. Leotsakou5 , A. Kalogeropoulou6 . Psychiatric Hospital of Attika, Neurological Department, Athens, Greece; 2 Dromokaitio Psychiatric Hospital of Attika, Department of Internal Medicine, Athens, Greece; 3 Mitera Maternity Hospital of Athens, Department of Gynecology, Athens, Greece; 4 Athens University Medical School Eginition Hospital, Neurological Department, Athens, Greece; 5 Dromokaitio Psychiatric Hospital of Attika, Psychiatric Department, Athens, Greece; 6 Dromokaitio Psychiatric Hospital of Attika, Psychiatric Department, Athens, Greece Introduction: An increasing body of evidence suggests that oxidative damage and impaired antioxidant defence exists in schizophrenia and furthermore these alterations have been postulated as a possible mechanism for neuronal damage associated with tardive dyskinesia in patients that are under prolonged antipsychotic medication. However, some studies conclude that oxidative stress is implicated in the pathogenesis of schizophrenia and others support the fact that neurotoxic free radical production is a consequence of antipsychotic treatment. In addition, the results of some recent short-term treatment studies suggest that atypical antipsychotics compared to the conventional ones have neuroprotective effects. Aim: The aim of the present study was to examine the effect of long term medication in the oxidative defence system of all patients receiving antipsychotic agents and to investigate if any differences exist between patients receiving conventional or atypical antipsychotics Subjects and Methods: In total, 85 patients (45 men and 40 women) were enrolled in the study. Mean age 55±3 years, and the mean duration of illness was 25±5 years. 63 were diagnosed with schizophrenia, 14 with schizoaffective disorder and 9 with bipolar disorder according to the DSM-IV diagnostic criteria for mental disorders. 25 patients, (Group A) were receiving conventional antipsychotics and the rest, (Group B) were receiving atypical antipsychotics. Total Antioxidant Status (TAS) and the levels of a key antioxidant enzyme, namely glutathione peroxidase (GSHPx) were counted in the serum of participants with an OLYMPUS AU400 analyser, using the commercial kits of RANDOX according to the manufacturer procedures. The results of both groups were compared with each other. Results: For Group A, TAS levels were 1.53±0.18 mmol/lt and GSH-Px was 47.50±10.58U/lt. Among patients of Group B, TAS was 1.59±0.17 mmol/lt and GSH-Px was 51.41±10.80U/lt. The statistical analysis revealed that the serum values of TAS and
S471
GSH-Px for Group A were lower in comparison with Group B (p = 0.35 and p = 0.23 respectively). However these differences did not reach a statistical difference which means that there was no difference between patients receiving conventional and atypical neuroleptics. Conclusions: The results of the present study support the fact that long term antipsychotic medication is related and may in fact be responsible for oxidative damage in all patients regardless of the diagnosis. Additionally, the study revealed that no difference was noted between patients receiving conventional or atypical antipsychotics. This finding contrasts the result of similar studies that newer antipsychotic agents may have even neuroprotective effects, so it is reasonable to assume that this might be due to the prolonged duration of treatment in our sample. Furthermore, since antioxidant defence system alterations have been postulated as a possible mechanism for neuronal damage, other clinical trials are needed to ascertain the role of antioxidants and the value of antioxidant supplementation in preventive and early intervention approaches in populations at risk.
P.3.e.018 Antipsychotic preparation and schizophrenia relapse risk: a one-year survey in a naturalistic setting J.C. Leuvennink1 ° , D.J. Hall1 , K. Frew1 . 1 Crichton Royal Hospital, Psychiatry, Dumfries, United Kingdom Purpose: We aimed to identify whether the antipsychotic preparation, oral or long acting intramuscular, correlates with psychotic relapse rates in patients who suffer from schizophrenia. Methods: We endeavoured to do a retrospective survey of relapse rates of all patients between 18 and 65 years old known to suffer from schizophrenia within the defined geographical area of Dumfries and Nithsdale, South-west Scotland. Owing to national standards for the treatment of patients suffering from schizophrenia in Scotland, all those suffering from this disorder who are known to the service will continue to receive treatment and support from psychiatric services in the National Health Service. Patients in Scotland are registered with general practitioners and general practices are aligned with secondary care mental health services in such a way that good communication and seamless care can be provided to the individual patients. The above allows for accurate and appropriate audits of their treatment. This survey was therefore done in a naturalistic setting with a high degree of accuracy of data for reasons explained. Among these patients, we identified those treated with oral, and those treated with long acting intramuscular antipsychotic preparations. Almost all patients who suffer an acute psychotic relapse in this region will come into contact with either acute psychiatric inpatient services or the Crisis Assessment and Treatment Service. We therefore were able to collect data from the above services on patients with schizophrenia who suffered psychotic relapses over a one year period. We excluded those who came into contact with these services for reasons of social crisis or a second diagnosis, and recurrent relapses. We then compared the relapse rates of those patients on oral antipsychotic preparations with those on long acting intramuscular preparations. Results: In this geographical area with a younger adult population (18−65 years) of 33,524, we identified 144 patients with a diagnosis of schizophrenia. Of those, 103 were prescribed oral antipsychotic medication and 41 long acting intramuscular antipsychotic preparations. The overall relapse rate over the year