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Treatment Response in Psychotic Patients in a Naturalistic Setting: Classification, Genes, Drugs, Insight and Social Networks
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Responsible organisation
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many patients with psychotic symptoms respond poorly to treatment. Various approaches have been made to classify these patients according to treatment response. However, existing classifications have been criticized for various reasons and a new classification system is needed. Further, no satisfactory explanation of the poor treatment response has been apparent. The general aim of this thesis was therefore to develop and validate a new classification method of functional remission in a naturalistic population of patients with psychosis and to utilize this classification to investigate the population from genetic, drug treatment, insight and social network points of view.

Data for this cross-sectional study of patients (n=123) attending the Psychosis Outpatient Care clinic in the county of Jönköping, Sweden, were obtained from patient interviews, blood samples and information from patient files. The new classification method CANSEPT, which combines the CAN rating scale (CAN), the UKU side effect rating scale (SE) and the patient’s previous treatment history (PT), showed validity in discriminating the patients and was accepted well by the patients. CANSEPT was used to group the patients in the other studies in this thesis.

The results indicated that the gene polymorphism ABCB1 3435T, was related to worse significant social and clinical needs for patients on olanzapine, while the polymorphism DRD2 Taq1 A1 was related to a greater risk of significant side effects; especially if male, or taking strong dopamine D2-receptor antagonistic drugs. Drug treatment factors were also related to treatment response; longer duration of untreated prodromal and early psychosis was seen for patients with current significant social and clinical needs and non-adherence to treatment was associated with worse significant side effects. Worse treatment outcomes also appeared to be associated with smaller social network groups, worse insight into illness, poorer knowledge of warning signs and worse coping strategies.

In summary, CANSEPT was shown to be a useful valid, multidimensional tool for classification of treatment response. Gene polymorphisms, duration of untreated illness, non-adherence to treatment, social networks and knowledge should be taken into consideration when investigating inadequate treatment response.

Place, publisher, year, edition, pages
Uppsala: Acta Unversitatis Upsaliensis , 2009. , p. 71
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 88
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-9558ISBN: 978-91-554-7414-0 (print)OAI: oai:DiVA.org:uu-9558DiVA, id: diva2:173257
Public defence
2009-03-20, B42, BMC, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2009-02-27 Created: 2009-02-11 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Treatmentresponse in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission
Open this publication in new window or tab >>Treatmentresponse in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission
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2009 (English)In: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 50, no 5, p. 453-462Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. RESULTS: In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. CONCLUSION: In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98078 (URN)10.1016/j.comppsych.2008.11.001 (DOI)000269251100009 ()19683616 (PubMedID)
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2017-12-13Bibliographically approved
2. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting
Open this publication in new window or tab >>Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting
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2008 (English)In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 42, no 11, p. 884-893Article in journal (Refereed) Published
Abstract [en]

RATIONALE: Many patients with psychotic symptoms respond poorly to treatment. Factors possibly affecting treatment response include the presence of polymorphisms in genes coding for various receptor populations, drug-metabolizing enzymes or transport proteins. OBJECTIVES: To investigate whether genetic polymorphisms could be indicators of treatment response to antipsychotic drugs. The genes of interest were the dopamine D2 receptor gene (DRD2), the serotonin 2A and 2C receptor genes (HTR2A and HTR2C), the P-glycoprotein gene (ABCB1 or MDR1) and the drug-metabolizing cytochrome P450 2D6 gene (CYP2D6). MATERIAL AND METHODS: Data for this naturalistic, cross-sectional study of patients requiring antipsychotic drugs and attending the Psychosis Outpatient Care clinic in Jönköping, Sweden were obtained from patient interviews, blood samples and information from patient files. Blood samples were genotyped for DRD2 Taq1 A, Ins/Del and Ser311Cys, HTR2A T102C, HTR2C Cys23Ser, ABCB1 1236C>T, 2677G>T/A, 3435C>T and genetic variants of CYP2D6. The patients (n=116) were grouped according to the CANSEPT method regarding significant social and clinical needs and significant side effects. RESULTS: Patients on olanzapine homozygous for ABCB1 3435T, had more significant social and clinical needs than others. Patients with one or two DRD2 Taq1 A1 alleles had a greater risk of significant side effects, particularly if they were male, Caucasian, had a schizophrenic or delusional disorder or were taking strong dopamine D2-receptor antagonistic drugs. CONCLUSION: If these results are confirmed, patients carrying the DRD2 Taq1 A1 allele would benefit from using drugs without strong dopamine D2 receptor antagonistic properties.

Keywords
DRD2, 5-HT2, ABCB1, Cytochrome P-450 CYP2D6, Antipsychotic agents, Schizophrenia
National Category
Pharmaceutical Sciences Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98079 (URN)10.1016/j.jpsychires.2007.10.007 (DOI)000258798300002 ()18086475 (PubMedID)
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2018-01-13
3. Current and retrospective antipsychotic drug use in relation to treatment response in a naturalistic setting of psychotic patients
Open this publication in new window or tab >>Current and retrospective antipsychotic drug use in relation to treatment response in a naturalistic setting of psychotic patients
2009 (English)Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-98080 (URN)
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2011-05-11Bibliographically approved
4. Knowledge and insight in relation to functional remission in patients with long-term psychotic disorders
Open this publication in new window or tab >>Knowledge and insight in relation to functional remission in patients with long-term psychotic disorders
2010 (English)In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 45, no 5, p. 523-529Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Patients with psychotic symptoms often respond poorly to treatment. Outcomes can be affected by biological, physiological and psychological factors according to the vulnerability-stress model. The patient's coping strategies and beliefs have been correlated with outcomes. OBJECTIVES: To investigate the knowledge and insight in relation to treatment response. METHODS: A naturalistic study was performed using patient interviews and information gathered from patient drug charts. Apart from the rating scales used for classification of treatment response (CANSEPT method), the SPKS knowledge of illness and drugs rating scale was utilized. RESULTS: In the group of patients in functional remission (FR; n = 38), 37% had insight into their illness as compared to 10% among those not in functional remission (non-FR; n = 78; P < 0.01). As much as 23% of the non-FR group had no strategy for responding to warning signs versus 8% in the FR group (P < 0.05). CONCLUSIONS: Better treatment outcomes appear to be associated with better insight into illness, higher knowledge of warning signs and better coping strategies.

Keywords
Health knowledge, Treatment outcome, Schizophrenia, Psychotic disorders, Insight
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-123011 (URN)10.1007/s00127-009-0096-3 (DOI)000275422700002 ()19626260 (PubMedID)
Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2017-12-12Bibliographically approved

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