Projects / Programmes
Pharmacogenetics of Antidepressant Drug Treatment
| Code |
Science |
Field |
Subfield |
| 3.09.00 |
Medical sciences |
Psychiatry |
|
| Code |
Science |
Field |
| B650 |
Biomedical sciences |
Psychiatry, clinical psychology, psychosomatics |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
pharmacogenetics, antidepressants, depression, tretment, drug, pharmacoeeconomics
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
28395 |
PhD Matej Kastelic |
Psychiatry |
Head |
2013 - 2015 |
35 |
Organisations (1)
Abstract
Depressive disorders constitute a major public health issue and have been estimated to be the fourth major cause of disability worldwide, and may become second only to cardiovascular diseases until the 2020 according to World Health Organization, Depression is successfully diagnosed in approximately 50% of all cases, of which only 30% are treated with antidepressants (ADs) and psychotherapy. The lack of response to the AD treatment which cannot be predicted, presents a big problem in the antidepressant treatment. Antidepressant therapy is effective only in 60-80% of the patients and 30-40% of the patients do not show a significant response to the first AD prescribed. All ADs have a lag phase and it takes at least 4 weeks to observe some effect of treatment and the response can be evaluated with full certainty only after 3 months of treatment. It can be insufficient due to the lack of treatment response or due to the accuracy of side effects, which can negatively impact the compliance (an average of 65%). The above facts result in overall efficiency of the first AD treatment in only 10-15% of the patients, leading to poor quality of life of the patient, work disability, increased suicide risk and prolonged hospitalization time which consequently reflects in the higher economic burden of the disease. Despite some well-known but unreliable predictors of AD response, such as demographic factors, disease course and social factors, the ADs are still prescribed on the principal of trying. That is why improved prediction of response to AD before treatment would be extremely valuable, from both, clinic as well as economic terms.
We hypothesize that a fast, robust and cost-effective genotyping approach allows early identification of responders to a specific antidepressant treatment and thus improves the treatment efficacy and quality of life for the affected individuals and reduces the health-care costs.
The aim of the study is a comprehensive examination of the simultaneous influence of selected genetic polymorphisms that may affect the pharmacokinetics and pharmacodynamics of selective serotonin reuptake inhibitors (SSRIs) and noradrenergic antidepressants (NAs), and thus verify the hypothesis that they affect the therapeutic response in the antidepressant treatment of the first episode of mood disorders. Repeated clinical assessment of patients with mood disorders/unipolar depression receiving SSRIs or NA treatment prescribed by their general practitioner will be used to evaluate drug response and tolerability. Modern cost-effective genotyping approach will be used to investigate if genetic polymorphisms influencing drug metabolism (CYP2D6, MDR1), the drug target pathway (serotonin synthesis, transport, receptor and signalling) and/or symptomatology of depression (serotonergic pathway, CLOCK gene and others) individually or in synergy modify the response to SSRI.
To assess the cost-benefit of incorporating information from Serotonin transporter gene promoter polymorphism (5-HTTLPR) genetic test in treatment algorithms for depression thus reducing the economic burden of depression on health and society. The study was designed as the first prospective attempt of translating the genotyping for 5-HTTLPR to the clinical practice of treatment with antidepressants in Slovenia. In addition to performing the pharmacoeconomical study of genotyping, we aim to comprehensively examine a wide range of factors which might affect the translation of genotyping in clinical practice In particular we wish to assess the professional and lay understanding of the influence of genetic factors, their relationship to genetic testing and their willingness to introduce it into clinical practice and the evaluation of the performance of the forecast factors.
Results of our study may serve as guidelines in future attempts of translating genotyping in clinical practice.
Significance for science
The study comprehensively examined the simultaneous influence of genetic factors on the response to treatment of depression with an SSRI, in order to identify genetic factors predictive for efficacy of therapy. This applicative study may contribute to more rational and individualized treatment with an SSRI and a better quality of life for patients. An essential and primary benefit of the research is the possibility of the proposed therapeutic effect and possible adverse effects of certain medications for each individual patient. This option would increase the efficacy of psychopharmacological treatment of depression and prevent the prescription of antidepressants which may be ineffective or cause adverse side effects. This would improve the patients remission rate, their quality of life, the treatment’s time period, the amount of drugs prescribed, the number of doctor visits and consequently reduce the costs of pharmacological treatment of depression. The genotyping procedure itself does not present any additional risk to the patient’s health. Our study was a first attempt to translate pharmacogenetic testing for 5-HTTLPR to the clinical practice of pharmacological treatment of depression. Although pharmacogenetics is currently still mainly in the research stage, its use in terms of personalized drug prescription is expected to increase. This would become possible with the development of pharmacogenetic tests which would help doctors prescribe the most effective drugs, which are least likely to cause any adverse events . Therefore treatment could be personalized to each individual, as the same drug or drug dose is not equally effective in all patients due to their genetic variation. However, in order to be promoted as part of the regular clinical practice, this tests should be sufficiently predictive and economically affordable.The present progressive study is the first in Slovenia aiming to obtaine relevant data on the cost-benefit ratio of genotyping for the 5-HTTLPR in the treatment with ADs. This study may continue to serve as a model for evaluating the pharmacoeconomics of genotyping for other predictive factors of different pharmacological treatments. In our opinion the pharmacoeconomic research field will become important in the coming years, as cost effectiveness of any genetic testing would have to be performed prior to successful implementation in the clinical practice. The present prospective study also provided us with some insight into awareness raising in experts as well as the lay publics relationship with genotyping. In our opinion this is besides the reduction of economic burden, an important factor to achive a successful transfer of some promising research findings from the field of pharmacogenetics into clinical practice.
Significance for the country
Depressive disorders constitute a major public health issue and have been estimated to be the fourth major cause of disability worldwide, and may become second only to cardiovascular diseases in the next two decades, thus contributing heavily to the global burden of diseases in man, according to World Health Organization (WHO). Nowadays, at least 20% of the population meets with depression at least once in their lifetime, while 10% of humanity meets with depression regularly. Thus, depression presents increasing social and economic burden in Slovenia as well as in the rest of the world. Due to the large dimensions of the problem the results of our study could have an important impact on the economy and society. The results of the proposed research could significantly increase the efficiency of psychopharmacological treatment of depression which could reflect as: • An increased percentage of patients reaching remission will contribute to higher quality of life for patients with depression, reflecting in increased work capacity and performance, with consequently less sick leaves from work; and thus reduced economic burden on society, • Reduction in medical prescriptions, with consequent lower costs for public health system • Fewer side effects caused by the prescription of unsuitable antidepressant, consequently fewer doctor visits or hospitalizations, reduction in costs for public health system, disburdening of general practitioners, reduction of waiting lists ...
Most important scientific results
Annual report
2014,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
