THE INFLUENCE OF PHARMACOGENETICS IN THE CLINICAL USE OF ANTIDEPRESSANTS

Öz

The interest on personalized medicine encourages researches on pharmacogenetics. The promotion of new analytical combinations in extensive drug development and also with the progression in the technologies for human gene cloning resulted in a great interest for pharmacogenetics. In last years the development on genetical sciences also influenced pharmacogenetics. Personalized medicine also includes areas such as stratified medicine and precision medicine and these terms are closely related with pharmacogenetics. Moderate response rates and the difference in drug effect on individuals focus pharmacogenetics on psychopharmacology area and antidepressants. It is considered that genetic factors may contribute %50 of antidepressant drug response. Additionally the genetical properties of the patient may effect the pharmacokinetics and pharmacodynamics of the antidepressants therefore the change in the effect and an increase in the side effects may be seen. The genes which codes serotonin transporter, 5-HTTLPR and SLC6A4 are commonly investigated and they are thought to be the main reasons of the difference in antidepressant drug responses. Also the difference in the activities of CYP 2D6 and CYP 2C19 may change the pharmacokinetics of the antidepressants and therefore the stable concentration of antidepressant leves in the plasma. These variations in the factors contributing to the drug levels may lead to a difference in the response rates of antidepressants. In this review, we focused on the pharmacogenetics of different classes of antidepressant drugs such as selective serotonine reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors, tricyclic antidepressants and mono-amine oxidase inhibitors. We have compiled pharmacogenetic studies on antidepressants and effect of genetic variations on the drug responses.

Anahtar Kelimeler

• Antidepressant
• Pharmacogenetics
• Psychopharmacology

FARMAKOGENETİĞİN ANTİDEPRESANLARIN KLİNİK KULLANIMI ÜZERİNE ETKİSİ

Öz

Kişiselleştirilmiş tıbba olan ilgi, farmakogenetik üzerine olan araştırmaları da teşvik etmektedir. İlaç geliştirmede yeni analitik metodların ortaya çıkması ve aynı zamanda insan genom teknolojisinde görülen olumlu gelişmeler araştırmacıların farmakogenetiğe olan ilgisini artırmıştır. Son yıllarda genetik biliminde olan bu tür gelişmeler farmakogenetik bilimine olumlu yönde katkı yapmıştır. Kişileştirilmiş tıp terimi aynı zamanda hedefe yönelik ilaç tedavisi ve kişinin genetiğine göre özel tedavi verme kavramlarını gündeme getirmiştir. İlaç tedavisinde görülen değişik yanıt oranları ve genetik farklılıkların ilaç tedavi başarı oranlarını etkilemesi farmakogenetik çalışmaları, psikofarmakoloji ve antidepresanlar üzerine odaklamıştır. Genetik faktörlerin antidepresan ilaç yanıtına yaklaşık %50 kadar katkısı olabileceği düşünülmektedir. Bunlara ek olarak kişinin genetik faktörleri, antidepresanların farmakokinetik ve farmakodinamik özelliklerini etkileyerek ilacın etki oranlarını değiştirebilir aynı zamanda ilacın kandaki konsantrasyon değişimine bağlı görülebilecek istenmeyen etki sıklığında artışa da sebep olabilmektedir. Serotonin taşıyıcılarını kodlayan genler olan, 5-HTTLPR ve SLC6A4 isimli genler yaygın olarak araştırılmakta ve antidepresan ilaç yanıtında temel farklılıkların bu genlerdeki değişimlerin olduğu sanılmaktadır. Ayrıca CYP 2D6 ve CYP 2C19’un aktivitelerindeki farklılıkların antidepresanların karaciğerdeki yıkım hızını, farmakokinetik özelliklerini etkileyebilmekte ve plazmadaki antidepresan kontsantrasyonlarını değiştirebilmektedir. Tüm bu faktörlerde olabilecek değişiklikler antidepresan tedavisine olan yanıtları değiştirebilmekte ve genetik farklılıklara bağlı doz ayarlaması yapılması gündeme gelmektedir. Bu derlemede, seçici serotonin geri alım inhibitörleri, serotonin-nöradrenalin geri alım inhibitörleri, trisiklik antidepresanlar ve mono-amin oksidaz inhibitörleri gibi farklı antidepresan gruplarının farmakogenetik özelliklerine odaklandık. Genetik varyasyonların, antidepresanların farmakokinetik ve farmakodinamik özellikleri üzerine olan etkilerini ve bu etkilerin antidepresanların kliniğine olan yansımalarını derledik.

Anahtar Kelimeler

• Antidepresanlar
• Farmakogenetik
• Psikofarmakoloji

Kaynakça

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