Kronik Psikiyatrik Hastalıklarda Yeni Deneysel Psikofarmakolojik Çalışmalar
Özet
Dünya Sağlık Örgütü verilerine göre tedavi edilmeyen psikiyatrik bozukluklar küresel hastalık yükünün %13'ünü oluşturmaktadır. Bu alandaki tedavi yetersizliklerini aşmak adına majör depresyon, bipolar bozukluk ve şizofreni gibi kronik hastalıklar üzerinde yeni psikofarmakolojik çalışmalar yürütülmektedir. Majör depresyon tedavisinde, minosiklin ve selekoksib gibi anti-inflamatuar ajanların yanı sıra, özellikle intihar düşüncesini hızla azaltan ve dirençli vakalarda etkinlik gösteren ketamin ile S-ketamin öne çıkmaktadır. Bipolar depresyon alanında ise glutamaterjik sistem üzerinden etki eden riluzol ve ketaminin klinik semptomları hafifletmede başarılı olduğu, dopamin agonistlerinden pramipeksol ile modafinilin de depresyon şiddetini azalttığı gözlemlenmiştir. Şizofreni tedavisinde ise mevcut antipsikotiklerin negatif semptomlardaki yetersizliği nedeniyle NMDA, glisin ve muskarinik reseptörleri hedef alan yeni ajanlar geliştirilmektedir; bu kapsamda ksanomelin-trospium kombinasyonu ve dopamin salınımını düzenleyen bir TAAR-1 agonisti olan SEP-363856 bileşiği, yan etki profillerinin düşüklüğü ve toplam psikopatolojiyi düzeltme potansiyelleriyle geleceğe yönelik ümit verici sonuçlar sunmaktadır.
According to World Health Organization data, untreated psychiatric disorders account for 13% of the global disease burden. To overcome treatment inadequacies in this field, new psychopharmacological studies are being conducted on chronic illnesses such as major depression, bipolar disorder, and schizophrenia. In the treatment of major depression, anti-inflammatory agents like minocycline and celecoxib stand out, alongside ketamine and S-ketamine, which specifically reduce suicidal ideation rapidly and show efficacy in treatment-resistant cases. In the field of bipolar depression, riluzole and ketamine acting through the glutamatergic system have been shown to alleviate clinical symptoms, while dopamine agonists such as pramipexole and modafinil also reduce depression severity. For schizophrenia treatment, due to the insufficiency of current antipsychotics in treating negative symptoms, new agents targeting NMDA, glycine, and muscarinic receptors are being developed; in this context, the xanomeline-trospium combination and the SEP-363856 compound, a TAAR-1 agonist that regulates dopamine release, offer promising results for the future with their low side-effect profiles and potential to improve total psychopathology.
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