Ketamin ve Esketaminin Tedaviye Dirençli Depresyonda Bilişsel İşlevler Üzerindeki Etkileri

Yıl 2025, Cilt: 17 Sayı: 3, 493 - 506

Mahir Mutlu , Çağrı Öven , Bilge Sena Kurt , Emre Sunay

https://doi.org/10.18863/pgy.1524106

Öz

Majör depresif bozukluk, yaşam kalitesini olumsuz etkileyen ve bilişsel bozulmalara yol açarak iş, eğitim ve sosyal yaşamda ciddi aksaklıklara neden olan bir halk sağlığı sorunudur. Tedaviye dirençli depresyon, en az iki farklı antidepresan ilacın yeterli süre ve dozda kullanımına rağmen depresyon belirtilerinde iyileşme sağlanamaması durumudur. Mevcut farmakolojik yaklaşımlar, tedaviye dirençli depresyon hastalarının yarısında yetersiz kalmakta ve bu ilaçların bilişsel bozulmalar üzerindeki etkileri sınırlı kalmaktadır. Dolayısıyla, yeni ve etkili tedavi yöntemlerine ihtiyaç duyulmaktadır. Bu derlemenin amacı, tedaviye dirençli depresyon hastalarının tedavisinde kullanılan ketamin ve esketaminin bilişsel fonksiyonlar üzerindeki etkilerini değerlendirmektir. Bu bağlamda gerekli alan yazın incelenmiş ve güncel çalışmalar değerlendirilmiştir. Randomize kontrollü çalışmaların sonuçları, ketaminin tedaviye dirençli depresyon tedavisinde etkili olduğunu ve belirli bilişsel alanlarda iyileşme sağlayabileceğini göstermektedir. Özellikle 0.5 mg/kg ketamin infüzyonuna yanıt veren hastalarda görsel bellek, işleme hızı, çalışma belleği ve dikkat gibi bilişsel işlevlerde anlamlı iyileşmeler kaydedilmiştir. Ancak, uzun süreli ketamin kullanımının mekânsal işlem belleği üzerinde olumsuz etkileri olabileceği belirtilmiştir. Esketamin ise NMDA reseptör antagonisti olarak hızlı ve etkili antidepresan sonuçlar elde etmiş, bilişsel işlevlerde stabilite veya iyileşme sağlamıştır. Ayrıca, intranazal uygulanabilirliği de pratik bir avantaj sunmaktadır. Ancak, yüksek dozda esketamin kullanımının nörotoksik etkiler ve bilişsel işlevler üzerinde olumsuz etkiler yaratabileceğine dair bulgular vardır. Her iki ilacın da depresyon semptomları ve bilişsel işlevler üzerindeki etkileri doz, kullanım süresi ve uygulama sıklığına bağlı olarak değişiklik göstermektedir. Sonuç olarak, ketamin ve esketaminin tedaviye dirençli depresyon tedavisinde ve bilişsel semptomların düzelmesinde önemli bir potansiyele sahip olduğu görülmekle birlikte, uzun vadeli etkiler ve güvenilirlik konusunda daha fazla araştırma gerekmektedir.

Anahtar Kelimeler

Tedaviye Dirençli Depresyon, Ketamin, Esketamin, Bilişsel Fonksiyonlar

Effects of Ketamine and Esketamine on Cognitive Functions in Treatment-Resistant Depression

Öz

Major depressive disorder is a public health issue that negatively impacts quality of life and leads to cognitive impairments, causing significant disruptions in work, education, and social life. Treatment-resistant depression is defined as the failure to achieve improvement in depressive symptoms despite the use of at least two different antidepressant medications at adequate doses and durations. Current pharmacological approaches are inadequate for about half of treatment-resistant depression patients, and the effects of these medications on cognitive impairments are limited. Therefore, there is a need for new and effective treatment methods. This review aims to evaluate the effects of ketamine and esketamine on cognitive functions in the treatment of treatment-resistant depression patients. Relevant literature has been reviewed and recent studies have been evaluated. The results of randomized controlled trials indicate that ketamine is effective in treating treatment-resistant depression and can improve specific cognitive domains. Significant improvements in cognitive functions such as visual memory, processing speed, working memory, and attention have been recorded in patients responding to 0.5 mg/kg ketamine infusion. However, long-term use of ketamine may have negative effects on spatial working memory. Esketamine, an NMDA receptor antagonist, has shown rapid and effective antidepressant outcomes, providing stability or improvement in cognitive functions. Additionally, its intranasal administration offers practical advantages. However, findings suggest that high doses of esketamine may have neurotoxic effects and negatively impact cognitive functions. The effects of both drugs on depressive symptoms and cognitive functions vary depending on dose, duration of use, and frequency of administration. In conclusion, while ketamine and esketamine show significant potential in the treatment of treatment-resistant depression and improvement of cognitive symptoms, further research is needed regarding their long-term effects and safety.

Anahtar Kelimeler

Treatment-Resistant Depression, Ketamine, Esketamine, Cognitive Functions

Kaynakça

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