Klozafobik tutumlara karşı güncellenmiş klozapin ile tedavi kılavuzu

Son yıllarda klozapin ile ilgili yayınlar giderek artmaktadır. Tüm yeni kuşak antipsikotiklerin varlığına rağmen şizofreni hastalarının üçte biri hala tedaviye dirençlidir. Klozapin, yeterli dozda iki ayrı gruptan antipsikotik ile en az 6 hafta süre ile yapılan tedaviye dirençli şizofreni hastalarında altın standart ve FDA onayı almış benzersiz bir antipsikotiktir. Bunun yanı sıra, şizofreni ve şizoaffektif bozuklukta intihar davranışı riskini azaltması nedeniyle de FDA onayı almış tek antipsikotik ilaçtır. Şizofreni hastalarının en az %30'unda tedaviye direnç ve %5'inde intihar nedeniyle kayıplar söz konusu iken; klozapin dünyada ve Türkiye'de beklenenden en az 10-15 kat daha az ve %2-10 sıklıkta kullanılmaktadır. Bunun nedenini tüm fobilerde olduğu gibi rasyonel olarak açıklamak mümkün değildir. Bu tutumu tam olarak fobi ya da klozafobi olarak tanımlamak mümkün değilse de en azından 'klozafobik bir tutum' olarak nitelendirmek doğru olabilir. Kanaatimizce, psikiyatri uzmanlarının klozafobik tutumları nedeniyle klozapini gereğinden çok az oranlarda kullanmaları, tüm dünyada olduğu gibi Türkiye'de de önemli bir halk sağlığı sorunudur dersek abartmış olmayız. Bu durumun klozafobik tutumdan başka en belli başlı nedeni reçete yazan klinisyenlerin ciddi yan etkileri yönetmede yeterli bilinç ve tecrübeden yoksun olmalarıdır. Klozapin; agranülositoz, miyokardit/ kardiyomiyopati ve epileptik nöbetler gibi ciddi ters etkiler yanı sıra, kilo alımı, metabolik sendrom ve konstipasyon gibi ihmal edildiğinde tehlikeli diğer yan etkilere sebep olabilmektedir. Ayrıca, gündüzleri sedasyon ile geceleyin idrar kaçırma ve hipersalivasyon gibi yan etkiler hastaların yaşam kalitesini olumsuz yönde etkileyebilmektedir. 18 hafta boyunca her hafta kan sayımı yapılması gerekliliği hekimlerin klozapini kullanmaları konusunda isteksiz olmalarına yol açmaktadır. Bu yan etkiler ve zorluklar aslında bilinçli yaklaşımlarla aşılabilir. FDA'nin REMS (Risk Değerlendirme ve Azaltma Stratejisi) programı, klinisyenleri klozapin kullanımı konusunda yüreklendirmektedir. Bu gözden geçirme makalesinde klozafobiyi yenmek için güncel bilgiler verilmiş ve de ortaya çıkabilecek yan etkiler için gerekli önlemler alınarak bunların üstesinden gelinebileceği ve yönetilebilecekleri anlatılmaya çalışılarak, klinisyenlerin bu çok değerli ve farmakoekonomik yönden diğer antipsikotiklerden daha avantajlı antipsikotik ilaç konusunda bilgilendirilmeleri amaçlanmıştır.

An updated clozapine treatment guide against clozaphobic attitudes

In recent years, clozapine-related publications are gradually increasing. Despite all the new generation of antipsychotics, one-third of patients with scizophrenia are still treatment-resistant. Clozapine is a unique and gold standard antipsychotics with FDA approval for treatment-resistant schizophrenia cases following failure with antipsyhotics from two separate groups with sufficient doses for at least six weeks duration and also preventing suicidal behavior in patients with schizophrenia and schizoaffective disorder. While at least 30% of schizophrenia patients are treatment- resistant and suicide rate is 5%; clozapine, both in Turkey and around the world, is used 10-15 times less in 2-10% of patients. This is not easy to explain rationally like in phobias. Although this cannot be exactly labeled as phobia or clozaphobia, labeling it as a clozaphobic attitude might be appropriate. In our opinion, claiming that prescription of clozapine less than required by the psychiatrists in Turkey due to this clozaphobic attitude is an important public health problem would not be an exaggeration. In addition to clozaphobic attitude, one of the major reasons underlying this attitude is clinicians' lack of adequate awareness and experience in managing the potential serious adverse events. Clozapine causes major adverse events such as agranulocytosis, myocarditis/ cardiomyopathy, and epileptic seizures along with side effects such as weight gain, constipation, metabolic syndrome which might compromise patient's health. In addition, daytime sedation, urinary incontinence at night, and hipersalivation can adveresly affect the quality of life of patients. Blood count monitoring for 18 weeks is another reason for reluctant use of clozapine. All these side effects and challenges can be overcome with specific approaches. The FDA promoted a rational use of clozapine with REMS (Risk Evaluation and Mitigation Strategy) program. In this review, updated information about clozapine have been outlined and clinicians were aimed to be informed by the pharmacoeconomics advantages of clozapine and how to overcome the potential adverse events in clozapine use

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