Eren YILDIZHAN, Nesrin Buket TOMRUK, Armağan ÖZDEMİR, Mehmetcan KAÇAR, YASEMİN ÇELİK ALTUNOĞLU, Doğan YILMAZ, Cenk VARLİK

Role of valproate in hyperammonemic encephalopathy in women in a tertiary psychiatric clinic

Objective: In patients with acute mental status change with elevated serum ammonia levels, when there is conco- mitant use of valproate, carbamazepine or any other susceptible agent, hyperammonemic encephalopathy is a possible phenomenon. Our aim was to describe this underreported phenomenon in detail and find possible risk factors associated with valproate induced hyperammonemic encephalopathy. Methods: We analyzed retrospective records of two years for female inpatients in the psychiatric ward for women in our hospital. Spearman’s rho correlation analysis was used for assessing the relation between serum ammonia and valproate levels. During the two years’ period, 961 patients were treated in the inpatient clinic. Because of a suspicion of hyperammonemic encephalopathy, serum ammonia levels of 37 patients were analyzed, revealing a total of 34 patients with high ammonia levels, warranting a diagnosis of hyperammonemic encephalopathy. Results: In 28 of these patients hyperammonemic encephalopathy was associated with valproate use. The time interval between initiation of valproate treatment and hyperammonemia was 11±7 days. For these patients, initiation dose of valproate was 883.93±249.83 mg/day (median: 1000 mg/day), daily valproate dose was 914.90±202.87 (median: 928.25) mg and during encephalopathy; valproate blood level was 82.36±25.80 ng/mL (median: 87.50 ng/mL). Serum ammonia level was positively correlated with initiation dose of valproate ( ρ (28) =0.472, p=0.011) and valproate blood levels during hyperammonemia ( ρ (28) =0.522, p=0.004). Polypharmacy and long-term intramuscular treatment were also prevalent in patients with hyperammonemic encephalopathy. Discussion: Early suspicion of hyperammonemic encephalopathy in patients taking valproate may improve the outcome of this under recognized problem. (Ana- tolian Journal of Psychiatry 2019; 20(6):589-596)

Bir üçüncü basamak psikiyatri servisindeki kadınlarda hiperamonyemik ensefalopatide valproik asidin rolü

Amaç: Akut mental durum değişikliği olan hastalarda yüksek serum amonyak değeri ve valproik asit, karbamazepin veya diğer etken ajanlardan birinin kullanımı varsa, hiperamonyemik ensefalopati olası bir durumdur. Literatürde nadir bildirilmiş olan bu durumu ayrıntılı olarak tanımlamayı ve valproik asite bağlı hiperamonyemik ensefalopati riskini artıran etkenleri araştırmayı amaçladık. Yöntem: Geriye dönük olarak, hastanemizdeki kadınlar için yataklı psikiyatri servisinde tedavi görmüş olan hastaların iki yıllık kayıtlarını inceledik. Serum amonyak düzeyleri ve val- proik asit düzeyleri arasındaki ilişkiyi Spearman’s rho korelasyon analizi ile inceledik. İki yıllık dönemde, yatan hasta servisinde 961 hasta tedavi edilmişti. Otuz yedi hastada hiperamonyemik ensefalopati şüphesi ile serum amonyak düzeyi tetkik edilmiş ve 34 hastada amonyak düzeyleri yüksek saptanarak hiperamonyemik ensefalopati tanısı konmuştu. Sonuçlar: Yirmi sekiz hastada hiperamonyemik ensefalopati valproik asit kullanımı ile ilişkiliydi. Valproik asitin başlanması ve hiperamonyemi arasındaki süre 11±7 gündü. Bu hastalarda valproik asit başlangıç dozu 883,93±249,83 mg/gün (medyan: 1000mg/gün), günlük valproik asit dozu 914.90±202.87 mg (medyan: 928.25 mg) ve ensefalopati sırasında valproik asit kan düzeyi 82.36±25.80 ng/mL (medyan: 87.50 ng/mL) saptandı. Serum amonyak düzeyleri, valproik asit başlangıç dozu ( ρ (28) =0.472, p=0.011) ve valproik asit kan düzeyleri ile ( ρ (28) =0.522, p=0.004) pozitif korelasyon göstermekteydi. Hiperamonyemik ensefalopatisi olan hastalarda çoklu ilaç kullanımı ve uzun süreli intramusküler antipsikotik kullanımının da sık olduğu görüldü. Tartışma: Valproik asit kullanan hasta- larda hiperamonyemik ensefalopatiden erken akla gelmesi, farkındalığın az olduğu bu sorun ile ilgili klinik sonuçların daha olumlu olmasını sağlayabilir. (Anadolu Psikiyatri Derg 2019; 20(6):589-596)

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