Neuroleptic malignant syndrome: risk factors, pathophysiology, and treatment

Abstract

Neuroleptic malignant syndrome (NMS) is associated with the administration of antipsychotic agents and other drugs such as l-dopa, antidepressants, and antihistaminic agents. Unexpected changes in mental status, new-onset catatonia, episodic tachycardia, tachypnea, hypertension, dysarthria, dysphagia, diaphoresis, sialorrhea, incontinence, low-grade temperature elevations, and rigidity should arouse suspicion. Several lines of evidence provide support for the involvement of dopamine. Most of the drugs implicated in NMS are D2 dopamine receptor antagonists. Central noradrenergic activity is also possibly related to the disorder, as sympathetic hyperactivity is associated with the active phase of NMS. Currently, the definitive role of GABA deficiency in NMS is yet to be established. Differential diagnosis should include malignant hyperthermia, lethal catatonia, lithium toxicity, serotonin syndrome, and heat stroke. A high degree of suspicion and the discontinuation of antipsychotic agents even if the diagnosis is not established are essential for the safety of the patient. Treatment of NMS should be individualized and be based empirically on the character, duration, and severity of the clinical signs and symptoms noted. The initial step in the treatment of NMS is the removal of the offending agent. Full-blown NMS is a serious condition and requires immediate supportive, nutritive, and electrolyte therapies. The administration of drugs that can improve NMS, such as IV dantrolene and/or oral bromocriptine, may also be taken into consideration, based on the severity and nature of the NMS.

Nöroleptik malign sendrom gelişiminde demografik ve klinik risk etkenlerinin araştırılması: Literatürdeki Türkçe olguların değerlendirilmesi / Detection of demografic and clinical risk factors associated with neuroleptic malignant syndrome: evaluation of cases in the Turkish literature

“…Uluslararası literatürde de, MR varlığında NMS ortaya çıkma riskinin daha yüksek olduğu bildirilmiştir (3,30). Bizim araştırmamızda örneklemin küçük-lüğü bu durumu yorumlamayı güçleştirse de, MR hastalarında istatistiksel olarak anlamlı düzeyde daha yük-sek doz antipsikotik kullanıldığının saptanması dikkat (39,44,45). Benzer olarak çalışmamızda; rijidite, bilinç bozukluğu ve terlemenin hastaların çoğunda tabloya eşlik ettiği gözlenirken, ortalama vücut ısısı, 38.8°C olarak saptanmıştır.…”

“…Erken olgularda NMS bulguları, sadece sıvı replasmanı, elektrolit dengesizliğinin düzenlenmesi gibi destekleyici tedavi ile gerileyebilirken, daha ağır olgularda böbrek yetmezliğini önleyici destekleyici tedaviye ek olarak, IV dantrolen ve/veya bromokriptin tedaviye eklenebilir (44). Bromokriptin ve amantadin gibi dopaminerjik ajanların iyileşme süresini kısalttığı, mortaliteyi önlediği bildirilmiştir (4).…”

“…Benzodiazepinlerin katatonik özellikler gösteren orta şiddetli NMS olgularında faydalı olabileceğini bildiren çalışmaların yanı sıra, klinik etki veya katkı sağlamadığı-nı bildirenler de bulunmaktadır (6). Farmakoterapinin yetersiz kaldığı olgularda EKT de uygulanabilir (6,44). Bu araştırmada, destekleyici tedaviye ek olarak, hastaların %34.4'ü sadece bromokriptin ile tedavi edilirken, %43.9'unda ilaç kombinasyonları uygulanmıştır.…”

Neuroleptic Malignant Syndrome Secondary to Quetiapine

“…Malignant hyperthermia was ruled out, as it is most frequently associated with halogenated anesthetic agents and succinylcholine. 18 Malignant catatonia can be due to neuroleptics, but it begins with symptoms of psychotic excitement, whereas NMS exhibits as rigidity and hyperpyrexia.…”

Comments on the report of neuroleptic malignant syndrome induced by ziprasidone

“…is commonly used and is still the best known effective way of coping with such a highly lethal state as NMS in a short time period''. Although reports on the beneficial effect of benzodiazepines exist, some authors suggest that the difference between lethal catatonia and NMS exists in the response to treatment with benzodiazepines, which have proven efficacy in lethal catatonia, but not in NMS (Ananth et al 2004a). On the other hand, it is worth mentioning that the syndrome (sometimes differently called) has been reported during withdrawal of some medications, such as benzodiazepines and anticholinergics used here.…”