Neurotoxicity and nephrotoxicity caused by combined use of lithium and risperidone: a case report and literature review

Abstract

BackgroundCombination lithium, a mood stabilizer, and risperidone, an atypical antipsychotic drug, is widely used for treatment of psychotic disorders. Rare reports concern severe adverse drug reaction in multiple organic systems with their combined use. We report two episodes of neurotoxicity and nephrotoxicity in a patient following the combined use of lithium and risperidone.Case presentationA 55-year-old male had a diagnosis of schizoaffective disorder at the age of 51. He was initially treated with a combination of lithium and olanzapine 5 to 15 mg/day for 2 years. He was admitted to psychiatric ward at the age of 53 due to manic episode with psychotic feature. Because of poor blood sugar control, we switched olanzapine 20 mg/day to risperidone 4.5 mg/day with combination of lithium 900mg/day. The patient presented neurotoxicity, neuroleptic-malignant-syndrome like symptoms, and nephrotoxicity, elevation of blood creatinine and decreased urine output few days later. These signs were fully recovered within 2 days after we discontinued all medications and gave normal saline hydration. Then we re-administered decreased dosage of lithium 600 mg/day and risperidone 3 mg/day, and the similar episode occurred again 3 days later. All drugs were discontinued again, then his delirium resolved and abnormal data returned to normal 1 day later. Finally, the patient was treated with risperidone 2 mg/day as monotherapy, and no episode of neurotoxicity and nephrotoxicity appeared in the following 2 years.ConclusionsThe case exemplifies neurotoxicity and nephrotoxicity after combined use of lithium and risperidone. These adverse effects resolved soon after discontinuing these medications and adequate hydration. Clinicians should be cautious about neurological and renal adverse effects.

Olanzapine-induced renal damage and metabolic side effects: the protective effect of thymoquinone

“…Cr and BUN were the classical standards to evaluate renal damage (34). Accordingly, Hsu et al demonstrated the observation of elevated Cr in an atypical antipsychotic drug administration (35). The current study demonstrates that OLZ exposure produced a significant increase in the levels of Cr and BUN indicating damaged structural and functional kidney integrity.…”

The toxic effects of lithium combined with quetiapine and risperidone on organ systems

“…Lityum, risperidon ve ketiapin dopamin nörotransmisyonunun bileşenlerini modüle etmektedirler (9,10,13). Lityum presinaptik dopamin salınımını önleyerek, risperidon ve ketiapin ise dopamin reseptörlerini bloke ederek etki gösterirler (8,13). Lityum ve risperidon arasındaki ilaç etkileşiminden kaynaklanan nörotoksisitenin iki hipotezi vardır.…”

“…Birincisi risperidondan bağımsız sadece lityum intoksikasyonuna bağlı nörotoksisitedir. İkincisi ise, hem lityum hem de risperidonun dopamin reseptör blokajını arttırarak nörotoksisiteye yol açmasıdır (8,13). Risperidonu diğer antipsikotik ilaçlarla karşılaştıracak olursak, lityumla kombinasyonunda nörotoksik semptomların gelişme riskinin daha yüksek olduğu belirtilmektedir (13).…”

“…Lityuma bağlı nefrotoksik etkiler sonucunda da akut böbrek yetmezliği, nefrojenik diabetes insipidus, renal interstisyel fibrozis, tubular atrofi, glomeruler skleroz ve sonuçta kronik böbrek yetmezliğine kadar giden durumlar oluşabilir (3,7,13). Lityum ve antipsikotik ilaçlar arasındaki farmakodinamik etkileşimler sonucunda lityum toksisitesindeki artışın böbrekleri etkileyebileceği belirtilmekle beraber, antipsikotik ilaç kullanımının da akut böbrek hasarı riskini artırdığına dair yayınlar da vardır (3,8). Son yıllarda yayınlanan bipolar bozukluk tedavisi ile ilgili kanıta dayalı klavuzlarda, uzun yıllar kullanılan lityumun böbrekler üzerindeki advers etkilerinin bilinmesi nedeniyle, özellikle risperidon ve ketiapin gibi antipsikotikler ile kombine lityum kullanımında bu konuya özel dikkat edilmesi önerilmektedir (9).…”

“…Risperidon ve lityum kombinasyonu bipolar bozuklukta sıklıkla kullanılmasına rağmen, az sayıda birlikte kullanıma bağlı şiddetli advers ilaç reaksiyonu bildirimi vardır (8…”