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Antidepressants/donepezil/valproate-semisodium Serotonin syndrome: case report

A 74-year-old man developed serotonin syndrome (SS) during treatment with quetiapine, valproate-semisodium, venlafaxine, trazodone and donepezil for agitation, mood swings, migraine prophylaxis, depression or aggression [routes not stated]. The man presented with generalised shaking, tremors, clonus, and altered level of consciousness on 12 February 2018. Nine hours before presentation, he was normal. His medical history was significant for type II diabetes mellitus and traumatic brain injury (TBI), with a subdural frontal and temporal intracranial haemorrhage after falling from a ladder 3 years ago. His medical history was unremarkable for a seizure disorder. He was admitted. At the time of admission, his home medications included quetiapine 25mg twice/day for aggression, valproate-semisodium [divalproex sodium] 125mg twice daily for mood swings and migraine prophylaxis, venlafaxine 37.5mg twice/day for persistent depressive symptoms and migraine prophylaxis, trazodone 50mg as needed (taken 2–3 times/week) for depression and donepezil 10 mg once/day for agitation and aggression, amongst other medications. He had been initiated on quetiapine and trazodone 3 years ago, after TBI, whereas venlafaxine and valproate-semisodium were initiated in July 2016 and May 2016, respectively. Two months before presentation, valproate-semisodium had been increased to 250mg twice/day. Upon admission, he had a fever, HR was 120 beats/minute, BP was 188/84mm Hg and respiration rate was 23. Laboratory investigation showed increased creatinine kinase and hypocalcaemia. On clinical evaluation, he showed tremors, 3+ hyperreflexia in lower limbs, altered mental status and a Glasgow Coma Scale of 3. He was intubated and shifted to ICU. His hyperthermia did not respond to unspecified antipyretics or cooling blankets. After laboratory, diagnostic and microbiological assessment the aetiology of encephalopathy-hepatic, endocrine, metabolic, Wernicke’s, seizures were ruled out. Because of insignificant CSF evaluation, the differential diagnosis of viral and bacterial encephalopathy remained. Due to a negative EEG and a lack of tonic or clonic activity, a low level of suspicion for seizures remained. A diagnosis of SS was considered likely based on his symptoms and home medication list that included valproate-semisodium, donepezil, venlafaxine and trazodone. Therefore, the man was treated with cyproheptadine and midazolam for SS. Additionally, quetiapine, valproate-semisodium, donepezil, trazodone, memantine, venlafaxine, and melatonin were held. On day 3, he regained normal neurological and muscular functioning. He was extubated, and cyproheptadine was stopped after a total of 50 hours of therapy. After a psychiatric consultation, trazodone and venlafaxine were permanently discontinued. On 21 February 2018, he was discharged and quetiapine 25mg twice daily was re-initiated for aggression, as were mirtazapine and memantine. At a follow-up after 2 months of hospi