Diphenhydramine Use Disorder and Complicated Withdrawal in a Palliative Care Patient

Diphenhydramine (DPH) is an over-the-counter antihistamine medication commonly used for symptom management in palliative care. Despite the ease of access and perceived safety of DPH, there is documented evidence of potential for abuse of this medication. We present a case of a 61-year-old man with metastatic carcinoma of the distal esophagus, who was initially admitted with a pain crisis but subsequently developed a severe DPH withdrawal syndrome consisting of hyperactive delirium, autonomic dysfunction, and increased muscle tone. With careful selection of the antipsychotic agent loxapine, additional symptom management medications and scheduled tapering the patient was able to be discharged home for end-of-life care. We highlight the challenges of recognizing and managing a withdrawal syndrome in patients with terminal illnesses at end of life.