Chronic diphenhydramine misuse in a patient with schizophrenia mimicking neurocognitive decline: a case report

Pharming, the misuse of prescription or over-the-counter (OTC) medications for psychoactive effects, represents an emerging public health concern that may be underrecognized. Diphenhydramine (DPH), a first-generation antihistamine, is particularly susceptible to misuse due to its central anticholinergic and psychoactive properties. In patients with schizophrenia, DPH misuse may mimic or exacerbate psychiatric symptoms, complicating diagnosis and management. We present the case of a Caucasian man in his mid-60s with chronic schizophrenia and a history of cannabis and DPH misuse who presented with behavioral dysregulation, aggression, and suicidal ideation. He initially reported chronic DPH use of up to 400 mg daily and later disclosed substantially higher recent use. Clinical findings included sedation, thought disorganization, hallucinations, and impaired cognition. His course was complicated by fluctuating cognitive status and recurrent symptoms suggestive of anticholinergic toxicity during prior encounters. Long-standing cannabis use, which he described as occasional but which was repeatedly confirmed on urine drug screening, was present throughout and was regarded as an important potential confounder. During inpatient treatment and subsequent dual-diagnosis rehabilitation, DPH was discontinued, antipsychotic treatment was optimized, and structured rehabilitation was provided. Over time, psychotic symptoms, cognition, and insight improved, although recovery likely reflected multiple concurrent interventions. Diphenhydramine misuse in patients with schizophrenia may contribute to neuropsychiatric presentations, including psychotic symptoms and cognitive impairment, particularly in older adults. Recognition of OTC antihistamine misuse is important in cases of atypical or treatment-refractory symptoms. This case highlights the need for systematic assessment of nonprescribed medication use in psychiatric populations.