Case Study | Discontinuing Long-Term Opioid Therapy for Chronic Pain Through a Biopsychosocial Lens

A 61-year-old woman with lifelong chronic pain developed new psychosis during months of recurrent opioid withdrawal while self-treating with diphenhydramine. Initial workup was normal. We review the differential, why late-life first-episode psychosis is a red flag, and the role of antihistamines and opioid withdrawal in confusion versus persistent psychosis. Treatment used a biopsychosocial plan: rotate antipsychotic to olanzapine with careful titration, optimize SSRI, stop diphenhydramine, transition short-acting oxycodone to extended-release morphine then taper off, start duloxetine and diclofenac, add PT, CBT, and nicotine replacement. At 12 months she was euthymic, off opioids, and socially active. We discuss possible mechanisms including kappa receptor effects and dopamine pathways.