Diphenhydramine as an Analgesic Adjuvant in Refractory Cancer Pain

Clinical and animal data suggest that antihistamines may have efficacy in the management of pain. While many mechanisms of action have been proposed for the analgesic action of antihistamines, the exact mechanism is unknown. Controlled clinical trials in different pain models have demonstrated that antihistamines have direct and adjuvant analgesic activity. We report three patients with advanced cancer pain refractory to adjuvants and oral, intravenous, and epidural opioids, who achieved sustained pain relief after the repeated administration of diphenhydramine. Diphenhydramine may be useful in the treatment of neuropathic and nociceptive pain that has failed to respond to treatment with opioids and adjuvant analgesics. We suggest a starting dose of 25 mg of oral or parenteral diphenhydramine every 6 to 8 hours, with titration to effect.