Insomnia is the most prevalent sleep disorder, estimated to affect at least one-third of the global population. There are a variety of treatment options available for both acute and chronic insomnia. Currently, the pharmacological arsenal for treating insomnia includes short- or intermediate-acting benzodiazepine hypnotics, non-benzodiazepine hypnotic sedatives, melatonin receptor agonists, orexin receptor antagonist, and sedating antidepressants. Diphenhydramine, a first-generation antihistamine, is commonly used in the treatment of allergies and dermatitis. This review examines the preclinical and clinical efficacy and safety evidence of diphenhydramine in treating short-term insomnia. Additionally, it provides expert consensus on its implementation as an over-the-counter medication for this condition. The available evidence indicates that diphenhydramine is an effective treatment for acute insomnia in adults, offering a safe and affordable option for most patients suffering from this condition. Experts concur that there is strong evidence supporting the recommendation of diphenhydramine for the treatment of acute insomnia in adults.
