Diphenhydramine

Nervous system

Diphenhydramine can cause significant daytime neurological impairment comparable to intoxication with alcohol [ ]. In a study of injury rates in 12 106 patients taking diphenhydramine compared with 24 968 patients taking loratadine, using a health-care claims database that included employees, dependents, and retirees who filed claims from January 1991 to December 1998, there was a strong association between the use of diphenhydramine and the occurrence of injuries: 55% of all injuries were associated with its use. The loratadine and diphenhydramine groups had similar predrug intake injury rates. The authors concluded that a substantial number of excess injuries and costs had been incurred as the result of the use of diphenhydramine [ ].

Neuroleptic malignant syndrome has been attributed to diphenhydramine [ ].

• A 39-year-old man presented with a gait disturbance confusion, hyperthermia (38.2 °C), and hyperhidrosis after massive ingestion of a formulation containing diphenhydramine. With intensive support, including bromocriptine, he recovered within 12 days. The estimated dose of diphenhydramine was 40 mg × 60 tablets, and each tablet included 26 mg of diprophylline, a xanthine derivative.

The genesis of this case was not clear. Atropine-like effects occur with diphenhydramine, although signs such as muscle rigidity, akinesia, and hyperhidrosis, cannot be ascribed to anticholinergic activity. However, the patient had also taken sulpiride, which is a potent dopamine receptor antagonist.

Diphenhydramine can cause extrapyramidal symptoms as part of an acute dystonic reaction [ ].

Psychological

Use of diphenhydramine, mainly as a sleeping aid, has been associated with cognitive impairment in elderly people without dementia [ ].

Psychiatric

Diphenhydramine has been associated with acute delirium in elderly patients with mild dementia, even in single doses of 25 mg [ ].

Children and adolescents who are given diphenhydramine as premedication, often intravenously as a bolus, to prevent the adverse effects of blood transfusion, can develop drug-seeking behavior. It is recommended that in these circumstances antihistamines should be given orally or infused slowly [ ].