What is the treatment for diphenhydramine (Benadryl) abuse?

Treatment of Diphenhydramine (Benadryl) Abuse

For diphenhydramine abuse, immediately discontinue the drug and initiate a gradual dose reduction protocol under medical supervision, combined with treatment of any acute toxicity using supportive care, benzodiazepines for agitation/seizures, and sodium bicarbonate for cardiac conduction abnormalities. 1, 2, 3

Immediate Assessment and Stabilization

Initial Management

• Stop all diphenhydramine administration immediately and assess airway, breathing, and circulation 1
• Establish intravenous access and administer supplemental oxygen as needed 1
• Monitor vital signs continuously, particularly cardiac rhythm for QRS prolongation and dysrhythmias 1
• Obtain detailed history including daily dose consumed, duration of abuse, and presence of co-ingestants 2

Emergency Department Referral Criteria

• All patients with suicidal intent, intentional abuse, or suspected malicious intent require emergency department evaluation 2
• Refer patients experiencing moderate to severe symptoms including agitation, hallucinations, abnormal muscle movements, loss of consciousness, seizures, or respiratory depression 2
• Children under 6 years who ingested ≥7.5 mg/kg or patients ≥6 years who ingested ≥7.5 mg/kg or 300 mg (whichever is less) require emergency evaluation 2

Management of Acute Toxicity

Cardiovascular Complications

• For QRS prolongation >0.10 msec or wide-complex dysrhythmias, administer sodium bicarbonate 1-2 mEq/kg IV bolus 1, 2
• Diphenhydramine acts as a sodium channel blocker causing cardiac toxicity similar to tricyclic antidepressants 1
• For hypotension unresponsive to IV fluid resuscitation, administer vasopressors such as dopamine or vasopressin 1

Neurological Complications

• Administer benzodiazepines for seizures or severe agitation 1, 2
• Avoid neuromuscular blockers metabolized by cholinesterase in patients with anticholinergic toxicity 1
• Physostigmine should be reserved for hospital administration only and not given in out-of-hospital settings 2

Supportive Care

• Administer IV fluids for volume resuscitation 1
• Do not induce emesis due to risk of rapid loss of consciousness or seizures 2
• Do not administer activated charcoal en route to emergency department due to aspiration risk 2

Detoxification Protocol for Chronic Abuse

Gradual Dose Reduction

• Implement a gradual dose reduction schedule rather than abrupt cessation 3
• The case literature demonstrates successful detoxification using slow taper in a patient consuming thirty 50 mg tablets daily (1500 mg/day) 3
• Inpatient detoxification may be necessary for patients with severe dependence or those using extremely high doses 3

Monitoring During Detoxification

• Monitor for withdrawal symptoms and anticholinergic rebound effects 3
• Assess for underlying psychiatric conditions, particularly psychotic illness, as there is an apparent link between antipsychotic usage and diphenhydramine abuse 3
• Follow-up at regular intervals, with documented success at 6-month follow-up in case reports 3

Special Populations and Considerations

Patients on Antipsychotics

• Be particularly vigilant for diphenhydramine abuse in patients with psychotic illness, as all reported abuse cases showed links to antipsychotic usage 3
• Patients may report using diphenhydramine to feel "good and calm" or to stop tremors from antipsychotic medications 3

Elderly Patients

• Elderly patients require reduced doses due to increased sensitivity to anticholinergic effects and higher risk of cognitive impairment, delirium, and falls 4
• Monitor closely for changes in mental status, excessive sedation, urinary retention, and constipation 4

Common Pitfalls to Avoid

• Do not assume diphenhydramine is innocuous - it has significant abuse potential and can cause fatal outcomes in overdose, with documented deaths from doses as low as 7.5 g 5, 6
• Do not overlook non-prescribed medication use when taking drug histories - specifically inquire about over-the-counter antihistamine use 3
• Community pharmacists and primary care providers should be vigilant to excessive requests for diphenhydramine, particularly in patients with chronic illnesses or psychiatric conditions 3, 6
• Avoid using diphenhydramine for ongoing treatment given the availability of safer second-generation antihistamines with fewer side effects and lower abuse potential 7