Can diphenhydramine (Benadryl) be used to treat occasional panic attacks in an otherwise healthy adult?

Diphenhydramine Should Not Be Used for Panic Attacks

Diphenhydramine (Benadryl) is not an appropriate treatment for panic attacks and should be avoided for this indication. There is no evidence supporting its use for panic disorder, and it carries significant risks that can worsen the clinical situation.

Why Diphenhydramine Is Inappropriate for Panic Attacks

Lack of Evidence for Panic Disorder

• No clinical trials or guidelines support diphenhydramine for panic attacks. The established first-line treatments for panic disorder are selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and cognitive behavioral therapy 1, 2, 3, 4, 5.
• Benzodiazepines (such as alprazolam or lorazepam) are the only sedative class with proven efficacy for acute panic symptoms, providing rapid relief within minutes 1, 2, 3, 5.
• Tricyclic antidepressants are also effective for panic disorder, though less well-tolerated than SSRIs 1, 3, 4, 5.

Paradoxical Reactions and Worsening Anxiety

• Diphenhydramine can cause paradoxical increases in rage and agitation, particularly unpredictable in individual patients 6.
• This paradoxical reaction could potentially worsen panic symptoms rather than alleviate them 6.
• The anticholinergic effects (confusion, delirium, restlessness) may mimic or exacerbate anxiety symptoms 7, 6, 8.

Inappropriate Mechanism of Action

• Diphenhydramine is an antihistamine with anticholinergic and sedative properties, not an anxiolytic 6, 8.
• Panic attacks involve dysregulation of serotonin, norepinephrine, and GABA neurotransmitter systems—none of which are meaningfully addressed by antihistamine blockade 1, 2, 4.
• The sedation from diphenhydramine is non-specific CNS depression, not targeted anxiety reduction 7, 6.

Evidence-Based Alternatives for Panic Attacks

For Acute Panic Attack Management

• Benzodiazepines (alprazolam, lorazepam) provide rapid relief of acute panic symptoms within minutes 1, 2, 3, 5.
• These should be reserved for short-term use or treatment-resistant cases in patients without history of dependence 4, 5.
• Benzodiazepines can be combined with SSRIs during the first weeks of treatment to provide immediate relief while waiting for antidepressant onset 5.

For Long-Term Panic Disorder Treatment

• SSRIs are the first-line treatment for panic disorder, with proven efficacy in reducing panic attack frequency and severity 1, 2, 3, 4, 5.
• SNRIs are equally effective as first-line agents 4.
• Cognitive behavioral therapy is the psychological treatment of first choice and can be used alone or combined with medication 3, 4, 5.
• Combining drug treatment with cognitive behavioral therapy is the most successful treatment strategy 4.

Critical Safety Concerns with Diphenhydramine

Guideline Recommendations Against Use

• The American Academy of Sleep Medicine explicitly recommends against using diphenhydramine even for insomnia, noting very limited efficacy (only 8 minutes reduction in sleep latency versus placebo) 7, 8, 9.
• The American Geriatrics Society recommends avoiding diphenhydramine in older adults due to 1.7-fold increased risk of delirium 7, 9.
• Multiple guidelines identify diphenhydramine as an inappropriate medication that can induce delirium and confusion 7.

Adverse Effects That Could Worsen Clinical Presentation

• Anticholinergic effects include confusion, delirium, blurred vision, dry mouth, urinary retention, tachycardia, and hypotension 7, 6, 8, 9.
• Tachycardia and hypotension from diphenhydramine could be misinterpreted as worsening panic symptoms 6, 8.
• The 4-6 hour duration of sedation may be excessive and impair function long after the panic attack has resolved 6, 8.

Common Pitfalls to Avoid

• Do not use diphenhydramine as a substitute for appropriate anxiolytic therapy. Patients may request it thinking sedation equals anxiety relief, but the mechanisms are fundamentally different 7, 6.
• Avoid the misconception that "over-the-counter equals safe for any anxiety." Diphenhydramine has significant adverse effects and no proven benefit for panic 7, 6.
• Do not delay appropriate treatment (SSRIs, cognitive behavioral therapy, or judicious benzodiazepine use) by attempting diphenhydramine first 1, 2, 3, 4, 5.