What is the role of quetiapine (Seroquel) in managing a methamphetamine (meth) overdose?

Quetiapine for Methamphetamine Overdose

Quetiapine has no role in the acute management of methamphetamine overdose—benzodiazepines are the first-line treatment for agitation, hypertension, and tachycardia, with nitroglycerin or calcium channel blockers added for cardiovascular complications. 1, 2

First-Line Management of Acute Methamphetamine Overdose

Benzodiazepines are the cornerstone of treatment for methamphetamine overdose, addressing both central nervous system hyperactivity and peripheral sympathomimetic effects (agitation, hypertension, tachycardia, psychosis). 1, 2

Cardiovascular Complications

• Administer sublingual nitroglycerin or intravenous calcium channel blockers (e.g., diltiazem 20 mg IV) as first-line therapy for chest pain with suspected coronary vasospasm. 2
• Strictly avoid beta-blockers (including labetalol) in acute methamphetamine intoxication, as they worsen coronary vasospasm through unopposed alpha-adrenergic stimulation. 1, 2
• Benzodiazepines combined with nitroglycerin provide superior control of hypertension and tachycardia compared to other agents. 1, 2

Monitoring Requirements

• Obtain immediate 12-lead ECG to evaluate for ST-elevation, ischemia, or arrhythmias. 2
• Check cardiac biomarkers (troponin) to assess for myocardial injury, as methamphetamine causes true acute coronary syndromes through vasospasm, thrombosis, and plaque rupture even in patients with normal coronary arteries. 2
• Observe patients with ECG changes and normal biomarkers for 9-24 hours in a monitored setting, as most complications occur within this timeframe. 2

Role of Antipsychotics in Methamphetamine Toxicity

When Antipsychotics May Be Considered

Quetiapine has been studied for methamphetamine-induced psychosis (not acute overdose), showing comparable efficacy to haloperidol in a randomized controlled trial of 80 patients treated for 4 weeks. 3 However, this evidence applies to subacute psychotic symptoms after intoxication resolves, not acute overdose management.

Why Quetiapine Is Not Used Acutely

• Benzodiazepines work faster and address the underlying sympathomimetic toxidrome more effectively than antipsychotics. 1, 2
• Quetiapine's long half-life prevents immediate correction if hypotension develops. 1
• No guideline recommends antipsychotics as first-line treatment for acute methamphetamine overdose. 1, 2
• Antipsychotics may be used in inpatient withdrawal protocols for behavior-targeted management, but only after acute intoxication is controlled. 4

Critical Pitfalls to Avoid

• Never use beta-blockers (including combined alpha-beta blockers like labetalol) in acute methamphetamine intoxication—they precipitate worse outcomes by allowing unopposed alpha-adrenergic vasoconstriction. 1, 2
• Do not delay benzodiazepines while waiting for antipsychotics to work—every minute at high temperatures with ongoing agitation causes irreversible organ damage from hyperthermia and rhabdomyolysis. 2
• Recognize that ST-elevation can represent true STEMI, not just vasospasm—immediate angiography is indicated if ST-elevation persists despite nitroglycerin and calcium channel blockers, or if cardiac biomarkers are positive. 2

Severe Cases Requiring Escalation

For life-threatening hyperthermia (temperature >40°C) with continued agitation despite maximal benzodiazepine sedation:

• Immediate intubation is required for airway protection and definitive management, as continued agitation indicates inability to control metabolic heat production. 2
• Paralyze and sedate with continuous benzodiazepine infusion to eliminate muscle heat production, combined with aggressive cooling measures (chilled saline bolus, external cooling). 2
• Mortality approaches 11% in severe sympathomimetic toxicity with hyperthermia, with significant morbidity from rhabdomyolysis, renal failure, seizures, and DIC. 2