What is the treatment for reversal of amphetamine effects?

From the Guidelines

The primary treatment for reversal of amphetamine effects involves the use of benzodiazepines, such as diazepam or lorazepam, to manage symptoms like agitation, hypertension, and tachycardia, as recommended by the most recent guidelines 1. The treatment approach is focused on supportive care and targeted medications to counteract the effects of amphetamines on the body.

• Benzodiazepines are considered first-line treatment due to their effectiveness in reducing sympathetic hyperactivity, as noted in the 2019 esc council on hypertension position document 1.
• For severe hypertension, antihypertensives like phentolamine, nicardipine, or nitroprusside can be considered, as they have been shown to be effective in managing blood pressure in patients with autonomic hyper-reactivity due to amphetamine intoxication 1.
• It is crucial to avoid using pure beta-blockers, as they can worsen hypertension through unopposed alpha effects, a consideration highlighted in the management of hypertensive emergencies 1.
• Additional measures, such as physical cooling for hyperthermia, administration of activated charcoal if ingestion is recent, and IV fluids for dehydration, are also important components of the treatment regimen.
• The treatment should be continued until the patient's vital signs normalize and psychiatric symptoms resolve, which typically occurs within 24-48 hours, depending on the type and amount of amphetamine consumed.
• The approach is designed to counteract amphetamine's effects on neurotransmitters like dopamine, norepinephrine, and serotonin, which cause sympathetic overstimulation, as understood from the pathophysiology of amphetamine intoxication 1.

From the FDA Drug Label

Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states. Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated charcoal, administration of a cathartic, and sedation. Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

The treatment for reversal of amphetamine effects includes:

• Symptomatic management: gastric lavage, administration of activated charcoal, administration of a cathartic, and sedation
• Chlorpromazine: can be used to antagonize the central stimulant effects of amphetamines
• Sedation: to achieve a gradual drop in blood pressure in cases of acute, severe hypertension 2

From the Research

Reversal of Amphetamine Effects

The treatment for reversal of amphetamine effects involves various pharmacologic interventions.

• Antipsychotics and benzodiazepines are used for control of agitation and psychosis, as supported by high-quality studies 3.
• β-blockers are recommended for control of hypertension and tachycardia associated with amphetamine use, with 9 high-quality studies reporting their overall safety and efficacy 3.
• Calcium channel blockers and α-blockers have also been studied, although the evidence is limited 3.

Treatment for Amphetamine Withdrawal

There is limited evidence for the treatment of amphetamine withdrawal.

• Amineptine has been shown to reduce discontinuation rates and improve overall clinical presentation, but it is not available for use due to concerns over abuse liability 4.
• Mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal, but its benefits are less clear 4.
• Other medications, such as bupropion and naltrexone, have potential efficacy for methamphetamine withdrawal, as noted in a review of clinical research 5.

Management of Psychostimulant Withdrawal

The clinical management of psychostimulant withdrawal involves biomedical and behavioral treatments.

• Medications such as mirtazapine, naltrexone, and bupropion may be effective for methamphetamine withdrawal 5.
• Repetitive transcranial magnetic stimulation may also be effective during acute, early protracted, and late protracted withdrawal phases 5.
• Topiramate shows mixed evidence of efficacy for cocaine withdrawal 5.

Note: The evidence for the treatment of amphetamine reversal and withdrawal is limited, and further research is needed to evaluate new agents and define treatment for these patients 3, 4, 5.