Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review.
BACKGROUND
Overdose of amphetamine, related derivatives, and analogues (ARDA) continues to be a serious worldwide health problem. Patients frequently present to the hospital and require treatment for agitation, psychosis, and hyperadrenegic symptoms leading to pathologic sequelae and mortality.


OBJECTIVE
To review the pharmacologic treatment of agitation, psychosis, and the hyperadrenergic state resulting from ARDA toxicity.


METHODS
MEDLINE, PsycINFO, and the Cochrane Library were searched from inception to September 2014. Articles on pharmacologic treatment of ARDA-induced agitation, psychosis, and hyperadrenergic symptoms were selected. Evidence was graded using Oxford CEBM. Treatment recommendations were compared to current ACCF/AHA guidelines.


RESULTS
The search resulted in 6082 articles with 81 eligible treatment involving 835 human subjects. There were 6 high-quality studies supporting the use of antipsychotics and benzodiazepines for control of agitation and psychosis. There were several case reports detailing the successful use of dexmedetomidine for this indication. There were 9 high-quality studies reporting the overall safety and efficacy of β-blockers for control of hypertension and tachycardia associated with ARDA. There were 3 high-quality studies of calcium channel blockers. There were 2 level I studies of α-blockers and a small number of case reports for nitric oxide-mediated vasodilators.


CONCLUSIONS
High-quality evidence for pharmacologic treatment of overdose from ARDA is limited but can help guide management of acute agitation, psychosis, tachycardia, and hypertension. The use of butyrophenone and later-generation antipsychotics, benzodiazepines, and β-blockers is recommended based on existing evidence. Future randomized prospective trials are needed to evaluate new agents and further define treatment of these patients.
Department of Emergency Medicine, University of California Davis Medical Center, Sacramento, CA, United States. Electronic address: jrrichards@ucdavis.edu.
John R
JR
Richards
Department of Internal Medicine, Divisions of Toxicology, Pulmonary and Critical Care, University of California Davis Medical Center, Sacramento, CA, United States; Northern California VA Medical System, Sacramento, CA, United States.
Timothy E
TE
Albertson
Department of Emergency Medicine, University of California Davis Medical Center, Sacramento, CA, United States.
Robert W
RW
Derlet
Department of Medicine, Division of Cardiology, University of Texas Health Sciences Center, San Antonio, TX, United States.
Richard A
RA
Lange
Department of Medicine, University of California, San Francisco, CA, United States; Department of Clinical Pharmacy, University of California, San Francisco, California Poison Control System, San Francisco Division, San Francisco, CA, United States.
Kent R
KR
Olson
Department of Emergency Medicine, Oregon Health Sciences University, Oregon Poison Center, Portland, OR, United States.
B Zane
BZ
Horowitz
D018674:Adrenergic Antagonists / Q000627:therapeutic use; D017109:Akathisia, Drug-Induced / Q000188:drug therapy*; D019969:Amphetamine-Related Disorders; D000662:Amphetamines / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D020927:Dexmedetomidine / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D011446:Prospective Studies; D011605:Psychoses, Substance-Induced / Q000188:drug therapy*; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy*
D018674:Adrenergic Antagonists; D000662:Amphetamines; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D020927:Dexmedetomidine
Agitation; Amphetamines; Beta-blockers; Hypertension; Sedation; Tachycardia