• Roger Chou, P Todd Korthuis, Dennis McCarty, Phillip O Coffin, Jessica C Griffin, Cynthia Davis-O'Reilly, Sara Grusing, and Mohamud Daya.
• From Oregon Health & Science University, Portland, Oregon, and San Francisco Department of Public Health, San Francisco, California.
• Ann. Intern. Med. 2017 Dec 19; 167 (12): 867-875.

BackgroundNaloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain.PurposeTo synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone.Data SourcesOvid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists.Study SelectionEnglish-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms.Data ExtractionDual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE).Data SynthesisOf 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment.LimitationThere were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations.ConclusionHigher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport.Primary Funding SourceAgency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).

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