Table 1.

Comparative studies of IN and parenteral naloxone formulations in patients

Reference	Study design	n and population	IN dose and formulation	Dose comparator	Summary of key findings
Loimer et al34	Randomized trial	17 patients (7 IV vs IM; 10 IV vs IN)	1 mg (1 mg/0.4 mL)	1 mg IM	Both IN and IM groups showed significant withdrawal symptoms at 15 and 45 min. Only the IN group exhibited withdrawal symptoms at 5 min, suggesting more rapid onset with IN administration
Loimer et al35	Controlled, nonrandomized, prospective trial	30 patients (22 opioid dependent, 8 control)	1 mg (1 mg/0.4 mL)	None	After opioid challenge test of IN naloxone administration, opiate-dependent patients showed significantly higher ratings on a withdrawal scale for up to 30 min (in comparison to controls)
Kelly and Koutsogiannis37	Case report	Six patients	0.8–2 mg	None	For all patients, return of adequate spontaneous respiration occurred with a median of 50 s (range: 30 s–2 min)
Barton et al38	Case series	30 patients	2 mg (1 mg/mL)	2 mg IV if no response	11 patients responded to naloxone challenge (IN or IV), of whom 10 (91%) responded to IN alone, with an average response time of 3.4 min
Barton et al39	Case series	95 patients	2 mg (1 mg/mL)	2 mg IV if no response	52 patients responded to naloxone challenge (IN or IV), of whom 43 (83%) responded to IN alone, with an average response time of 4.2 min
Kelly et al40	Randomized trial	155 patients (71 IM, 84 IN)	2 mg/5 mL	2 mg IM	The IM group had more rapid respiratory response (6 min) than the IN group (8 min), but no significant difference in GCS scores or need for rescue naloxone (13% IM vs 26% IN)
Kerr et al41	Randomized trial	172 patients (89 IM, 83 IN)	2 mg (2 mg/mL; 0.5 mL/nostril)	2 mg IM	The rates of response within 10 min were similar: IN naloxone (60/83, 72.3%) compared with IM naloxone (69/89, 77.5%). No group difference in mean response time (IN: 8.0, IM: 7.9 min) Significant group difference in need for rescue naloxone: IN 18% vs IM 5%
Doe-Simkinset al45	Pre–post comparison	385 opioid users	2 mg 2 mg/2 mL)	None	Participants reported 74 successful OD reversals; no deaths
Robertson et al43	Retrospectivechart review	154 patients (50 IN, 104 IV)	2 mg (1 mg/nostril)	1 mg IV	Although the time from dose administration to clinical response (increase in RR or GCS >6 points) took significantly longer for IN than IV patients (12.9 vs 8.1 min), the overall time from patient contact to response was the same (~20 min). Ninety-four percent of IN patients did not require supplemental naloxone by IV or IM administration
Merlin et al44	Retrospective chart review	93 (38 IN, 55 IM; subsample of 344 cases)	2 mg (1 mg/nostril)	IV naloxone titrated to effect: 2 mg average	No group difference in RR or GCS pre-naloxone administration. Post-naloxone administration, both the median RR and GCS scores were significantly higher for the IV group than the IN group; nine IN patients (23%) required rescue IV naloxone
Weber et al11	Retrospective chart review	105 patients	2 mg (2 mg/3 mL)	None	Of all 105 cases, 23 (22%) had complete response, 62 (59%) had partial response, and 20 (19%) showed no response, as indicated by GCS score and RR. Eleven cases (10%) received rescue naloxone (6 IV, 5 IM). No adverse events or deaths occurred
Walley et al46	Interrupted time-series analysis	2,912 opioid users	2 mg (2 mg/2 mL)	Communities without take- home naloxone	Participants reported 327 successful OD reversals; no deaths OD mortality rates were reduced in 19 communities with THN, compared to those without THN
Walley et al47	Pre–post comparison	1,553 methadone clients	2 mg (2 mg/2 mL)	None	Methadone clients reported 92 successful OD reversals; no deaths
Sabzghabaee et al42	Randomized trial	100 patients (50 IN, 50 IV)	0.4 mg (0.4 mg/2 mL; 1 mL/nostril)	0.4 mg IV	Although patients responded about 1 min sooner to IV compared to IN naloxone, the level of consciousness was higher in patients administered IN naloxone (0% obtunded or lower) than those in the IV group (40% obtunded). Post-naloxone agitation occurred in 25% of IV patients and 0% of IN patients

Notes: The table is updated and modified from tables of studies compiled in previous reviews;16,19,25 summaries of the listed studies differ from those previously provided in several cases, as deemed appropriate based on clinical as well as statistical significance.

Abbreviations: GCS, Glasgow Coma Scale; IM, intramuscular; IN, intranasal; IV, intravenous; OD, overdose; RR, respiratory rate; THN, take-home naloxone.