Malaria Prevention, Mefloquine Neurotoxicity, Neuropsychiatric Illness, and Risk-Benefit Analysis in the Australian Defence Force

Table 1

Summary of selected pharmacoepidemiological studies relating to mefloquine prophylaxis safety and tolerability.

Year	Reference	Country	Population	Study design	Nonsevere adverse event (AE) report	Standardised testing^1	Participants	Severe AE (%)^2	Nonsevere AE (%)^2
1993	[85]	Australia	Military	Nonrandom field trial	Unknown	Nil	40	n.d.	n.d.
1993	[78]	US	Military	RCT	Questionnaire, interview	POMS, sleep monitoring, and ESQ	203	0%	43%
1996	[75]	Australia	Civilian	Retrospective	Questionnaire (mail)	Nil	285	0%	6.3%
1996	[80]	Netherlands	Military	Nonrandom field trial	Questionnaire (mail)	Nil	2,289	0%	22.8%
1996	[83]	Switzerland	Civilian	Longitudinal	Investigator nonleading question	POMS, NES, and ESQ	420	0%	7.9%
1997	[81]	UK	Military	Nonrandom field trial	Questionnaire	Nil	317	0%	29.0%
1999	[82]	Italy	Military	Retrospective	Questionnaire	Nil	1,386	0%	17.0%
2001	[76]	Neth., Ger., UK, Can., and SA	Civilian	RCT	Questionnaire, interview	Nil	483	0%	3.9%
2002	[77]	Netherlands	Civilian	RCT	Screening, interview	POMS, NES	58	n.d.	n.d.
2005	[88]	Australia	Military	Nonrandom field trial	Questionnaire	Nil	1,157	n.d.	n.d.
2005	[91]	Canada	Military	Retrospective	Data-mining medical records	Nil	1,413	n.d.	n.d.
2007	[79]	Japan	Military	Nonrandom field trial	Questionnaire	Nil	1,876	0%	18.2%
2008	[84]	Sweden	Military	Retrospective	Questionnaire	Nil	488	0%	57%
2010	[87]	Australia	Military	Nonrandom field trial	Investigator nonleading question	Nil	162	0%	11.7%
2014	[90]	Denmark	Civilian	Retrospective	AE report to drug regulator	SCL-90-R, PSE, and SF-36 (long-term)	67^3	n/a^4	n/a^4
Total							10,664

Notes.
POMS: Profile of Mood States. ESQ: Environmental Symptoms Questionnaire. NES: Neurobehavioral Evaluation System. SCL-90-R: Symptom Checklist-90-Revised. PSE: Present State Examination. SF-36: Short Form Health Survey-36.
The adverse event (AE) figures listed here are neuropsychiatric AE, where it is possible to elicit that data from the report. n.d.: not determinable.
There were 73 subjects; however 6 of these had used mefloquine at treatment doses. The remaining 67 had used the drug for chemoprophylaxis.
This was a follow-up study that only considered subjects who had submitted adverse event reports to the national drug regulator.