Opportunities missed to review mefloquine use in the UK military

The antimalarial drug mefloquine (Lariam) is notorious for inducing neuropsychiatric effects in some users[1]
. From 1993 onwards it was dispensed routinely to around 2,000 UK military personnel each year, mostly soldiers training in the Nanyuki Highlands of central Kenya (and where, ironically, there is almost no malaria).

The
Pharmaceutical Journal has performed a valuable service in highlighting the difficulties facing armed forces personnel who were damaged by mefloquine, and who are now seeking compensation[2],[3]
. As of this month, there are over 1,000 serving and retired military personnel in this category.

On 13 September 2016, BBC Radio Four’s Today programme featured an interview between presenter John Humphrys and a representative from the Ministry of Defence (MoD)[4]
. Humphrys asked the hapless ministry spokesperson if he accepted that its mefloquine dispensing demonstrated “long-term malpractice for more than 20 years”.

The MoD man dodged the question and asserted that in the past ten years the “vast majority” of its antimalarial prescriptions were accomplished “entirely correctly”
[4]
.

The lawyers are likely to take a different view and argue that there was a specific date in time — in legal parlance, the date of knowledge — when the MoD should have known that mefloquine was uniquely dangerous in deployed troops, after which mefloquine should have been prescribed only with the utmost caution, if at all. When was this date of knowledge? I offer three possibilities:

On 1 October 2001, the first ever randomised controlled trial of mefloquine in tourist and general travellers was published[5]
. It showed a clear excess of neuropsychiatric events in mefloquine users. Hastily, some national armies, e.g. Denmark and The Netherlands, stopped prescribing mefloquine to their troops.

On 1 October 1996, the Committee on Safety of Medicines (CSM — the Medicines and Healthcare products Regulatory Agency’s forerunner) advised UK doctors to warn patients who were being prescribed mefloquine about the drug’s neuropsychiatric side effects[6]
. Plainly, the MoD did not do this.

On or around 20 December 1995, a UK soldier who was taking mefloquine during an Army-run clinical trial in Kenya killed himself. This came at an acutely embarrassing time for the MoD, since the previous month the BBC television programme Watchdog had highlighted the neuropsychiatric dangers of Lariam[7]
. As the Defence Committee was recently informed[8],[9]
, the MoD seemingly panicked, and concealed from the responsible authorities (Coroner, the CSM) this fatal outcome in a controlled clinical study. Doubtless, it hoped the problem would go away. It didn’t.

Ashley Croft

Consultant public health physician – defence committee witness

Served in the Royal Army Medical Corps from 1986–2013

University of Portsmouth

References

[1] Nevin RL & Croft AM. Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives. Malar J 2016;15:332. doi: 10.11 86/ s1 2936-016-1391-6

[2] Croft AM. Mefloquine, madness and the Ministry of Defence. The Pharmaceutical Journal (12 November 2015)  doi: 10.1211/PJ.2015.20200021

[3] Andalo D. Mefloquine should be last resort for military personnel, MP committee says. The Pharmaceutical Journal (26 May 2016) doi: 10.1211/PJ.2016.20201208

[4] BBC Radio 4 Today programme 13 September 2016. Available at: http://www.bbc.co.uk/programmes/b07v07ny (accessed 16 September 2016)

[5] Overbosch D, Schilthuis H, Bienzle U et al. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomised, double-blind study. Clin Infect Dis 2001;33:1015–1021. doi: 10.1086/322694

[6] Committee on Safety of Medicines. Mefloquine (Lariam) and neuropsychiatric reactions. Current Problems in Pharmacovigilance 1996;22:6. Available at: http://webarchive.nationalarchives.gov.uk/20141205150130/http:/www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con2023218.pdf

[7] Reid AJ, Whitty CJ, Ayles HM et al. Malaria at Christmas: risks of prophylaxis versus risks of malaria. BMJ 1998;317:1506–1508. doi: 10.1136/bmj.317.7171.1506

[8] Defence Committee. Lariam inquiry HC 567. Oral evidence given by Dr Ashley Croft, Lieutenant Colonel (Retired) A G Marriott MBE, Trixie Foster, Dr Remington Nevin (8 December 2015). Available at: http://data.parliament.uk/writtenevidence/committeeevidence.svc/evidencedocument/defence-committee/an-acceptable-risk-the-use-of-lariam-for-military-personnel/oral/25763.pdf

[9] Defence Committee. Lariam inquiry HC 567. Written evidence submitted by Dr Ashley Croft MD and Dr Remington Nevin MD (4 February 2016). Available at: http://data.parliament.uk/writtenevidence/committeeevidence.svc/evidencedocument/defence-committee/an-acceptable-risk-the-use-of-lariam-for-military-personnel/written/28487.pdf (accessed September 2016)

Last updated
Citation
The Pharmaceutical Journal, PJ, October 2016, Vol 297, No 7894;297(7894):DOI:10.1211/PJ.2016.20201729