By Julian Lewis
Journal of the Royal United Services Institute, vol.167, no.3 – September/October 2022
Andrew Marriott: If you Wake at Midnight, Austin Macauley Publishers, 2022, 367pp.
How many times must a medical disaster be exposed to public view, and how many decades must elapse, before remedial action is taken and restitution made? Far too many, if the NHS contaminated blood scandal and the still unresolved vaginal mesh horrors are any guide. In the case of those injured or bereaved by the anti-malarial drug mefloquine – commercially branded as Lariam – the sheer longevity of the suffering has enabled some to acquire highly relevant skills. One such person is Jane Quinn, widow of a major driven to suicide in 2006. She became a clinical neurotoxicologist supporting Lariam victims internationally and testifying to parliaments in Canada and Australia where she resettled after her loss. Another – the author of this book – damaged by the drug in Sierra Leone, left the army after 30 years and qualified as an archaeologist. In that capacity, Andrew Marriott knows how to delve into the mire, unearth the evidence and reconstruct the history of this murky affair.
Soon after completing a year on mefloquine, supposedly the only effective anti-malarial for Sierra Leone where he served throughout 2003, Marriott experienced a transitory urge to leap from the balcony of a conference hotel. It followed incessant vivid nightmares that began almost from the outset of taking Lariam. This pattern of sleep disturbance has persisted ever since. When prescribed the medication, he was told of a 1-in-25,000 chance of ‘serious psychotic reactions’. Experience proved this to be a massive underestimation:
‘Only when I returned home at the end of my tour did I learn from civilian medical practitioners that other, safer, anti-malarials were freely available’ (p. 30).
As part of the chain of command, he had therefore been ‘complicit in the imposition of a toxic drug regime on subordinates’ (p. 30).
After the Allies lost access to naturally derived quinine when the Dutch East Indies were overrun in the Second World War, US industry came up with a synthetic alternative, Atabrine (quinacrine), under the imperative of protecting personnel against the deadly risk of malaria. 5 Despite severe side effects, it continued to be marketed for many years. Marriott suggests that it accounted for Orde Wingate’s serious attempt at self-harm and Alan Brooke’s grave concern for his mental state. He relates how the pressure of the Vietnam War similarly accelerated the development of Lariam (mefloquine), which was finally approved for use in the US in 1989 – the same year it was licensed for use in the UK. Only in 2001, were ‘randomised controlled trials’ carried out involving healthy civilian volunteers. Four years later, on a second mission to Sierra Leone, Marriott was offered Lariam again, despite his medical records clearly showing its enduring effects on him. By then he knew enough to demand one of the safer alternatives but was appalled later to discover that mefloquine was routinely and indiscriminately being issued to soldiers.
Despite a Pension Appeal Tribunal ruling, soon after discharge, that he had been partly disabled by ‘nightmare disorder’ caused by Lariam, this formal diagnosis did nothing to persuade military medics or ministers, then or subsequently, to act against the hazards illustrated by Marriott’s case:
‘Moral and health issues aside’,
Marriott concludes,
‘the use of this medication was quite incompatible with our military fighting doctrine; in fact it seriously undermined it, affecting not just the performance of soldiers taking the drug but eroding confidence and team cohesion across whole fighting units’ (p. 67).
Marriott’s findings, from extensive direct experience, coincide in all main particulars with the those of Peta Bathie whose March 2020 article, ‘Military Safety: A Systems Perspective on Lariam’, in the RUSI Journal described Lariam as ‘an antimalarial drug that has a safety profile characterised by a predominance of neuropsychiatric adverse reactions’ and firmly recommended its discontinuation. The frightful reality behind that description is illustrated by Marriott’s detailed accounts of suicides attempted (sometimes successfully), personalities transformed, relationships wrecked and careers destroyed. They are harrowing to read but we dare not turn away.
This reviewer must now declare an interest, having initiated the House of Commons Defence Committee inquiry, ‘An Acceptable Risk? The Use of Lariam for Military Personnel’, on this subject. Its May 2016 report fully accepted that the Ministry of Defence (MoD) has a duty of care adequately to inoculate service personnel on overseas operations and that this ‘will never be without the risk of detrimental side-effects’. Nevertheless, in the case of malaria and mefloquine ‘the MoD’s current policy has got that balance wrong’ and shows ‘a lamentable weakness’ in that duty of care. We acknowledged ‘a very limited number of occasions when its prescription may be necessary’ but concluded that Lariam should be designated as a ‘drug of last resort’ and prescribed only if three conditions were met. First, only if the recipient cannot tolerate any of the available alternatives; second, only after a face-to-face Individual Risk Assessment, as required by the manufacturer; and finally, only after the recipient had been made aware of the alternatives and given the choice between Lariam and another suitable anti-malarial.
After the report was published, statistics supplied to the committee suggested a marked decline in the numbers of service personnel prescribed Lariam rather than its alternatives, with hardly any cases of a face-to face interview not being held. Yet, there are worrying signs of attempts to rehabilitate the use of mefloquine and the fight is far from over. Marriott places particular emphasis on a 2014 European Medicines Agency report, ‘Updated PRAC Rapporteur Assessment Report on the Signal of Permanent Neurologic (Vestibular) Disorders with Mefloquine’. The report, which was not brought to the inquiry’s attention, states that:
'Mefloquine may induce psychiatric symptoms such as anxiety disorders, paranoia, depression, hallucinations and psychosis. Psychiatric symptoms such as nightmares, acute anxiety, depression, restlessness or confusion have to be regarded as prodromal [an early warning] for a more serious event. Cases of suicide, suicidal thoughts and self-endangering behaviour such as attempted suicide … have been reported.' (p. 29 of the European Medicines Agency report)
Far from being a temporary price to pay for protection against malaria, therefore, several frequently experienced side effects of Lariam had been known for nearly a decade to be portents of potentially fatal outcomes for its recipients and those who might be affected on operations by the impaired judgement of their comrades. Indeed, Marriott convincingly demonstrates that this prodromal danger had originally been known by 1990 but was removed from relevant guidance in the UK between 1996 and 2013 – exposing a generation of service personnel to significantly greater risk.
If You Wake at Midnight: The Lariam Wonder Drug Scandal is a passionate and persuasive indictment. At the end of a meeting with representatives of the drug’s manufacturers, one of Marriott’s companions asks each of them:
‘Would you take this drug? Is this something you would ask your families to take?’ (p. 231).
Not one was willing to answer.
Julian Lewis chaired the House of Commons Defence Committee, 2015–19.