Cambridge gap-year student Alana Cutland's fatal fall from a light aircraft has sparked a debate about the potential side-effects of anti-malaria medication. Photo / Supplied
Anita Randall's twentysomething nephews and nieces were recently planning a trip round India, just like the first overseas adventure she had set off on 30 years ago in her early 20s. There was only one piece of advice that she gave them: "Don't take Lariam!"
Randall, now in her mid-50s and living in Kent, knows from personal experience just what havoc this anti-malaria drug can wreak in some young minds and lives. Mefloquine, also known as Lariam, she says, "took away 10 years of my life".
She has thus been drawn even more than most to reports last week of the death of Cambridge gap-year student Alana Cutland from Milton Keynes, who fell from a plane in Madagascar.
Cutland, 19, had been suffering, her uncle has confirmed, from hallucinations at the time, and the authorities in Madagascar are now said to be investigating if these could have been caused by Lariam, which was reportedly among her possessions and has repeatedly been linked in recent years with side effects including psychosis.
There is, though, still some confusion at this early stage in the investigation over whether Cutland might have been taking another antimalarial, doxycycline, also found among her things.
"Lariam had recently come on the market when I was going travelling," Randall recalls. "My dad was a GP, and he prescribed it for me because you only had to take one tablet a week from before you set off, rather than one a day, so I was less likely to forget. But from the moment I got off the plane in India, I started feeling odd and extremely anxious."
And it quickly got much worse. "I was having hallucinations, pacing up and down and acting in a peculiar way." At one stage, she says, she curled up in a ball on the bathroom floor, unable to breathe, and begged to be sent home. "I felt like my soul had been sucked out of me."
When Randall did make it back to England after a month, having completed the course of antimalarials, she was prescribed antidepressants, but fell into a deep clinical depression that necessitated her moving back in with her parents to be looked after. It was two years, she remembers, before "the fog" started to lift, three before she could take on a part-time job, and, she estimates, a whole decade before she stopped feeling so anxious.
It was only in the mid-Nineties, when BBC One's Watchdog publicly highlighted the potential serious psychological side effects of Lariam, that Randall finally felt she had been given the answer as to what had happened to her on her trip.
She survived to tell the tale. In 2003, a coroner's inquest in Swansea heard from the parents of previously "bright, vivacious" Cambridge student Vanessa Brunt, that she came back from a gap-year trip in the Far East, where she had taken Lariam, with "a haunted expression in her eyes". She committed suicide at the age of 22.
By that time, a growing chorus of concerns was being heard about Lariam. The comedian Paul Merton has spoken of how, in 1990, he had taken Lariam for a trip to Kenya and developed paranoia about being "a target for the Freemasons". He was admitted to a psychiatric hospital for six weeks as a result.
Many GPs and travel clinics now routinely advise patients not to take it. Lloyds Pharmacy, for instance, no longer provides Lariam through its online doctor service, "due to the various and unpredictable side effects" associated with its use. The Army, however, continued to prescribe Lariam to its soldiers to protect them from malaria when going into battle in Iraq and Afghanistan.
Johnny Mercer, the Conservative MP and former British Army captain who did three tours of duty in Afghanistan, spoke out publicly in 2015 to advocate an end to its use. "I've had a letter about once or twice a week," he said at the time, "from not only constituents but people all over the UK who have suffered or know someone who has suffered, they believe, as a result of taking Lariam."
As the new minister for veterans' affairs in Boris Johnson's Government, Mercer may now be able to complete that push for a ban. He may also be involved in the response to class-action lawsuits now under way from Army veterans who claim they have suffered severe side effects as a result of being prescribed Lariam.
Among others who claim to have suffered "pretty catastrophic" mental health issues after taking Lariam (as a civilian) is Bertie Dannatt, son of Lord Dannatt, who was the Army's chief of the general staff between 2006 and 2009. Lord Dannatt has subsequently apologised publicly to any soldier who was given the drug under his command.
"The evidence is mounting that Lariam is a primary cause of mental health issues, with many leading to suicidal tendencies or the actual committal of that tragic act," he says. "I have campaigned for years that the Ministry of Defence should cease prescribing it. The fact that it is a cheap alternative to better prophylactic drugs compounds the failure to exercise proper duty of care."
Cost may be one reason why gap-year students continue to take Lariam, suggests Dr Ashley Croft, who served in the Royal Army Medical Corps for 27 years. He is now a consultant in public health medicine and has carried out two detailed pieces of research on Lariam, which he says is "freely and cheaply available online under its generic name of mefloquine".
Current medical advice is that Lariam should only be prescribed in specific circumstances – "a drug of last resort" is how the Ministry of Defence has described it – and only after a one-to-one assessment of the individual by a trained professional to see if they have any existing conditions that might be exacerbated by it.
"But you don't get a one-to-one assessment when you buy it online," says Dr Croft, "and, for your sometimes slightly chaotic gap-year student trying to eke out a small travel budget, the warnings may go unheard."
In response to the speculation following the circumstances of Cutland's death, Roche, the Swiss pharmaceutical giant that brought Lariam to the UK market, reiterated the guidance that accompanied its distribution – that it "should only be prescribed by a healthcare professional after an individual risk assessment". However, the firm added that, since November last year, "we are no longer responsible for Lariam in the UK".
Several distinguished medical voices have also urged caution in rushing to blame Lariam.
"Malaria is a very serious disease and remains a leading cause of death in low-income countries, especially in Africa," says Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine. "For visitors to regions where there is a high risk of getting malaria, there is no doubt that the benefit/risk balance of taking antimalarial drugs is in favour of the recommended drugs."
All the currently effective drugs in preventing malaria, he says, "have adverse effects [but] serious ones are very rare. There is little doubt neuro-psychiatric effects can occur with mefloquine, but these are very rare."
But the profession remains divided. "Yes, malaria is a serious disease and, yes, Lariam works to prevent people catching malaria, but so do other drugs, such as Malarone and doxycycline," says Dr Croft. "They may be more expensive and have to be taken every day, but travellers can easily get into a routine. The alternatives do not carry the same psychological risks."
Lord Dannatt believes that the weight of concern over Lariam is sufficient for regulatory action. "That students on tight budgets are now buying this drug should lead the Government more widely to consider an outright ban."
Most British tourists entering a malarial zone this summer will be prescribed one of three antimalarials, says Prof David Lalloo, director of the Liverpool School of Tropical Medicine. These are: doxycycline; Malarone (known scientifically as atovaquone plus proguanil); or Lariam (mefloquine).
Malarone is the most popular option because its patent has recently expired. Doxycycline should not be taken by children under 12 or pregnant women, because it may affect bone growth. If possible, pregnant women should avoid any antimalarials during their first trimester.
Antimalarials should ideally be taken on a full stomach to avoid side effects, especially doxycycline, says Prof Lalloo.
It is important to follow the instructions: studies suggest only 20 per cent of travellers take antimalarials as often as they should.
All anti-malarials have side effects. Doxycycline and Malarone can cause stomach upset, nausea, headaches, skin irritation and mouth ulcers. Lariam has been linked with insomnia, anxiety, panic attacks, and even hallucinations.
If you are taking Lariam and think you are experiencing psychological side effects, Prof Lalloo says you may wish to seek medical advice, and investigate an alternative, but this should be weighed against the malaria risk where you are. Always seek advice from a specialist travel clinic or a GP with expertise in travel medicine before travelling.
Which antimalarial should I take?
Most British tourists entering a malarial zone this summer will be prescribed one of three antimalarial tablets, says Prof David Lalloo, Director of the Liverpool School of Tropical Medicine:
Doxycycline: taken daily, starting two days before you enter a malarial zone, and continuing for four weeks after you return. Not to be taken by children under 12 or pregnant women, because it may affect bone growth.
Malarone (known scientifically as Atovaquone plus Proguanil): taken daily, starting one or two days before you go and continuing for one week after you return. This is now the most popular option, says Prof Lalloo, because its patent has recently expired.
Lariam (Mefloquine): taken once a week, starting three weeks before you go, continuing for four weeks after you return.
If possible, pregnant women should avoid any antimalarials during their first trimester.
How should I take them?
Doxycycline should only be taken on a full stomach. Try to take Malarone and Lariam on a full stomach, too, but don't worry too much if you can't, says Prof Lalloo.
Alcohol has little to no effect, but you should avoid drinking too much while on any medicine.
And remember to actually take them – studies suggest only 20 per cent of people travelling in a malarial zone take the tablets as often as they should.
What are the side-effects?
Doxycycline and Malarone can cause stomach upset, headaches, nausea, skin irritation, and mouth ulcers. Lariam has been linked with insomnia, anxiety, panic attacks, and even hallucinations.
What do I do if I'm having side-effects?
If you are taking Lariam and experience side-effects "that you think might be anxiety or psychiatric-related", Prof Lalloo warns, stop taking them, seek medical advice, and look for another way of protecting yourself against mosquitoes.
Doxycycline and Malarone are less serious, and "you'd have to decide how severe the side-effect is."
For further advice
Seek advice from a specialist travel clinic or a GP with expertise in travel medicine, rather than just buying the pills over the counter.
WHERE TO GET HELP:
If you are worried about your or someone else's mental health, the best place to get help is your GP or local mental health provider. However, if you or someone else is in danger or endangering others, call police immediately on 111.
OR IF YOU NEED TO TALK TO SOMEONE ELSE:
• 0800 543 354 (0800 LIFELINE) or free text 4357 (HELP) (available 24/7)
• https://www.lifeline.org.nz/services/suicide-crisis-helpline
• YOUTHLINE: 0800 376 633
• NEED TO TALK? Free call or text 1737 (available 24/7)
• KIDSLINE: 0800 543 754 (available 24/7)
• WHATSUP: 0800 942 8787 (1pm to 11pm)
• DEPRESSION HELPLINE: 0800 111 757 or TEXT 4202
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