The Lariam hazard: is the risk too big?

Is an anti-malarial linked to psychosis, anxiety and depression simply too big a risk to take?

Tim Notee can pinpoint the exact moment when he started to lose his mind. He was preparing for a university trip to Ghana and was struggling to make simple packing choices. Tim, who was a student in the Netherlands at the time, put it down to the stress of getting ready for the seven-week trip. It hadn’t occurred to him that the confusion was connected with his prescription for the antimalarial Lariam, which he had started taking prior to his departure. 

In fact, taking Lariam had seemed a straightforward decision. “They [the travel clinic] gave me a few options but I thought it would be cheaper to stick to the Lariam because I only had to take seven tablets,” Tim explains. “It didn’t seem like a huge deal to take Lariam; they talked lightly about it.” And even at a follow-up consultation three weeks later, Tim had no concerns about side effects.

But Tim’s mental health soon took a turn for the worse. A week after arriving in Ghana, Tim found he was unable to sleep, his mind was racing and he felt isolated. He remembers all too well the feeling of desperation. “I was an over-exaggerated version of myself – I wanted to tell people what was happening to me but I couldn’t express myself; I was paranoid and hopeless,” Tim recalls. 

It didn’t take long for fellow students to raise the alarm. This was the beginning of an ordeal that would last a year for Tim. 

He was admitted to hospital, where he would remain for the next few months in Ghana and in the Netherlands. To combat the symptoms, he had to take medication that made him feel “totally flat”. He only stopped the medication in October last year and is now, finally, drug-free. 

Understandably, the experience has made Tim strongly opposed to the prescribing of Lariam, which he believes is “not something you’d want in your system”. 

He is not alone in his views – others who have suffered similar experiences have called for the withdrawal of the drug, as have healthcare professionals concerned over its effects. But the antimalarial is still prescribed by GPs and pharmacists and is, in fact, recommended by Public Health England. So is it time to reconsider our position? 


“The anxiety and hallucinations were dulled by the deep clinical depression. I had to give up my job and my flat and move back in with my parents to be nursed”

Anita Randall
Patient who took Lariam in 1990


Anxiety and hallucinations

Opponents of Lariam make a compelling case for its withdrawal. Fifty-year-old Anita Randall from Tunbridge Wells was one of the first people to take the drug following its launch in the UK in 1989. She took the antimalarial by manufacturer Roche on the advice of her father, who was a GP, in 1990. Then, it was a widely used antimalarial and reports over psychiatric side effects had not yet surfaced.

Soon, Anita began to feel anxious about her trip – a feeling that only worsened with time. Vivid nightmares, panic attacks and depression plagued her throughout the holiday and did not subside on her return to the UK. Her symptoms forced her to take the antidepressant Seroxat for 18 months. “The anxiety and hallucinations were dulled by the deep clinical depression. I had to give up my job and my flat and move back in with my parents to be nursed. I continued to experience panic attacks and bouts of depression for the following five to seven years,” Anita explains. 

Anita’s experience could easily be dismissed as an isolated case. But the fact that objective healthcare professionals share her fears suggests the problem goes far deeper. Lloydspharmacy no longer provides Lariam through its online doctor service “due to the various and unpredictable side effects” associated with its use. The multiple said there were safer alternatives to Lariam that provided “equally effective protection against malaria without posing these risks”.

And Remington Nevin, a consulting physician epidemiologist and specialist in antimalarial toxicity based in Baltimore, Maryland, US, also has doubts over the safety of the mefloquine-based drug.

“It is often erroneously believed, even by experienced pharmacists and physicians, that mefloquine is safe to use among those who have no history of psychiatric disturbances,” Dr Nevin explains. “We know from Roche’s own material that Lariam may induce psychiatric symptoms in a sizeable minority of perfectly healthy people.” 

Indeed, Roche’s patient information leaflet says sleeping problems may occur in more than one in 10 patients and psychiatric symptoms such as paranoia are listed among its side effects (see The side effects of Lariam, above panel), although their frequency is not known. Roche adds that a “small number of patients” experience depression, dizziness or vertigo and a loss of balance that can persist for months after they have stopped taking Lariam.

From his experience, Dr Nevin believes there is a “startlingly high rate” of symptoms requiring discontinuation of the drug. He laments that these incidents seem to have “mostly escaped the notice of UK authorities”, which still recommend its use.


“We know from Roche’s own material that Lariam may induce psychiatric symptoms in a sizeable minority of perfectly healthy people”

Dr Remington Nevin
Consulting physician epidemiologist and specialist in antimalarial toxicity, Baltimore, US


A ‘special occasion’ drug 

For the time being, there is no sign of Public Health England changing its views on Lariam, which it describes as an “extremely effective antimalarial”. Unless any new data comes out, the body says it will continue to recommend mefloquine on the condition that patients undergo “a stringent individual risk assessment”.

Roche says the available data comes down on the side of the drug. A safety assessment published by EU health authorities in 2013 reinforces previous guidance that the “benefits of Lariam outweigh the potential risk of the treatment”.

Richard Dawood, medical director at Fleet Street Clinic and a travel medicine specialist, believes this is true in very specific cases. He wonders whether Lariam’s “gloomy reputation” has been blown out of proportion by Roche’s handling of the controversy when it first arose. “There was possibly a lack of understanding and response to the side effects,” he says. “The drug company handled [the situation] poorly; it could have done something to increase awareness and make sure it was prescribed properly.” 

He believes Lariam has its place among “people who have taken it before and who are happy with it”. “This is a special occasion antimalarial,” explains Dr Dawood. He might recommend it for a three-month trip, when patients will appreciate that Lariam only needs to be taken once a week. 

Pregnant women also benefit from the drug – because other antimalarials are not safe to use. Without Lariam, you’d end up advising pregnant women not to travel, Dr Dawood says. But he stresses that prescribing mefloquine is not the norm. “There are situations where it is appropriate to take this drug; it is not given lightly,” he says.

For this reason, he would no longer support the prescribing of Lariam on a wide scale. “Ninety-five per cent of people who leave my clinic do not have mefloquine offered; relative to the other options, it is not suitable. Why would I pick a drug that you have to take two and a half weeks before you go and four weeks afterwards?” he says. 

All things considered, Dr Dawood believes we should not restrict the choice of antimalarials by withdrawing Lariam. “There are few things we do that are entirely risk-free – it is a case of informing people adequately and giving them the information that they need,” he says.

Safe prescribing 

It is difficult to come to come to a definitive conclusion about Lariam. While it is hard to gloss over the disturbing case studies of psychiatric disturbances, there are times when it may be the most appropriate drug available. So is the answer further education and more rigorous testing? 

Dr Dawood believes so. When prescribing Lariam to someone for the first time, he would make sure they were in the UK long enough to report anything that disturbed them before travelling. He would also take note of their medical history, and make sure they were “aware of all the small print”. “I’d talk to them about alcohol and marijuana use, too, which are all factors in the adverse effects,” he adds.

Dr Nevin goes one step further in his recommendations. He would like patients to receive a test prescription prior to travel “with careful neuropsychiatric evaluation between the doses”.

Opinions on the correct precautions may vary, but the consensus is that, if healthcare professionals choose to prescribe Lariam, they must give out as much information as possible. Frank conversations about the side effects are important, along with carefully considered advice and monitoring. Once the patient is informed, it is up to them whether it is worth taking a chance on the drug. 

The case of Tim Notee highlights just how catastrophic the consequences can be when patients are unaware of the dangers. “It has done so much damage and there are people whose lives are just ruined because of it,” he says. “I’m lucky to have recovered.”

 

3 Comments

Amal England, Public Relations

With the increase in resistance to antimalarials, the Pharmaceutical Industry must look for safer novel antimalarials. The incentive is there- global travel is projected to increase phenomenally. There already is a novel antimalarial in the pipeline, one which can target the parasite at multiple points in its lifecycle. I wonder if the global drive by the likes of WHO, to deal with vector is affecting the willingness of the Pharmaceutical Industry to invest in novel antimalarial.

London Locum, Locum pharmacist

Malaria kills mainly Sub Saharan Africans so Drug companies/Governments etc.... are not particularly bothered. You need a nice new disease that kills Westerners almost exclusively for companies to really come to the fore.(Think obesity related diseases)

Angela Channing, Community pharmacist

Wouldn't touch it with a barge pole!

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