Editorial Note: This is the transcript of a program broadcast as The Lariam Legacy on BBC Radio on March 31 2015. The narrator is Victoria Derbyshire. The featured drug is the anti-microbial Lariam, mefloquine. Mefloquine is closely related to the Fluoroquinolone’s Levaquin and Cipro. See previous RxISK posts on Lariam History, Lariam Hell and Flox-Tox. Atabrine was the anti-malarial used by the Army before Lariam.
VICTORIA (Buzzing noise in background)
Bear with this irritating little mosquito while I try to set the scene.
Imagine for a moment that we are visiting a tropical country, and this mosquito is a potentially lethal one carrying malaria. Malaria still kills more than half a million people each year. That’s not a disease I want to risk getting. So I take all the usual precautions: sleep under a mosquito net, use insect spray, and sometimes I need the extra protection of anti-malarial tablets.
But what if those tablets came with some alarming side effects? (extremely strange, background voices, disjointed, speaking of severe nightmares, hallucinations, dark feelings, terrifying nightmares and other disturbing experiences)
And those nightmares are just the beginning.
One of the most effective drugs against malaria is Mefloquine. You might know it by its trade name, Lariam. It got a lot of bad press in the 1990s when some travellers reported very disturbing side effects after taking the drug.
Female voice
He thought that his lips had turned to liquid; and he actually felt the pain as if his whole face was disintegrating…
Male voice
Cardiac problems, paralysis, hallucinations, complete panic attacks…
Another male voice
I couldn’t remember who I was or where I was…
Another male voice
Some kind of psychotic state that I had never had in my life ever before…
********
VICTORIA
Not everyone will experience side effects, and severe reactions are rare. Lariam, or Mefloquine, remains a very effective anti-malarial. And for those who can tolerate it, it’s good value, and only needs to be taken once a week.
For those who don’t want to risk it, there are good, safe alternatives. Many travellers use Doxycycline or Malarone, which have to be taken daily. The point is, most people have a choice.
(Military voices in background, parade ground style)
But the vast majority of serving soldiers in the British Army don’t have a choice. The decision as to which anti-malarial is appropriate for a tour of duty is of course made further up the chain of command for the unit as a whole. And, apart from a few exceptions on medical grounds, all will take the same drug.
(Military voices again)
What we have discovered is that for over two decades British soldiers have been prescribed a drug that can cause serious neuropsychiatric disorders.
The manufacturer, Roche, warns of hallucinations, psychosis, and suicide. And for some, the Lariam Legacy may be permanent.
There is a growing clamour for the Ministry of Defence to stop using the drug. Those calling for a ban include General Lord Richard Dannatt, former head of the British Army; as well as regular soldiers and their families.
Dannatt
If Lariam was a piece of equipment, it would have been banned years ago. When I load a rifle, and put a bullet into the chamber, what I don’t want is that thing to either degrade the weapon system or me. I certainly don’t want it to blow up in my face. And that’s the issue with Lariam.
********
VICTORIA
Roughly two and a half thousand British troops are given Lariam (Mefloquine) each year.
And it’s not just those sent to fight wars. British troops are regularly sent to malarial zones such as West Africa on exercise.
Eighteen months ago drug regulators strengthened their warnings on Mefloquine.
Some psychiatric side effects such as nightmares and depression could be a sign of something more serious they said, and some symptoms could last long after taking the drug.
In America this resulted in a boxed warning, the most serious kind, being added to the drug label.
The US Army drastically reduced its use of Mefloquine. It’s now only given to soldiers who can’t tolerate the alternatives. And it’s been banned altogether for US Special Forces.
But in the UK nothing has changed. So when we heard about a retired Army Officer desperate for the MoD to listen we went to investigate.
(Traffic noise)
Hi Andrew. It’s Victoria. How are you? Good, so I’m here. Shall I meet you outside the entrance?
Andrew Marriott is a retired Lieutenant Colonel. He served in the Army for over thirty years (military conversation in background). In 2003 Andrew was sent to Sierra Leone and he was prescribed Lariam before he left. He noticed the side effects straight away, starting with very vivid dreams.
Marriott
Things got worse and worse; problems with balance, dizziness, losses of memory, and problems with anger management.
Victoria
Did you think this is because of the Lariam?
Marriott
I knew it was because of the Lariam.
Victoria
How?
Marriott
Well, I could see when I arrived in Sierra Leone that there were personnel whose performance was degraded to put it mildly by the fact that they were taking this drug.
Victoria
In what way?
Marriott
In the sense of their confusion, minor acts of violence within the team. I don’t expect to see officers striking other officers or people that we are attempting to mentor and teach.
********
VICTORIA
Andrew was convinced that what he saw was very unusual, but was it? After all, Sierra Leone was a hot, humid country in the aftermath of a civil war.
Through social media, we made contact with another officer who had done the same job as Andrew but a year earlier.
Johnny Aisbitt, a major at the time, described what it was like.
Aisbitt
The entire country was largely desolate, the stability was so fragile that it didn’t extend many miles outside of Freetown.
Victoria
If someone says to you this drug will protect you from catching malaria but you might have vivid dreams do you sort of shrug and go “ok, that’s fine”?
Aisbitt
Yes, absolutely.
Victoria
And do you remember anything odd when you started to take it then, or not?
Aisbitt
Gosh, yes. Absolutely. Vivid, psychotropic, I suppose, dreams through the night. Lariam was taken once a week, and we would try to schedule that day for a time when we weren’t going to be driving on those extremely dangerous roads over central and eastern Sierra Leone. Because we would feel dreadful nausea, sometimes disorientation.
Victoria
Over time, as you had been taking Lariam, did you notice anything different about you?
Aisbitt
Certainly. I started to have real difficulty sleeping, the fun element of hallucinogenic dreams had certainly paled very quickly (laughs) and I was experiencing appalling mood swings. It wasn’t even to do with minor frustrations, which one can feel even just operating in such a hostile, such a hot, you know, humid environment. There was no logic to those flashes of rage. I felt it was really impairing my ability to function.
********
VICTORIA
So now I was really intrigued. Here were two officers saying they were given a drug that seriously affected their behaviour, and in their view their professional performance.
But compared to the other risks soldiers face these seemed like pretty minor inconveniences.
Not according to Dr. Remington Nevin, whose research on Mefloquine has influenced US policy.
Nevin
Seemingly mild symptoms such as vivid dreaming, or perhaps mild anxiety, or sense of unease. This is often the first warning sign, possibly the only warning sign, of the drug’s impending toxicity, which can build very quickly to a fulminant psychosis marked by mania, paranoia, dissociation, and even risk of a death through suicide.
********
VICTORIA
So I’ve got some pills here. I’m just going to have a look at the Patient Information Leaflet for Lariam.
“Warnings and Precautions: Take special care if you perform activities requiring alertness and coordination, and spatial awareness; such as driving, piloting an aircraft, operating machinery, and deep sea diving. Because Lariam can cause dizziness, loss of balance, and mental problems.”
Which is presumably why the British Military do not prescribe Lariam to their divers and their air crew. But why are soldiers still given them, because they operate machines, they operate weapons?
Croft
Well I consider an SA80 rifle to be a complex piece of machinery which is lethal.
Victoria
Dr Ashley Croft has asked the same question.
Croft
And those cautions ought to apply to soldiers carrying rifles, just as they do to air crew and divers.
Victoria
He’s an expert in tropical medicine, who has got twenty seven years of army experience behind him, as a public health physician.
Croft
The manufacturers of Mefloquine are admitting that one in ten patients will experience very common side effects like sleeping problems; a very great problem if you’re a soldier on guard duty and you’ve got a live weapon. Vision problems, and that is some difficulty to a soldier, of course it is.
Victoria
But that risk to some users is minimal and perhaps particularly minimal compared to the other risks that a soldier might be exposed to.
Croft
Well if you are talking about a battalion of soldiers comprising six hundred men and women, that means that maybe six or ten of them will be experiencing very severe side effects that can include psychosis, suicidal ideation, concentration difficulties, difficulty in seeing. These are people with a loaded weapon who can perform very dangerous acts on themselves or on others.
********
VICTORIA
But there’s no army in the world that has banned this drug altogether. Could that be because soldiers themselves are masking what’s really going on?
(President Bush: Deliberate and deadly attacks which were carried out yesterday against our country…)
Lee
We made a pact if we were to get surrounded by the Taliban then we were going to shoot each other.
Victoria
Lee was involved in the very early stages of what George Bush called “The War on Terror”
(Bush: Freedom and democracy are under attack…)
Victoria
Dropped into Afghanistan, for quick missions with US Special Forces
Lee
We drew straws and the one with the shortest straw shot himself sort of thing, you know.
Victoria
And you made that pact because that was preferable to being captured by the Taliban?
Lee
Yes. Tortured, yes. But to function correctly we decided as a team that we would not take Lariam.
Victoria
Why did you think that taking Lariam would mean that you wouldn’t be able to function properly?
Lee
Because of the side effects. We were in a high threat environment and we just couldn’t afford to carry anybody who wasn’t functioning correctly.
Victoria
Did you say anything to anyone?
Lee
No, nothing at all. That’s the thing with the Forces. It’s all about not complaining, getting your head down and getting the job done.
********
VICTORIA
Lee’s attitude was typical of the people we spoke to. Soldiers don’t complain. They get on with it, and they obey orders. But that makes using a drug like Lariam tricky. Because to be used safely it needs careful monitoring. If someone does experience any side effects the manufacturers stress that they must stop taking it and see their doctor. Even for seemingly trivial effects such as bad sleep or dizziness.
Dr Remington Nevin says this isn’t easy for a soldier to do.
Nevin
Soldiers who believe that their commanders and medical officers may attribute those symptoms to things such as cowardice or malingering certainly are going to have strong disincentives to reporting these side effects, and this is dangerous for two reasons.
The first is of course that that soldier is unlikely to follow the guidance to discontinue the medication and switch to a safer daily drug. But, second, the community then develops an unnatural impression of the drug’s safety. If the medical officers do not hear of side effects they conclude that the drug is safe, but it’s quite possible that their personnel may be suffering very disturbing side effects which they are afraid to report.
********
VICTORIA (Sound of bagpipes)
Jane Casperson-Quinn married her childhood sweetheart. She’d known Cameron since they were both fourteen.
Jane
He had a very active sense of public duty. He was the sort of person who held open doors for old ladies and took toddlers’ buggies up the escalators on the Tube.
Victoria
But when Cameron returned home from an exercise to Kenya in 2001 something had changed. Lariam had given him terrible nightmares while he was away, but he brushed them off, saying others had suffered far worse. And he continued to take the last few pills as prescribed.
Jane
He came home from work one afternoon and sat on the sofa and put his head in his hands and said to me, “I just don’t feel that I can go on anymore. I don’t want to live. I don’t understand why I feel like this.” As a neuroscientist working in research I was aware that there had been significant adverse psychiatric side effects reported and I immediately said to him: “Look, I think you need to stop taking this drug. I’m one hundred per cent sure that’s what’s caused how you’re feeling now. And you need to go in and tell your MO that this is the effect that this has had.”
Victoria
Cameron did stop taking the drug, but he refused to go and tell his MO, or Medical Officer, about his symptoms.
Jane
He was heading towards promotion at that point; and he felt that that would have a very serious impact on his ability to be considered for promotion if he had had some sort of mental health episode.
Victoria
Once he stopped taking the Lariam, did those overwhelming thoughts that he described to you, did they subside?
Jane
They did. What was interesting, though, was a general kind of creeping paranoia, and the dreams persisted. He would commonly wake in the morning having had a very restless night’s sleep. Then his explanation was just: “Oh, I had Lariam dreams again”. And he would be subdued for the rest of that day. And that continued right up until the point of his death.
Victoria
In 2006 Cameron took his own life while Jane and their two young daughters were downstairs clearing up the dinner. He’d given no warning and left no note. But, according to his wife, that morning he’d complained of Lariam dreams in the night, and problems with his vision. Doctors told Jane it was likely Cameron had suffered a psychotic episode.
The Procurator Fiscal, the Coroner in Scotland, wrote to Jane offering to meet her.
Voice representing Procurator Fiscal reads: “There are obviously issues in relation to the side effects of Lariam which are, it would appear, recognised in the warning sheets supplied by the manufacturers. There is obviously an issue with which I cannot become directly involved as to whether or not the Army were right to require or encourage their employees to take such a drug effectively in the course of their employment.”
********
VICTORIA
Suicides and suicidal thoughts are the most tragic potential side effects listed by the manufacturer Roche. But they don’t demonstrate the danger of ignoring the warning signs.
Others like Andrew Marriott have experienced lasting side effects.
Marriott
Typically since about mid 2003 I have not had a single undisturbed night of sleep. I will..
Victoria
Since 2003?
Marriot
Since 2003. I will typically wake five to six times and actually the condition that I’ve got has been described as “Nightmare Disorder”. There are some aspects that are so unpleasant, that nobody knows what they are.
Victoria
But forgive me, but it’s just a dream. People may have said that to you before and I don’t wish to sound dismissive.
Marriott
Oh yes. It is. But I would ask anyone to attempt to try to tolerate that sort of thing almost night after night after night.
Victoria
Did you tell anyone?
Marriott
Oh, indeed, yes. Yes. I told the medical team that there were problems with my team, with me. And I was told there was no alternative to Lariam.
********
VICTORIA
There was even then a perfectly good alternative. Johnny Aisbitt who’d been in Sierra Leone a year before Andrew, was given it when he complained to the doctor.
Aisbitt
The notes say “Wishing to stop Lariam, having problem with mood swings and temper. Altered sleep patterns and vivid dreams. Slowly getting worse. Short term memory loss. To move to Doxycycline 100mg and advised on side effects”.
Victoria
And so you were allowed to stop taking Lariam?
Aisbitt
Yes. I was. I was very fortunate. Yes. I know that a large number of my fellow team members were advised to remain on the drug. Many of them complained of ever increasing issues.
********
VICTORIA
Many soldiers admit not reporting their side effects. Others have sometimes been ignored when they do. And in researching this programme we’ve come across many accounts of soldiers simply ditching their tablets altogether, preferring to risk malaria.
So how does the Army know how many soldiers are really affected?
(Traffic noises)
I’m here at the offices of the Medicines Regulator, that’s the MHRA, and it’s here that bad reactions to any medicines are supposed to be reported. And the man in charge of that scheme, Mick Foy, has agreed to tell me how it works. (Traffic noises cease)
How serious would the side effects that have been reported through the Yellow Card Scheme be if I was taking an anti-malarial and it was giving me vivid dreams. Would I really report that on the Yellow Card Scheme?
Foy
You could do, because that may be an indication of something more serious. We look at every case. We add it to our database, and we run statistical programs across that data to identify signals, i.e. the drug event combinations that we need to investigate as a priority.
Victoria
What percentage of under-reporting do you think there might be out there?
Foy
Only one in ten get reported.
Victoria
But if so many don’t report, if there’s such a huge level of under-reporting, how is any of the work that you do here valid?
Foy
Statistically we are able to pick up signals. It doesn’t require full reporting to identify issues. The scheme started in the wake of Thalidomide and there’s not been a disaster of that nature since, because of the reporting that’s taken place and the ability to take action on those types of issues.
Victoria
On this form then, is there anything on here that would help you identify if you were getting reports of adverse reactions from a particular community; for example the British Army?
Foy
Often the reporter is an indication of where that case has taken place, for example a hospital doctor, a nurse in the community. So if it was coming from the Army, the reporter may well be based in an Army base. The more information that’s provided helps us build up that picture.
********
VICTORIA
Ministry of Defence guidance says “Medical Officers are to report any adverse reactions to anti-malaria drugs using the Yellow Card Scheme”.
Andrew Marriott reported his adverse reactions to Lariam to several Army doctors, both in Sierra Leone and back home in England. And his condition was acknowledged by the Government in terms of a disability payment. But he claims not one of those Army doctors reported his case to the Regulator.
Marriott
I checked with the MHRA to see whether or not a Yellow Card had been raised for me and as far as they are aware they have not.
Victoria
And what do you think of that?
Marriott
I think it’s disgraceful.
********
VICTORIA
Andrew also asked the MHRA how many Yellow Cards had been submitted from the Military in relation to Lariam or Mefloquine in the decade from 2001 to 2010. The answer was eight.
Now those figures aren’t entirely reliable, as they just depend on the address given on the form to identify the report coming from the Military.
But according to those figures the Military made no Yellow Card reports in relation to Lariam in 2009, the year when Scott’s life changed forever…
Scott
We were told that if we felt we had any problems, i.e. anger issues or alcohol problems or things like that, they would be able to prescribe an alternative. I do have slight anger issues, so I did raise that. The response I received to that was “Oh, you’ll be fine. Carry on, just take it”.
Victoria
It was three weeks before Scott experienced any side effects.
Scott
As a group we went out for an evening out, enjoying some entertainment and drinks and the following morning I woke up with intrusive thoughts which I had never had before. That I had done something whilst drinking which, you know, was inappropriate, or could land me in trouble. I didn’t sleep for virtually two weeks. I couldn’t handle any arms or weapons. I would be in the Medical Staff’s room about nine to ten times a day, just seeking reassurance.
Victoria
After two weeks medical staff sent Scott back to the UK. He was later diagnosed with Obsessive Compulsive Disorder.
Scott
Approximately ten to eleven months down the line it felt that this was obviously not going to go away. So I was discharged from the Armed Forces medically and basically had to start my life all over again.
********
VICTORIA
Scott blames Lariam for the end of his career. He claims he never wanted to take it, but his request for an alternative was turned down.
And that’s the vital difference between being a tourist choosing to take it, fully aware of all the precautions, and a soldier who has to obey orders.
(Conversation in background)
Lee was the soldier who ended up ditching his Lariam because he was worried that he wouldn’t function properly in Afghanistan.
Lee
It was just a case of “Here you are, there’s your meds”. No brief.
Victoria
Do you remember who handed them out to you?
Lee
Oh, God. I can’t remember. I think it could be the Sergeant Major?
Victoria
And you accepted that?
Lee
Yeah. At the end of the day you are taking the Queen’s Shilling aren’t you? You are getting paid, you get on with it.
********
VICTORIA
Philippa Tuckman runs the Military Claims Department at Bolt Burdon Solicitors in London.
Philippa
My client was going to be posted to Kenya in early 2012… He was given Lariam. The anti-malarials were handed out not by a doctor or by any medical staff, but on the parade ground by somebody further up the chain of command; not a medical person.
Victoria
So when he couldn’t sleep and his mood became erratic, he claims he didn’t know he should have told his medical officer and stopped taking the drug.
Philippa
He suffered what is called a Tonic Clonic Seizure, and it was unfortunately not the last. They could find no neurological cause and it was one of the neurologists who asked him whether he had ever taken anti-malarials.
Victoria
Seizures are one of the potential side effects listed in the Product Information for Lariam.
Philippa
So he has now been medically discharged from the Army. This very promising career has been lost and it looks as if there may very well be a link with the Mefloquine that he was given, not prescribed.
********
VICTORIA
In Ireland there are currently about twenty legal cases being pursued against the Government by former members of the Defence Forces. They were all prescribed Lariam for UN peacekeeping missions.
Killian Carty represents many of them.
Carty
The people that we are representing were not explicitly informed that if they went on to develop any unusual symptoms like depression or anxiety or psychotic or paranoid reactions that they should immediately go back to their doctor and tell them about it. And some people have had very acute psychiatric reactions to it.
Victoria
Such legal cases are rare.
Philippa
Soldiers are very, very reluctant to take the MoD to court. It is an issue of loyalty. The time when they will go public is normally after a great deal of very strong attempts to try to get that loyalty to go both ways.
Dannatt
One of the things that is so frustrating and makes me really very angry is that I am having to have this conversation with you, the BBC, when I have had the door slammed in my face by Ministers and the Surgeon-General’s Department.
Victoria
You simply want the Ministry of Defence to listen to people.
Dannatt
I want them to listen, I would like them to stop using it.
********
VICTORIA
Jane Casperson-Quinn has also been quietly campaigning behind the scenes.
Jane
They need to review their prescribing practices, and their risk management evaluation of drugs which are known to have significant side effects, whether those drugs be psychiatric or otherwise; and put in place some real workable surveillance and follow up procedures that allow people to report in confidence.
Victoria
We asked the Ministry of Defense to appear on this program. We had so many questions we wanted to ask them. But they declined. They gave us the following statement:
Ministry of Defense Voice:
“All our medical advice is based on the current guidelines set out by Public Health England. Based on this expert advice the Ministry of Defense continues to prescribe Mefloquine as part of the range of malaria prevention treatments recommended, which helps us to protect our personnel from this life-threatening disease.
Mefloquine is used across the UK, not just by the Military, and is only ever prescribed after an individual risk assessment. There is no defined caveat from any advisory body in the world that suggests its use should be restricted in military personnel, or people who handle weapons.”
Croft
The military go to Public Health England for their advice, which is inappropriate because they should be developing their own policies based on their own knowledge of their own working environment, not borrowing some other body’s policies that are already designed for a completely different group.
Victoria
Doctor Ashley Croft was a consultant public health physician at the Surgeon-General’s department, and a NATO public health adviser.
Croft
The MoD should take note of the science behind this problem, and the science spells out very clearly that Mefloquine/Lariam is a very dangerous drug in some users. There are safer alternatives, so the MoD should immediately stop issuing Mefloquine to soldiers; and in my view they should ask the Surgeon-General, who over a period of fifteen years has been giving them very bad advice, to resign. And if that resignation isn’t voluntary it should be made compulsory.
Victoria
So they should sack the Surgeon-General if the Surgeon-General doesn’t resign voluntarily?
Croft
Yes. Indeed, yes.
Victoria
And if they don’t do those things?
Croft
I think the inevitable result will be that there will be some terrible human tragedy in the British Army as there was in the American Army, that could have been avoided by the use of a safer drug.
Victoria
(background recording of report of incident)
The murder of sixteen Afghan civilians in Kandahar by Staff Sergeant Robert Bales in 2012 has been persistently linked to Lariam. As were a spate of killings of military wives (by their husbands) at Fort Bragg ten years earlier.
The evidence though is far from clear, but all were either in or working with US Special Forces, who have now banned the drug.
Nevin
There is no justification for this drug to be used in combat settings. The US military developed this drug but there is a very good reason why we don’t use this drug that we invented. And for our allies to ignore that fact; I think they do it at their own peril.
“The Lariam Legacy” produced by Deborah Dudgeon, a “Whistledown” production for BBC Radio 4
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