October 24, 2002 - The Guardian: The Guardian says Lariam is not a benign drug
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October 24, 2002 - The Guardian: The Guardian says Lariam is not a benign drug
The Guardian says Lariam is not a benign drug
Read and comment on this investigative story from The Guardian on the anti-malarial drug Lariam which is used by thousands every year (including many Peace Corps volunteers in Africa), most without any problems. But some claim it causes serious side effects, ranging from depression to suicidal - or even homicidal - impulses.
One of the ironies of the current inquiry into the deaths at Fort Bragg is that mefloquine was originally developed by US Army scientists in 1971. Walter Reed passed the compound to Roche for development and with the help of the World Health Organisation trials were carried out on 562 Peace Corps volunteers. That study - led by Hans Lobel, a medical epidemiologist at the US Centers for Disease Control - observed "no serious adverse reactions".Read the story at:
'It's not a benign drug - it has ruined my life'*
* This link was active on the date it was posted. PCOL is not responsible for broken links which may have changed.
'It's not a benign drug - it has ruined my life'
Thousands take the anti-malarial drug Lariam every year, most without any problems. But some claim it causes serious side effects, ranging from depression to suicidal - or even homicidal - impulses. So should it be banned? Mark Honigsbaum investigates
Thursday October 24, 2002
On Friday August 23 - a week after the discovery of the bodies of Holly Wells and Jessica Chapman in Suffolk - police on the other side of the country received a call that a 22-year-old student had gone missing from her home in Sketty, a suburb of Swansea. Unfortunately, by the time South Wales police located Vanessa Brunt, lying unconscious in undergrowth a few yards from her home, it was too late. Depressed by a two-year battle with mental illness that had forced her to abandon her law studies at Cambridge, she had apparently taken an overdose of pills and died in hospital a few hours later.
If that was all there was to Brunt's short life and tragic death it would not warrant further comment, being simply a footnote to a summer of parental anguish. But drugs campaigners and doctors argue that, unlike Holly Wells and Jessica Chapman, Brunt's death might have been avoided. Indeed, they claim that if Hoffmann-LaRoche had taken their concerns about the severe psychiatric side effects associated with its anti-malaria medication, Lariam, more seriously seven years ago, Brunt mightnow be enjoying a brilliant career at Cambridge. According to Vanessa's parents, it was their daughter's experience with Lariam during her gap year abroad in south-east Asia in 1999 that started her on a downward spiral.
"We are in no doubt that the tablets caused the illness - Vanessa became physically and mentally ill within weeks of taking them," says her father, Michael Brunt.
If the anti-Lariam campaigners are right, the Brunts' experience is far from unique. In the past five years there has been an increasing number of reports of suicide and suicide ideation (thinking about suicide) involving western tourists who took Lariam during trips to malarial hot zones. Last year Irish student Malcolm Edge, 27, was found hanging in a hotel room in Vietnam after suffering a paranoia attack apparently brought on by a combination of Lariam and alcohol. And in April 1998, barrister Francis Macleod Matthews jumped to his death from a block of flats in Westminster in London after being unable to rid himself of bad dreams and feelings of anxiety that had plagued him since a trip to Kenya the previous September; he had been taking Lariam.
Now there is growing suspicion that psychiatric reactions to the drug may lie behind a series of killings at a US army base at Fort Bragg, North Carolina. In a three-week period this summer, four soldiers recently returned from tours of duty in Afghanistan allegedly murdered their wives then, in two cases, turned their guns on themselves. Although US army epidemiologists say they are perplexed by the killings, drug campaigners point out that three of the soldiers had been taking Lariam and had reportedly experienced dramatic mood changes that coincided with the administration of the weekly anti-malaria pill. In the case of Master Sergeant William Wright, a special operations officer who had been taking Lariam on and off for 10 years, family and friends noticed that after his return from Afghanistan he became prone to sudden rages and silences. Wright, who was jailed in July on suspicion of murdering his wife, is now said to be in a psychotic state.
"His thoughts aren't clear," says John Lown, a friend and former Green Beret medic, who visited Wright in prison last month. "He has a strange stare and talks in circles. There's something really messed up [about him]."
That is a verdict with which many doctors and clinicians who have made detailed studies of side effects associated with mefloquine - to give the drug its proper pharmaceutical name - would concur. When Roche first began to market mefloquine worldwide 11 years ago, the company acknowledged that it could have "serious" side effects in about one case in 10,000. But the studies on which the Swiss drug giant relied defined "serious" as those effects leading to long-term hospitalisation or death. As Lariam has been more widely prescribed and doctors have been able to observe people'sreactions to the drug more closely, the definition of what constitutes a serious side effect has expanded, along with the period during which it is thought these adverse effects may persist.
Andrew Bryce, the 35-year-old former director of a computer systems company in Dublin, has not been able to work since taking Lariam on his honeymoon in Kenya six years ago. Within weeks of returning to Dublin, Bryce - who had no previous history of illness - suffered what he describes as a "complete systems collapse". His symptoms included dizziness, fatigue, anxiety and nausea and his vestibular nerve - the part of the brain that controls balance - has now been permanently damaged. Although the current Lariam data sheet lists vestibular disorders as a potential side effect, in 1996 Roche warned only of dizziness, vertigo and a "disturbed sense of balance" - side effects which the company said could last for "several weeks", not years.
"I was perfectly healthy until I took Lariam," says Bryce, who is suing Roche for damages and loss of earnings. "As far as I am concerned this is not a benign drug - it has ruined my life."
Bryce's experience may be unusual but studies suggest that he is not alone. A 1996 paper in the British Medical Journal estimated that one in 150 people risked serious side effects - defined as anything that could disrupt a person's ability to carry out a daily activity - while a study last year comparing Lariam with a new, better tolerated anti-malaria medication, Malarone, put the risk of adverse side-effects ranging from insomnia and mild hallucinations, to dizziness, anxiety, depression and paranoia, at one in three. Now a new study suggests that these side effects, known as the mefloquine syndrome, may be caused by a previous history of liver damage or thyroid abnormality.
British people who claim to be victims of Lariam point out that when they formed an action group to voice their concerns about the long-term side effects seven years ago, Roche accused them of "hype and hysteria" and used the threat of legal action to silence them. But following Roche's decision last month to alter the information on its US data sheets to acknowledge that "rare cases of suicide ideation and suicide have been reported", doctors and drug campaigners feel vindicated - though it gives them little joy.
"This shows that patients were right and that the so-called experts and drug company were wrong," says Lance Cole, co-founder and chairman of the now defunct Lariam Action Group. "Meanwhile, the suffering of Lariam victims continues."
The issue, according to campaigners, is not whether Lariam should continue to be prescribed. Malaria is one of the world's deadliest parasitic diseases and most people who take the drug experience only mild side effects, or none at all. Rather, it is whether Roche could have made doctors and patients aware of all of the risks sooner. Even now the product information in the US is different to the information given in the UK. While the current US data sheet warns that psychiatric symptoms may continue "long after" Lariam has been stopped, the UK data sheet refers only to "suicide tendencies" and warns that psychiatric reactions may last "for more than several weeks".
"If Roche are saying suicide has been reported in the US why aren't they also saying it here?" asks Peter Barrett, the senior medical adviser for the Medical Advisory Service for Travellers Abroad (Masta) and one of the authors of the 1996 study in the BMJ. "To suggest that American citizens have different reactions to British ones is patently absurd."
But are the concerns about suicide overblown? Studies show that people who travel abroad are at a higher risk of suicide than those who stay at home, regardless of whether they have taken Lariam or not, and Roche points out that so far "no relationship to drug administration has been confirmed". Having said that, Lariam can induce vivid hallucinations - when I was in the Venezuelan Amazon researching a book on malaria I dreamed I was being attacked by a giant rat and a friend told me he thought he was being eaten by a chicken.
Research suggests that most people will survive these episodes. But for a small minority Lariam may tip them into a psychosis from which they never recover. As John O'Callaghan, a 29-year-old Australian who became mentally ill after taking Lariam during a surfing trip to Indonesia, wrote in a suicide note two years ago: "Since [Lariam] first blew my brains apart... I have never been the same, always dazed and confused, always physically sick. I never thought this could happen to me. Sorry mum, dad."
One of the ironies of the current inquiry into the deaths at Fort Bragg is that mefloquine was originally developed by US Army scientists in 1971. Then, as now, pharmacologists at the Walter Reed Army Institute of Research in Maryland were at the forefront of anti-malaria research because of the threat the disease posed to US troops fighting in the tropics. When strains of malaria resistant to chloroquine started to appear in Cambodia and Vietnam, the army scientists began looking for alternatives. Mefloquine - a synthetic relative of quinine, the oldest known anti-malarial - seemed the answer to their hopes.
Walter Reed passed the compound to Roche for development and with the help of the World Health Organisation trials were carried out on 562 Peace Corps volunteers. That study - led by Hans Lobel, a medical epidemiologist at the US Centers for Disease Control - observed "no serious adverse reactions". Indeed, in 1991, Lobel argued that because of the threat posed by malaria, weekly doses of Lariam should become standard and the drug was quickly adopted as the prophylactic of choice by the US government and army.
In the same year, Lariam was approved for use in the UK and in 1995 the UK Malaria Advisory Committee felt confident in recommending it to doctors as the prophylactic of choice for travellers to areas of high malaria transmission. Roche's data sheets at the time acknowledged that "psychotic manifestations" including "anxiety and depression" might be unwanted side effects but stressed that these symptoms were no worse than those of the disease itself. However, it has since emerged that the company was already tracking reports of suicidal behaviour and actual suicide. In an internal company safety report from 1993, obtained by the news agency United Press International (UPI), Roche documented eight suicide attempts and "the first report of suicide with Lariam". The following year, in 1994, another safety report recognised that because Lariam can cause depression and depression can lead to suicide "a causal link to Lariam can in theory not be ruled out."
Then, between 1997 and 2001, the US Food and Drug Administration (FDA) documented 11 suicides and 12 suicide attempts associated with Lariam. A former clinical researcher at Roche, Donald H Marks, concluded that the company had been too hesitant in alerting doctors and patients to the side effects."Roche has developed an attitude of not adjusting the information it supplies to physicians and patients about the performance and safety characteristics of their drugs," Marks told UPI.
Roche UK said it could not comment on these claims without more details but said that in general it took safety issues "very seriously" and worked closely with regulatory authorities to ensure that recommendations on product use took into account "current scientific and medical evidence". It pointed out that the recent changes to the US data sheet had been made in conjunction with the FDA and that "different regulatory authorities have... different requirements on wording."
However, Roche's explanations do not impress anti-Lariam campaigners. Cole points out that the WHO first reported the association between the drug and adverse events lasting "four or more months" in 1992. The same year the UN banned mefloquine for peacekeeping troops in Cambodia because of concern about the drug's "neuropsychiatric side effects... in military personnel".
Similar concerns about the impact the drug could have on people who carry responsibility for others' lives led the civil aviation authority to ban Lariam for flight crews in 1995. And following shooting incidents involving British paratroopers on Lariam in Sierra Leone two years ago, the British army now prefers to issue chloroquine and proguanil, while the Australian army issues an antibiotic, doxycycline.
Paul Clarke, the director of Masta and co-author with Barrett of the 1996 BMJ study, argues that Roche's decision to change its US data sheet vindicates their findings. "It is impossible for me to say what caused these recent suicides in the US and Britain but given the coincidence in timing with the [administration] of Lariam I would say the possibility cannot be ruled out," says Clarke.
Nevertheless, Barrett sees no reason why Lariam should not continue to be prescribed, as long as preventive treatment begins at least three weeks before travelling. The reason is that if you are one of the unlucky minority who react adversely to Lariam the side effects should be apparent by the fourth dose. "In our view it is better to discover that before you leave home and switch to another medication rather than risk falling ill abroad," says Barrett.
But while this advice may reassure travellers who are planning a trip to Africa or the far east this winter, it is unlikely to be much comfort to the Brunts. In a press statement before their daughter's funeral, the family said that although Vanessa had shown signs of recovering from her illness, during a visit to her mother's family in Paris in June she had had a severe relapse and was admitted to hospital. "Vanessa had wonderful potential but sadly that will never now be realised. We are heartbroken," said her father.
· Mark Honigsbaum is the author of The Fever Trail: In Search of the Cure for Malaria (Macmillan); the paperback will be published on November 8. For further information, email: LariamInfo@earthlink.net.
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