May 21, 2002 - Insight Magazine: Use of anti-malarial drug Lariam previously used by Peace Corps Volunteers linked to Mental disorders, suicide (Part I)
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May 21, 2002 - Insight Magazine: Use of anti-malarial drug Lariam previously used by Peace Corps Volunteers linked to Mental disorders, suicide (Part I)
Use of anti-malarial drug Lariam previously used by Peace Corps Volunteers linked to Mental disorders, suicide (Part I)
Read and comment on this story from Insight Magazine on mounting evidence that suggests the anti-malaria drug Lariam -- prescribed to Peace Corps volunteers, travelers and U.S. soldiers -- has triggered mental problems so severe that in a small percentage of users it has led to the ultimate side effect: suicide at:
Lariam and Suicide*
* This link was active on the date it was posted. PCOL is not responsible for broken links which may have changed.
Lariam and Suicide
By MARK BENJAMIN and DAN OLMSTED
WASHINGTON, May 21 (UPI) -- Mounting evidence suggests the anti-malaria drug Lariam -- prescribed to Peace Corps volunteers, travelers and U.S. soldiers -- has triggered mental problems so severe that in a small percentage of users it has led to the ultimate side effect: suicide.
Lariam -- also known as mefloquine -- is a product of Hoffmann-La Roche, a giant Swiss pharmaceutical company with U.S. headquarters in Nutley, N.J. Lariam has been prescribed to more than 22 million people worldwide since 1985. It was cleared for use in the United States in 1989.
Some health experts charge that neither patients nor doctors in the United States are being adequately warned about the risk of suicide from taking Lariam, which is prescribed by U.S. doctors 1,000 times every day.
In a two-month investigation, United Press International reporters found:
* In thousands of pages of internal Roche documents obtained by UPI spanning a decade, the company tracks increasing reports of suicides, suicidal behavior and other mental problems among Lariam users.
* A 1994 Roche safety report notes that because Lariam can cause depression and depression can lead to suicide, "a causal link to Lariam can in theory not be ruled out."
* Dozens of soldiers, Peace Corps volunteers, other government workers and private travelers, in interviews with UPI, court filings, case studies and reports from medical personnel, said they had no history of mental illness before taking Lariam, but then attempted or considered suicide. Families gave similar accounts of several who succeeded in killing themselves.
* An activist group said it has heard from 120 Somalia veterans who had problems they attributed to Lariam, including suicide attempts. Military medical officers in charge of giving Lariam to more than 20,000 U.S. troops there in 1992 and 1993 said they saw no evidence of a problem. Troops in Afghanistan are taking Lariam as the weather warms, but some officers on the ground in Afghanistan said they themselves were not taking it because they feared liver damage.
* The U.S. Food and Drug Administration's files contain reports over the past four years alone of 11 suicides, 12 suicide attempts, 41 cases of thinking about suicide and 144 cases of depression among Lariam users.
* A statistical analysis of FDA data, commissioned by UPI, indicates that Lariam users are five times more likely to report having mental problems that could lead to suicide than those taking a different drug -- the antibiotic doxycycline -- also used to prevent malaria.
* More than a dozen lawsuits over the alleged effects of Lariam have been filed in the United States -- at least seven against Roche, and the others against doctors or pharmacists. Some have been dismissed or settled out of court.
"There have been a number of cases of suicide, both in the United States and abroad, that are clearly associated with the use of Lariam," said Susan Rose, an adjunct assistant professor at George Washington University's public health school and an attorney who has represented plaintiffs suing Roche.
No one has won a case against Roche alleging Lariam caused a suicide, but Rose, speaking as an advocate for plaintiffs with a background in public health, said: "Suicidal thoughts and impulses are far more commonly experienced than the current product information sheet would lead physicians or consumers to believe. This is critical, life-saving information that must be conveyed now to travelers and the medical community."
Roche consistently has denied there is evidence showing taking Lariam can cause the kinds of mental problems that could lead to suicide. The company said Lariam is an important drug for combating malaria.
"Believe me, as a company we support this drug and stand behind it," said Roche spokesman Charles Alfaro. "Roche works with all regulatory authorities both before and after product approval to ensure recommendations for product use that take into account current medical evidence."
"It (Lariam) remains a drug of choice for the prevention and treatment of malaria by such leading health authorities as the CDC (Centers for Disease Control and Prevention), the WHO (World Health Organization) as well as many travel organizations, clinics, and individual physicians," Alfaro said.
Asked whether Lariam could cause suicide, Alfaro said he could not answer because it was an issue in pending litigation.
Adverse side effects of drugs are voluntarily reported by physicians and others to the FDA and drug companies. The FDA said in general, drug side effects are reported in only 1 percent to 10 percent of cases.
Dr. Raymond Woosley, dean of the University of Arizona Medical School and an expert on drug side effects, said he would be "very comfortable" with an estimate of actual suicides 100 times greater than the 11 reported to the FDA in the past four years.
Experts said the FDA lacks the resources to follow up on side effect reports even for drugs recently approved.
"I would be very surprised if there's very much surveillance of this drug (Lariam) at all," said Woosley. "It's 12 years old. The FDA probably wouldn't have the people power. They're understaffed, they have inadequate resources and they're putting out fires and looking at new drugs."
The FDA said in a written statement to UPI it would have taken action if it had confirmation Lariam caused suicide. But the FDA said confirmation required either biological or statistical evidence.
While the FDA database included reports of 11 suicides among Lariam users, all but one of them outside the United States, the agency said "to 'blame' Lariam for all these cases is not scientifically justified."
"On balance we believe the risk of such rare and poorly substantiated events is more than offset by the benefit in preventing malaria deaths," the FDA statement said.
Under the "less frequently reported adverse events" section on Lariam's label, Roche added in 1999: "Suicidal ideation (thinking) has also rarely been reported, but no relationship to drug administration has been established." These labels in the United States come as fine-print package inserts that patients do not automatically receive.
Other nations have acted to ensure consumers receive warnings of possible adverse reactions to Lariam --which is chemically related to the quinolone group of antibiotics, long documented as capable of causing mental problems.
In 1997, the British Malaria Advisory Committee, for instance, stopped recommending Lariam for trips of two weeks or less. Patients who do take it receive a written warning that includes: "Effects on nervous system: psychiatric reactions which may be disabling and last for more than several weeks. These include unusual changes in mood or behavior, feelings of worry or anxiety, depression, feelings of persecution, crying, aggression, restlessness, forgetfulness, agitation, confusion, panic and hallucinations. If you experience any of these effects you should immediately stop taking Lariam and consult a doctor."
In Canada, "Information for the Consumer" from Roche states: "It is best to avoid alcoholic drinks during treatment with Lariam." No such warning appears on the U.S. label despite increasing concerns alcohol can be a problem when mixed with Lariam.
"I think alcohol, in particular, can be a confounder with Lariam," said Dr. Alan Magill, a Walter Reed Army Medical Center official who was in charge of the health of U.S. soldiers deployed to Somalia in the early 1990s.
Magill said he saw no major side effects among troops taking Lariam. By contrast, Jeanne Lese, information manager of the activist group Lariam Action, said "more than 120 Somalia vets have contacted us about Lariam and 11 said they have considered or tried suicide -- one tried it 10 times and shot herself twice" but survived.
UPI interviewed half a dozen of the Somalia veterans who had contacted the group. They spoke of marked personality changes in themselves and others, suicidal thoughts and suicide attempts, flashbacks, nightmares and paranoia. One said that most soldiers drank alcohol daily, aggravating the side effects. Another said his doctor in the United States did not seem aware of Lariam side effects.
The CDC declared Lariam its "drug of choice" in March 1990 and that fall recommended doses of Lariam be doubled from once every two weeks to once a week, after the first four weeks of weekly doses. Because the CDC is the guidepost for malaria prevention in the United States, other government agencies, private travel clinics and doctors quickly adopted the regimen.
That recommendation followed a survey of 562 Peace Corps volunteers, led by the CDC's chief malaria expert, Dr. Hans Lobel. The study results eventually appeared in the Journal of the American Medical Association in January 1991.
"No serious adverse reactions were observed," Lobel wrote of the volunteers who took Lariam. Because some of those volunteers contracted malaria, a sometimes-deadly disease, Lobel said weekly doses of Lariam "should be considered."
Some doctors said the U.S. government never should have used the Peace Corps study as a basis for increasing doses of Lariam.
The dose increase was "an astonishing piece of non-evidence-based science," said Dr. Ashley Croft, a British army lieutenant colonel who has done extensive research on Lariam and who said he believes it can cause serious mental problems that increase as doses rise.
"It is really quite amazing that this doubling-the-dose policy - which of course doubled the company's profits at a stroke - was immediately adopted everywhere, and on the basis of such a flawed study," Croft said.
He said he believes that in the Peace Corps study, some of the volunteers may have quit taking the drug because it bothered them, and got malaria as a result.
In a 1994 internal Roche document, the company said an evaluation by Lobel, director of the CDC's malaria prevention program at the time, indicated the Lariam package insert was adequate.
"According to a consultant expert in the field of malaria, Dr. H. Lobel, CDC, Atlanta, the current package insert adequately addresses suicidal ideation under 'depression', in view of the isolated reports received," the 1994 Roche safety report read. "No change in the package insert is required at present."
Roche declined to discuss Lobel's recommendation with UPI or his status in the 1994 report, which called him a consultant expert. CDC rules prohibit compensated or uncompensated consulting without express written permission.
CDC spokesman Tom Skinner said the agency does not have records indicating Lobel received such permission, if it was needed.
"I have never been a consultant for Roche," Lobel told UPI. He did say he often worked as a consultant for other organizations, such as the World Health Organization, but not for Roche.
Skinner said the CDC had opened an ethics inquiry in the issue. "There is a formal process the CDC must go through to determine if any action needs to be taken," Skinner said.
UPI reviewed thousands of pages of Roche's internal safety reports for the decade after the drug dose was increased. "Eight patients attempted suicide, three by leaping out a window," reads one Roche safety report of side effects documented through 1993, in a section titled "Depression with Suicidal Tendency."
A 1994 safety report said because Lariam can cause depression and depression can lead to suicide, "therefore a causal link to Lariam can in theory not be ruled out." It went on to say reports of suicide attempts were rare and fell within the incidence of suicides among the general population.
That document also noted "the first report of suicide with the use of Lariam" and went on to say "Roche has received eight reports of attempted suicide, four of them associated with depression (previous (medical) history unknown)."
"Fourteen additional patients reported suicidal thoughts. All were associated with psychiatric disturbances" including depression, the 1994 report said.
That first report of suicide in 1994 was of Canadian Army Cpl. Scott Smith, who was stationed with the United Nations in Rwanda. Smith reported having hallucinations he attributed to Lariam months before his death.
In an October 1994 interview with a journalist on a flight from Somalia to Rwanda, Smith said the difficulties began when he was stationed in Somalia. The writer, a correspondent for Canadian Transportation Logistics, reported the conversation in the December 1994 edition of the magazine. It appeared shortly before Smith's death.
"Cpl. Scott Smith ... is one of the unfortunate ones to react to the malaria medicine everyone has to take. He experiences hallucinations," the magazine said.
The Roche safety report on Smith made no mention of the reported hallucinations and said use of Lariam was "more likely coincidental" to the suicide, especially since Smith had been drinking.
A Roche safety report for 1998 -- the last year examined by UPI -- said of Smith: "There is insufficient information for assessment of this case. The Canadian military has not confirmed this information nor have they provided any clarification. All information has been compiled from the media," it said.
Canadian Member of Parliament John Cummins studied reports of Lariam side effects among Canadian soldiers. Cummins said Roche should have known and stated in its report that Smith had hallucinations he attributed to Lariam.
"I think that is gross negligence on their part," Cummins told UPI.
But Cmdr. David Carpenter, head of the Canadian military's communicable disease control section, said Lariam remains the drug of choice "where indicated" by the kind of malaria and whether the disease is resistant to other drugs. Asked about the Smith case, Carpenter told UPI, "I vaguely have heard of it," but he said a government review found "there was nothing to substantiate it was mefloquine-related."
He said Lariam's rare psychiatric side effects are well-known and troops are carefully monitored for bad reactions, in which case they are generally given doxycycline. But he said, "When you're doing travel medicine for the military as I do, you have to weigh the real and often very common risk of getting malaria against the risk of psychiatric problems. Usually the balance is toward preventing malaria."
The 1994 Roche safety report also attributed suicidal tendencies chiefly to factors such as "the progressive break down of traditional values" and family structure, substance abuse and unemployment, not to Lariam use.
By 1998, Roche reported that four suicides during the year might be connected to Lariam, but said, "No causal relationship could be established." That year, it added a new appendix to the annual safety report entitled, "Special Review: Lariam and Suicide, Suicide Attempt and Suicidal Ideation" (thinking about suicide). The report said the company was tracking seven suicides, 13 suicide attempts, 46 cases of thinking about suicide and 3,419 "psychiatric events."
(to be continued in Part II of this story)
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