May 21, 2002 - Insight Magazine: Use of anti-malarial drug Lariam previously used by Peace Corps Volunteers linked to Mental disorders, suicide (Part II)

Peace Corps Online: Peace Corps News: Library: Peace Corps: Lariam : Discussion of the Use of anti-malarial drug Lariam: Archive of Stories: May 21, 2002 - Insight Magazine: Use of anti-malarial drug Lariam previously used by Peace Corps Volunteers linked to Mental disorders, suicide (Part II)

By Admin1 (admin) on Wednesday, May 29, 2002 - 1:02 pm: Edit Post

Use of anti-malarial drug Lariam previously used by Peace Corps Volunteers linked to Mental disorders, suicide (Part II)

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*

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Lariam and Suicide


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.

For the men and women troubled by Lariam, those dry statistics were very real and sometimes deadly experiences.

"I was a raving, crazy lunatic," Martin Giannini said in an April telephone interview with UPI from Dublin, where he is trying to rebuild a life he says was shattered by Lariam. He took Lariam from June 1995 through September 1996 as a Peace Corps volunteer while in Togo in West Africa.

He said his mental problems started with nightmares, headaches and dizziness. He said his condition the next two months quickly deteriorated into an enveloping psychosis that required him to be evacuated.

"I just went to pieces," Giannini said. "I'd been telling (Peace Corps medical personnel) since Day One that I had been having problems with this drug."

Back in the United States, Giannini suffered from hallucinations. He heard voices. His mental problems climaxed in a three-day high-speed car trip that led him from Oklahoma to Illinois and into Wisconsin, where after a car crash he was found wandering in the woods. He has been hospitalized several times. He said he considered suicide.

"There were times ... It was amazing I survived."

Peace Corps medical officials said reports of mental problems among volunteers are due to the onset of schizophrenia that can show itself in the early 20s, when most volunteers join up, but not because of Lariam.

"We do get people who develop schizophrenia in the Peace Corps, but it is not associated with mefloquine," said Russell Gerber, chief of the epidemiology unit at the Peace Corps.

Giannini sought back wages from the U.S. government, because the Peace Corps is a federal agency. In March 1998, the U.S. Department of Labor wrote Giannini a letter saying the department agreed to pay his medical expenses and compensate him for lost wages, "for a single, sustained, but acute psychotic reaction to mefloquine use" that lasted a full year.

UPI talked to 32 doctors, scientists and other experts, and 27 people who said they suffered adverse side effects from Lariam use. UPI reporters also reviewed dozens of e-mails from around the world -- from soldiers, travelers and medical experts in the field -- about problems with Lariam, as well as published reports.

Some examples:

-- Francis Macleod Matthews, a 37-year-old lawyer who had taken Lariam a year earlier but continued to be troubled by bad dreams, threw himself off the roof of an apartment building in London. The coroner, Paul Knapman, ruled the death a suicide and said, "It is more likely than not that Lariam played some part," according to the Times of London.

-- Irish tourist Malcolm Edge, 27, was found hanging in a hotel room in Ho Chi Minh City, Vietnam, in 2000; he was taking Lariam. Edge had undergone a startling personality change on the trip, according to a traveling companion. The Dublin coroner notified the Irish Medicines Board that "concerns were expressed at the inquest in relation to possible psychotic reactions to Lariam," but the coroner made no conclusion whether Lariam was a contributing factor in the death.

-- In Australia, John O'Callaghan, 29, committed suicide after being treated with Lariam for malaria he contracted on a surfing trip to Indonesia. "Almost immediately," his mother Jan wrote in an e-mail to the group Lariam Action, "he suffered severe neuropsychological and physical side effects. We did not know he was suffering from mefloquine toxicity. He had no history of these (physical and mental) illnesses. For a couple of years he tried to return to his previous healthy lifestyle. Finally, in September 2000, he took his own life." He left a note:

"I know God will forgive me. No one could live with how I am feeling now. I know I will never forgive the bastards that gave me Larium. I am now the same as when I first had it -- fully spinning can't even walk properly - the walls are moving. My head feels like someone let a box of ants in it, extreme pain in my head. I am fully losing it. What does the future hold -- 'psyciatric wards' no way. I know I've always been a little bit different even before I had Larium but since it first blew my brains apart and then settled down I have never been the same, always dazed and confused, always physically sick. I never thought this could happen to me. Sorry Mum, Dad"

O'Callaghan's account of symptoms mirrors those of several others: Charles Perry, who committed suicide in Ohio in 1999, spoke of a relentless pain at the base of his cranium, said his wife, Linda: He would put his head on the table and hold his hand over the base of his skull, saying, "This is where it hurts." (Linda Perry sued Roche for alleged failure to warn about side effects, including suicide. The lawsuit recently was settled out of court. The terms were not disclosed).

Rosemary Waller of Cincinnati kept a diary of symptoms that developed after she took Lariam in the summer of 1997. Her entry for May 3, 1999, reads: "Scalp burning, gripping intensified into worst-ever headache." On June 8 she noted "almost continuous scalp sensations of burning, crawling, gripping, hole-boring through in one of several spots on scalp."

Elisa von Joeden-Forgey, who went to Africa in 1995 as part of her doctoral work at the University of Pennsylvania, described "this horrible burning sensation in the back of my head, in my lower cranium, this burning, constant burning."

-- In a March e-mail from Nairobi, Kenya, psychiatrist Dr. Lorin Mimless wrote of treating seven patients with what he said were clear Lariam reactions.

Among the cases he describes is a 32-year-old man he saw a year ago who he said had no history of psychiatric problems and was on no other medicine. He said the man became paranoid and over a two-day period his problems "developed into a full-blown psychosis requiring hospitalization in Britain. The patient on arrival tried to kill himself by hanging."

Mimless said he saw the man recently and "he still had significant psychiatric symptoms -- depression, occasional paranoid thoughts when anxious, and suicidal thoughts that would come and go not connected to the depression. He could not explain them but they would come once or twice a month, sometimes for a day, sometimes for a few hours. He would attribute them to Lariam, although he always had the fear they would not go away."

A researcher who formerly reviewed Lariam side-effect reports at Roche said he now believes the company has been too hesitant to alert physicians and consumers to side effects that emerged after a drug had been approved.

"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," said Dr. Donald H. Marks, former associate director of clinical research at Roche. Marks said he left Roche in 1991 to take a promotion to director at another company.

Marks said there is "ample reason" to believe Lariam causes suicide. Marks said Lariam can cause "spontaneous neurological activity" and "irritation of certain sensitive areas inside the brain" that could lead to suicidal behavior long after someone stops taking it.

Roche did not respond to UPI's written questions about Marks' comments. Alfaro, the Roche spokesman, said: "Roche takes the issue of safety very seriously and is diligent in monitoring the safety of all its drugs."

Two statistical studies of FDA data commissioned by UPI showed a far higher incidence of problems that could lead to suicide in people taking Lariam than in those taking doxycycline, an antibiotic recommended by the CDC as another drug to prevent malaria.

The studies' authors said that because both drugs are recommended by the CDC for prevention of malaria, a comparison of reported mental problems among users of both drugs is valid.

The FDA said in a statement to UPI that suicide rates of patients taking doxycycline and Lariam cannot be validly compared because most people treated with doxycycline receive it for acute bacterial infection -- a much shorter therapeutic regime -- and not for prevention of malaria.

The FDA also said doxycycline has its own drawbacks: it cannot be used in children, sensitizes people to the sun, has to be taken daily while Lariam is taken weekly, and causes anorexia, nausea and vomiting.

Doxycycline is the malaria preventive President Clinton was prescribed when he traveled to India and Pakistan in early 2000.

PharmaGenesis of Bethesda, Md., and Fibonacci Group, a Philadelphia-based consulting group, conducted two separate studies of FDA raw data. Both firms do work with attorneys suing drug companies.

In one study for UPI, PharmaGenesis determined people taking Lariam were five times more likely to have reported mental problems that could lead to suicide than people taking doxycycline. In the other, Fibonacci examined the FDA data and calculated the rate of side effects per prescription. It found a 150 times greater rate of depression and a 40 times greater rate of suicide attempts among Lariam users compared with doxycycline users.

The studies did not find a single successful suicide associated with doxycycline in the past four years, even though doxycycline, an antibiotic, is prescribed 25 times more often than Lariam, which is used only for treatment and prevention of malaria. Lariam is prescribed some 350,000 times a year, doxycycline is prescribed 9 million times a year for a variety of medical reasons, according to data from IMS Health, a healthcare information company.

Experts on drug side effects warned the FDA's data cannot solely be used to draw conclusions about drug safety, but they agreed analyses from 1997 forward are best because at that point the agency began tracking suicides.

The PharmaGenesis analysis found three reports involving suicide prior to 1997 were "high probability," based on a review of the psychiatric side effects reported in those patients.

Roche's documents said seven suicides were reported by the end of 1998 as associated with Lariam use, including one in 1994, two in 1997 and four in 1998.

Roche and Lobel have said mental problems in those taking Lariam might be related to increased stress during travel. Keith Altman of Fibonacci Group said he thinks the 1997-2001 data debunk that assertion -- particularly considering the different prescription totals for the two drugs.

"If you're looking at rates-per-prescription, you're talking about a 40 times greater rate of suicide attempts in Lariam than in doxycycline," Altman said. "Look at depression: the rate of depression is 150 times greater in Lariam. I just can't see a 150-times-greater rate of depression when you consider that a lot of these people are happy they're going on a trip."

A clinical study in October 2001 in the peer-reviewed Clinical Infectious Diseases journal showed 29 percent of travelers taking Lariam complained of neuropsychiatric side effects and that 5 percent were so bothered they quit taking the drug altogether. The "randomized controlled trial" was done among 976 travelers in the field.

Another drug company, Glaxo-Wellcome, funded the study and used Lariam as a control pill to gauge the safety of its own anti-malaria drug, Malarone, approved by the FDA in July 2000. FDA data shows two suicides reported among Malarone users.

Croft, the British army lieutenant colonel, said the Glaxo-Wellcome study shows the U.S. government warnings for Lariam "need to be revised urgently now that there is good evidence for the potential harms of mefloquine."

Roche also makes Accutane, the popular acne drug that has also been associated with reports of suicide mainly among young people. In one high-profile case in Florida, the mother of Charles Bishop filed suit against Roche April 16, alleging Accutane made Bishop, 15, fly a Cessna plane into a Tampa high-rise and kill himself in January.

Roche and some drug experts have both said there is no concrete scientific evidence to link Accutane to suicide. Unlike its approach with Lariam, however, Roche in May 2000 put new language on the Accutane label warning of suicide risks, almost 20 years after the FDA approved the drug in 1982.

An alleged failure by Roche to provide adequate warning of Lariam side effects, including suicide, was at the heart of the lawsuit filed by Linda Perry in federal court in Ohio. The suit recently was settled. Charles Perry, 54 and a father of seven with no history of mental illness, took Lariam in 1998 during an African safari to celebrate his 30th wedding anniversary with his wife, Linda, a nurse.

The suit alleged the information provided by the pharmacy that filled their Lariam prescription warned only of possible "nausea, diarrhea, stomach upset, vomiting, dizziness or vision problems" and to "report difficulty breathing."

Linda Perry contended that before her husband took the fourth pill, he was hallucinating. She said after returning to Ohio, they followed directions and took another four pills over the next four weeks. But Charles Perry spiraled into psychosis. He was hospitalized in the weeks before he killed himself with a shotgun in January 1999. His psychiatrist filed a report with the FDA blaming the suicide on Lariam.

Roche contended in court that there was nothing to prove Lariam can cause suicide. "The proposition advanced by plaintiff here -- that Lariam causes such profound psychotic episodes that suicide is a known or knowable consequence of Lariam use -- is simply not supported by competent medical and scientific literature," Roche lawyers wrote in a court filing in January.

"No well-controlled clinical study supports such a causal relationship. As such, it is not generally accepted in the medical community that Lariam use leads to suicide."

But Perry's widow contends there is a connection. She said they would have stopped taking Lariam if they had been clearly warned of the risks. In an interview in the months after her husband's death, she said: "There was absolutely nothing on the bottle, from the pharmacy or from the health department that would have indicated that we should stop taking this."

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By Anonymous ( - on Saturday, May 27, 2006 - 12:07 am: Edit Post

I came across this while searching to find out if doxyclyline could cause mania / "crazy" feelings. It's hard to explain but when I take it, later feel a mania like feeling, out of control anger, thoughts and feelings. Very unusual and out of the ordinary for me. I don't know the relationship between Larium and doxyclyine but I can say for sure I don't feel right at all when taking doxycycline. It's frustrating and confusing because I have to stop taking it. The unusual thoughts and feelings scare me!

By Anonymous ( - on Wednesday, August 08, 2007 - 11:28 pm: Edit Post

I was taking tetracycline for about 11 months then switched for the last month or so to doxycycline. I have felt many of the same side effects as you and others, including: lots of gas, almost constant fatigue, frequent nausea, and recently I think depression/higher irritability due to, I think, the doxycycline. Recently, sometimes I get very angry/irritated about small things and I dont think this is normal.

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