HEALTH: "Malaria Pill's Side Effects Raise Issues About Safety"
By VANESSA FUHRMANS
Staff Reporter of THE WALL STREET JOURNAL
September 4, 2002
Can a popular malaria drug trigger suicide in extreme cases?
Recent reports of Lariam's sometimes scary psychiatric side effects are bringing attention to the drug's safety and, for the first time, prompting its maker to notify doctors of a small number of reported suicides in its users.
Roche Holding AG plans to mail notices to U.S. health-care professionals, alerting them to recent changes it made to Lariam's official product information. Though the company maintains that no link has been established with the drug, it changed the label after consulting with the FDA to acknowledge "rare cases of suicidal ideation and suicide have been reported."
If symptoms of acute anxiety, depression and confusion occur, the label continues, these could lead "to a more serious event" and patients should quit the drug and take another malaria medicine.
Regulators in the United Kingdom require explicit consumer warnings. Five years ago, the U.K.'s Malaria Advisory Committee recommended restricting Lariam to travelers going to malaria regions for more than two weeks.
The revisions in the U.S. are Roche's strongest acknowledgment yet of Lariam's rare but sometimes severe side effects, including hallucinations and psychotic episodes. But they aren't likely to be the final word in the debate over the drug's safety.
Just as Roche made the changes, U.S. army investigators said last month they would examine Lariam as a factor in a series of murders and suicides by soldiers this summer at Fort Bragg, N.C.
While investigators warn that they have yet to find signs of a link, the news is raising more questions, and confusion, about the drug's potential risks.
What is clear is that Lariam, which has been prescribed to 25 million people world-wide since its introduction in 1985, is one of the most effective prevention treatments for malaria, one of the world's most deadly communicable diseases. It has saved countless lives and reduced the rate of infection dramatically in Peace Corps volunteers, U.S. military and many civilian travelers. Most have experienced only mild or no side effects. In general, malaria pills are prescribed when travelers visit places such as India, Thailand, Vietnam and countries in Africa.
But what is also known is that in rare circumstances, side effects do occur and they can sometimes be bizarre or traumatic. Some patients complain of hallucinations, nightmares, paranoia, extreme anxiety and psychotic episodes.
"The side effects of Lariam probably don't occur more frequently than they did with the old stuff, like quinine," says Ib Bygbjerg, professor of international health at the University of Copenhagen. "But when they do appear, the severity is certainly different."
After taking three Lariam tablets on a trip to the Philippines in March 1997, Bruce White, a 45-year-old civil engineer from St. Albert, Alberta, became disoriented, breaking into cold sweats and feeling like he was floating outside of his body. "I could see myself lying there with all of my intestines and everything exposed," he recalls.
By the time he checked into a local hospital, he was having full-blown hallucinations, imagining people morphing into monsters. Over the next several days, he became violent, striking out at people.
What is disputed is just how often such side effects can happen because the definition of a severe side effect is disputed. A 1993 Roche-sponsored study looking at Lariam in 145,000 travelers put the risk at one in 10,000, defining "severe" as causing death or hospitalization. A British study in 1996 of 2,395 patients looked for problems just severe enough to stop people from carrying out their daily activities and found one in 140 suffered them.
But many doctors now point to a study published last year in the journal Clinical Infectious Diseases that was the first to pit Lariam against a new treatment, Malarone, without revealing which participants got which. Of the 483 who received Lariam, 29% suffered mild to severe psychiatric side effects, compared with 14% in the Malarone group. GlaxoSmithKline PLC, which makes Malarone, sponsored the study.
It is much less clear whether there is any link between Lariam and suicide. U.S. Food and Drug Administration records contain reports over the past four years of 11 suicides of people who had taken Lariam. Both Roche and the FDA say there is no biological or statistical evidence of a connection between the suicides and Lariam.
Despite the risks, even health-care experts who have voiced concern about Lariam say it is still a needed drug. Alternatives like doxycyline can make people more sensitive to the sun and even lead to burns. While Malarone, which was FDA-approved in 2000, shows similar effectiveness to Lariam, doctors caution that long-term studies on its safety haven't yet been done. And both have to be taken once a day, compared with Lariam's once-weekly regimen. Skipping a single day can expose a person to malaria.
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Updated September 4, 2002
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