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US Agency Issues New Warnings About Anti-Malaria Drug - 2003-07-30

On July 9, the U.S. Food and Drug Administration ordered that patients who are prescribed the anti-malaria drug mefloquine, which is sold by the trade name Lariam, be warned that the drug has been linked to serious mental problems and even reports of suicide. VOA's Carolyn Weaver takes a closer look at the controversial drug, which has been a lifesaver for some, yet for others, a prescription for unintended damage.

Kristi Anderson was a federal criminal investigator when she traveled to South Africa on vacation in 1991. To protect her against malaria, a potentially fatal infection spread by mosquito bites, Ms. Anderson’s doctor prescribed a drug called mefloquine, sold in the United States under the brand name Lariam.

After the third pill, Ms. Anderson says, she began having constant dizziness, nausea, and panic attacks. “Almost always there was nausea,” she remembers, “but sometimes it was a wave of dizziness or vertigo, and then I would start having this feeling of impending doom, I wanted to get out of where I was, I just wanted to get back home or someplace where I felt safe because I was afraid something terrible might happen.”

Ms. Anderson says her nausea, anxiety and dizziness were so severe that she ultimately had to quit her job. She moved back to California to live with her parents for a year-and-a-half, until she was well enough to go back to work.

But in 1996, she returned to South Africa, again took Lariam and again became violently ill. Only then did she begin to suspect the drug was the cause. She sought a diagnosis at Stanford University’s California Ear Institute, where tests by the medical director documented injury to the part of the brain that controls balance, the vestibular system.

“He told me from the Lariam patients he had seen and what his tests showed, he believed that Lariam was the cause of my vestibular problems and he thought it was the cause of the earlier problems as well,” Ms. Anderson says.

The Roche pharmaceutical company, which makes Lariam, declined VOA’s requests for an interview before we first broadcast this story, and again last week. But in the 14 years since mefloquine was approved for use in the United States, Roche has added increasingly serious warnings of possible adverse effects in the package insert given to doctors. It’s a long list that includes, among other things, nausea, vomiting, dizziness, convulsions, depression, hallucinations, psychotic or paranoid reactions, and anxiety.

The Food and Drug Administration’s latest action orders doctors to give patients a new medication guide warning that “Lariam can rarely cause serious mental problems in some patients” and that those side effects may continue. It also says, “There have been rare reports of suicides,” but adds “we do not know if Lariam was responsible.”

Last year, Roche settled a lawsuit brought by a woman whose husband committed suicide after taking Lariam. The terms of the settlement were kept secret. More recently, the U.S. Army investigated whether the drug was implicated in several murder-suicides at the Fort Bragg army base in North Carolina last summer. Two of four soldiers who killed their wives and then committed suicide had taken Lariam. The Army’s report on the murders called a connection to Lariam unlikely, but did not exclude it.

Malaria is endemic to many parts of Africa and Asia, and kills nearly one million people a year, most of them young children. Others are damaged permanently by the disease. And so despite the new warnings, many tropical health and travel specialists, like physician Martin Wolfe, regard Lariam as an essential drug – and more practical than the alternatives doxycycline or Malarone.

In contrast to those drugs which must be taken daily, Dr. Wolfe notes, Lariam is taken only once a week. “We believe the compliance is better with a drug taken once a week than one taken daily,” he says. “And since we are protecting against a potentially life-threatening disease, we want to do the very best we can to encourage people to take their medication.”

It’s impossible to pin down the incidence, but some experts say the rate of severe reactions is far higher than the one in 10,000 cited in early research by Roche. A study published in 2001 in the journal Clinical Infectious Diseases reported “mild to serious” neuropsychiatric adverse effects in 29% of travelers on Lariam.

Retired Colonel Wilbur Milhous was among the military scientists who developed Lariam at the Walter Reed Army Institute for Medical Research and then licensed the Roche company to make and sell the drug. But as reports of severe side effects emerged, he says the government promised Roche it would continue to back the drug. “There was clearly an unmet medical need which the drug fulfilled,” Colonel Milhous says. “We were frightened from a U.S. perspective, in terms of national contingencies, what would happen if it were withdrawn?”

The U.S. Army today depends on Lariam, as does the Peace Corps, because of the once-weekly dosing. But as Colonel Milhous says, malaria researchers must always be at work on the next generation of new drugs, because the malaria parasite quickly develops resistance. The best weapon against malaria, he says, would be vaccination. Last week, tests of a new vaccine began on 2,000 children in Mozambique. Earlier trials found the vaccine, created by the SmithGlaxoKline company, safe and effective in adults, though the effects lasted only two months. Investigators hope it will remain effective longer in children.

As for Kristi Anderson, she says her recent brain scans are normal, and her other symptoms have diminished. But she says she began to heal emotionally only when she read a newspaper story about Lariam. “Reading that article released me from this shame of ‘Kristi, you’re some kind of weak person and you better watch out because you’re going to have a nervous breakdown again sometime, you just better be careful,’” she says. “I realized that’s what made me sick - that’s what happened to me, that’s why I became a different person.”

Some footage for this report provided by Reuters, ABC News and the Hospital Clinic of the University of Barcelona.