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Lariam

Mefloquine is an orally administered antimalarial drug used as a prophylaxis against and treatment for malaria. It also goes by the trade name Lariam^TM (manufactured by Roche Pharmaceuticals) and chemical name mefloquine hydrochloride (forumulated with HCl). Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research in the U.S. as a chemical synthetic similar to quinine. more...

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Side-effects

Like many other drugs, mefloquine has adverse side-effects. It is known to cause severe depression, anxiety, paranoia, nightmares, insomnia, vestibular (balance) damage and central nervous system problems. For a complete list of adverse physical and psychological effects — including suicidal ideation — see the most recent product information. In 2002 the word "suicide" was added to the official product label, though proof of causation has not been established. Since 2003, the FDA has required that patients be screened before mefloquine is prescribed. Anyone taking antidepressants or with a history of psychiatric illness should not take mefloquine. The latest Consumer Medication Guide to Lariam has more complete information.

In the 1990s there were reports in the media that the drug may have played a role in the Somalia Affair, the misbehaviour of Canadian peacekeeping troops on duty in Somalia. There has been similar controversy since three murder-suicides involving Special Forces soldiers at Fort Bragg, N.C., in the summer of 2002. To date more than 19 cases of vestibular damage following the use of mefloquine have been diagnosed by military physicians. The same damage has been diagnosed among business travelers and tourists.

Neurological activity

In 2004, researchers found that mefloquine in adult mice blocks connexins called Cx36 and Cx50. Cx36 is found in the brain and Cx50 is located in the eye lens. Connexins in the brain are believed to play a role in movement, vision and memory.

Chirality and its implications

Mefloquine is a chiral molecule. It contains two asymmetric carbons, which means there are a total of four different enantiomers of the molecule. Mefloquine is currently manufactured and sold as a racemate of the (+/-) R*,S* enantiomers by Hoffman-LaRoche, a Swiss pharmaceutical company. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects. Some believe that it is irresponsible for a pharmaceutical company to sell mefloquine as a racemic mixture. It is not known whether mefloquine goes through stereoisomeric switching in vivo.

Advice to travelers

Mefloquine is one of the antimalarial drugs which the August 2005 issue of the CDC Travel Health Yellow Sheet advises travelers in areas with malaria risk — Africa, South America, the Indian subcontinent, Asia, and the South Pacific — to take.

There are virulent strains of malaria that are resistant to one or more anti-malarial drugs; for example, there are mefloquine-resistant strains in Thailand. Travelers are advised to compare current recommendations before selecting an antimalarial drug as the occurrence of drug-resistant strains changes.

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Army Studying Recent Suicide Spike
From Military Medicine, 4/1/04

According to Assistant Secretary of Defense for Health Affairs, William Winkenwerder Jr, the Pentagon will appoint a panel to design a study that will investigate whether or not an anti-malaria drug developed by the Army could be causing a recent spike in the suicide rates, one month after stating that the drug could not be a factor in the increase.

In late February, Wikenwerder stated that the Army could confirm 21 suicides in the Iraqi Theatre, which translates to a rate of 15.8 per 100,000 soldiers. This rate, slightly above the typical 9.1 to 14.8 range occuring between 1995 and 2002, is not significantly higher than the average according to Wikenwerder. The number does not include suicides among returning veterans, according to the Pentagon. At least six apparent suicides have occurred in this population. Another five deaths are also being investigated as potential suicides.

The drug, Lariam, developed by the Walter Reed Army Institute of Research, is used by soldiers in the Middle East to defend against malaria. The coming hot, moist summer months make getting this deadly disease more likely. According to the Food and Drug Administration, Lariam can cause not only thoughts of suicide, but also psychosis, paranoia, depression and aggression. No direct link has yet been established between the drug and actual suicides, though rare suicide reports amongst Lariam users do occur.

Only four of the 21 suicide victims came from units taking Lariam, and only one tested positive for it in the blood, according to Pentagon health officials. According to LTG James Peake, the Army Surgeon General, a soldier with a history of depression gets an alternate anti-malaria drug. Once mosquitoes in Iraq are tested for malaria, the Central Command surgeon will make the decision whether or not to use anti-malaria drugs in the region at all. They may, in fact, determine that the malaria risk does not justify use of a vaccine. This summer, the daily anti-malaria drug Chloroquine, instead of the more effective Lariam, may be given to soldiers in Iraq should a need for a drug be determined.

According to Col Thomas Burke, program director for mental health policy for the Assistant Secretary of Defense (Health Affairs), overall military suicide rates have remained constant for over a decade. Army rates may look higher, due to the relatively large Army footprint in the Iraq theatre, Burke said. all of the services are now taking a much more integrated approach to not only suicide prevention, but also to mental health care. In 2003, the Army sent over 500 soldiers from Iraq to mental health treatment facilities. Service members now get much needed support not only before and during deployments, but also receive evaluation and care upon their return home.

In addition to the leadership oriented military suicide prevention programs, co-workers, family members and military leaders can all help troubled service members before they make a decision to follow thru with suicide. Burke pointed out that military leaders should also be stressing that there's no stigma attached to getting help with mental health issues. In fact, a recent Marine Corps statistic shows that 75 percent of Marines who had committed suicide had not seen a mental health care provider within the year preceding their death, according to Burke.

References:

United Press International. DOD Now Eyes Lariam in Suicides. Military.Com, February 26th, 2004

Triggs, Marcia SFC. Army Study to Dispel Lariam Suicide Myths. Health.mil. February 26th, 2004.

Gilmore, Gerry J. 'No Epidemic' Number of Soldier Suicides in Iraq. Health.mil. February 26th, 2004.

Labbe, Theola. Suicides in Iraq, Questions at Home. The Washington Post. February 19th, 2004.

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