— Japan officials said the anti-flu drug Tamiflu should not be given to teenagers, after two boys aged 12 and 16 broke their legs jumping from the second floor of their houses.
The ban follows earlier cases of odd behaviour including some suicides in Japanese teens taking Tamiflu (see http://www.newscientist.com/channel/health/dn10527).
However, a large new study casts doubt over whether the drug is to blame for psychiatric problems.
The company that makes Tamiflu, Roche Holdings in Basel, Switzerland, told New Scientist that new data shows that people with flu are less at risk of psychiatric symptoms if they take the drug. David Reddy, in charge of Tamiflu at Roche, says the company is about to publish data, collected by two large insurance companies in the US, on 226,000 people with flu, of whom 101,500 took Tamiflu.
Between 2% and 5% of patients in both drug and non-drug groups had neuro-psychiatric symptoms including encephalitis (infection of the lining of the brain), delusion, delirium, anxiety and hallucination. But, says Reddy, people on Tamiflu had significantly fewer symptoms.
More than three-quarters of the Tamiflu taken globally so far has been taken in Japan. The number of people and time spent on the drug there now adds up to 380,000 patient-years, says Reddy. Japan's national suicide rate is 25 per 100,000 people. Therefore, by extension, 95 people should have committed suicide while they were on Tamiflu just ordinarily by now, and we haven't seen that, Reddy says. In fact, only two people are known to have committed suicide while on the drug.
Flu itself has neuro-psychiatric effects, when chemicals called cytokines produced as part of the innate immune response to the virus cause brain inflammation. But Tamiflu lowers the amount of virus, so it should reduce these effects, says Reddy.
John Treanor, an expert on flu drugs at the University of Rochester, has seen Roches data. There has not been a suggestion of neuro-psychiatric side effects [caused by Tamiflu] in the clinical trials [in people], and the database analysis they have done also doesnt show such an association, he told New Scientist. However, when you get reports like this it is important to investigate thoroughly.
The Japanese government says 54 people have died while taking the drug. Fifteen people aged between 10 and 19 have jumped from buildings, and another ran into traffic, while taking Tamiflu. Five of these have died since 2004, although it is unknown whether they intended to kill themselves. In addition, there have been seven reported cases of odd behaviour in adults taking the drug two of whom committed suicide.
Masato Tashiro, head of flu at Japans National Institute of Infectious Diseases, told New Scientist that the drugs withdrawal is a highly political and sensitive issue, rather than science. However, he says, we know too little about it. My personal concern is that Tamiflu might invade the brain through the blood-brain barrier.
The barrier forms a highly impenetrable layer of tissue that prevents many chemicals from crossing from the blood into the brain. In 2004, Roche said the drug should not be given to infants under one year of age, after experiments in mice showed it depressed brain activity and caused death in animals too young to have a fully-formed barrier.
Normally, Tamiflu cannot penetrate the barrier. But it becomes more permeable when the tissue is inflamed, as can happen in flu. Japanese doctors fear that Tamiflu might be getting into the brain, depressing activity and disinhibiting some behaviours.
South Korea, New Zealand, Taiwan and the European Unions medicines agency have renewed warnings to doctors to watch for odd behaviour in teenagers on the drug, but have not withdrawn it.
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