Japanese paediatricians are studying whether
Tamiflu, the drug widely thought to be our
best defence against avian flu, might be causing
mental instability and suicidal tendencies.
An initial study cleared Tamiflu of any link, but
that study, as well as a larger one that has just
started, are raising concerns about conflicts
of interest, as some of the researchers have
received large sums of money from the drug´s
Japanese distributor.
Countries around the world have been stockpiling
Tamiflu (oseltamivir) since 2004, in case
of a pandemic of avian flu. Japan is by far the
biggest user of the drug: in 2005, Japanese doctors
wrote 9 million prescriptions for Tamiflu,
compared with 3 million for all other countries
combined. But concerns about the drug’s safety,
which is made by Roche, have been growing
after some unusual deaths in Japanese teenagers
who had taken it. Most recently, a 14-yearold
girl and a 14-year-old boy died when they
jumped from apartment buildings on 16 and
27 February, respectively.

Tokyo-based Chugai Pharmaceuticals,
which distributes the drug in Japan, says that
it has reported 289 cases of psychoneurotic
effects, including three suspicious deaths, to
the Japanese health ministry since the drug was
launched there in 2001. Chugai now lists the
possibility of severe neurological side effects on
the drug´s labelling and has distributed a warning
note to hospitals. The Japanese health ministry
insists that there is no clear evidence of a
link, however, and points out that flu itself can
cause symptoms such as abnormal behaviour.
Roche agrees, adding that the number of suspicious
deaths is tiny compared to the number of
people who have been prescribed the drug.
Tamiflu was cleared initially when seven paediatricians
and a statistician looked at the side
effects of it and other influenza drugs, as well as
at the symptoms of flu itself. The study, which
ended in February 2006, followed up 2,846 children
aged mostly ten or younger who had been
diagnosed with flu. The frequency of abnormal
behaviour in children who took Tamiflu was
11.9%, compared with 10.6% in those who didn´t

take it, which the researchers concluded was not
a significant difference.
Shunpei Yokota, head of the study group and
a paediatrician at Yokohama City University’s
Graduate School of Medicine, admits that the
study had shortcomings, including a poor definition
for the term ‘abnormal behaviour’. So in
February, at the government’s request, Yokota’s
team launched a larger study, which will trace
10,000 people aged 0–18 years. The team aims
to release the results by this autumn.