Most newer schizophrenia drugs no better – study

By Gene Emery

BOSTON (Reuters) – The first direct comparison of five
schizophrenia drugs found that most newer treatments are no
better than an older generic drug, despite their higher cost, a
U.S. study released on Monday showed.

The lone exception, Eli Lilly and Co.’s Zyprexa, may be
better than the other medicines but users experienced dramatic
weight gain and developed a higher risk of diabetes, the new
study concluded. The drug is also the most expensive.

The $44 million study, financed by the National Institute
of Mental Health and to be published in Thursday’s New England
Journal of Medicine, indicates “substantial limitations in the
effectiveness of the drugs,” said Columbia University’s Jeffrey
Lieberman, who led the team.

But it should also help doctors choose the best therapy for
the 3.2 million Americans suffering from schizophrenia, the
tough-to-treat mental illness marked by delusions,
hallucinations and scrambled thinking.

Because the effectiveness of a drug can vary from person to
person, side effects can force patients to stop taking them or
can cause doctors to switch between medicines and alter dosages
to find the best, most tolerable treatment.

The new study is the “largest, longest and most
comprehensive” assessment of anti-psychotic medicines ever
conducted, said the institute’s director, Thomas Insel.

It used the amount of time patients stayed on a drug to
help gauge its effectiveness. In all, 74 percent of the 1,432
volunteers at 57 study sites stopped taking the medication they
were originally assigned.

Only the schizophrenics taking Zyprexa, also known as
olanzapine, stuck with it significantly longer than the other
four. But even 64 percent stopped taking it after 18 months.

The discontinuation rate was higher among the other four
drugs: Seroquel (quetiapine) from AstraZeneca Plc; Risperdal
(risperidone) from Janssen Pharmaceutica, a wholly owned unit
of Johnson & Johnson; Geodon (ziprasidone) from Pfizer Inc.,
and perphenazine, which has been around since the 1950s and is
available in generic form.

The researchers also found that people on Zyprexa were less
likely to be hospitalized for a psychotic relapse.

While 15 to 20 percent of patients taking the other drugs
ended up in hospital because their condition worsened, the rate
was 11 percent for recipients of the Lilly drug.

It said one surprise was perphenazine’s side effects such
as tremor, rigidity, stiff movements and muscle restlessness
were not as common as expected. Patients tolerated it just as
well as some newer drugs, and it was no less effective.

Lieberman said the fact that the older drug was at least as
good as three of the newer medicines and almost as good as
Zyprexa was “the biggest surprise.”

And perphenazine was far cheaper.

At the average doses used in the study, a month’s supply of
perphenazine capsules costs about $50 — compared with roughly
$390 for Geodon, $425 for Risperdal, $475 for Seroquel, and
$660 for Zyprexa. Physicians determined the actual dose each
patient received.

Over $10 billion is spent in the United States each year on
such drugs, Insel said.

Weight gain among patients on Zyprexa was significantly
higher. Patients on the drug typically added two pounds (0.97
kg) a month. With two of the other drugs, patients gained up to
half a pound (0.23 kg) and with the other two, they lost a
small amount of weight every month.

And while all five drugs raised blood sugar levels, the
gains were more than twice as high for Zyprexa compared to
levels in volunteers treated by the other medicines.