The hidden cost of kicking the habit
A new drug
promises strong medicine in the battle against nicotine, but it may
produce unwelcome side effects
KRISTA FOSS
Every day, 113 Canadians die as a result of
smoking.
Alexandra, a hip, effervescent Toronto
professional, decided she wasn't going to let her pack-a-day habit
bury her in the anonymity of that statistic.
Last month, she tried Zyban. Friends had told
her that when it came to battling the demon of tobacco dependence,
Canada's first prescription-only, nicotine-free drug was
weapons-grade.
But Zyban made Alexandra feel really weird.
Normally ebullient, she became aggressive. A glass of wine made her
manic with chatter. She had a weekend of sobbing melancholy. On the
heels of that were body tremors which prompted her boss to send her
home. That was Week One of her prescription.
Alexandra may have had it easy. Since Zyban was
introduced to Canada last August, Ottawa's Health Protection Branch
has received 376 reports of adverse drug reactions. Of those, 234 were
ranked by the branch as serious, because patients had to go to
hospital as a result of taking the drug or have their current hospital
stays extended. Fifty of the reported drug reactions involved
convulsions -- some of the grand-mal variety. What's more, the drug
was suspected as a contributing factor in the cases of the three
Canadians who died while taking it. Granted, these people had complex
medical histories, including the fact they were inveterate smokers.
About 630,500 prescriptions for Zyban have been
issued since it arrived in Canada, according to IMS Health Canada, a
Quebec-based company that collects health statistics. So it can be
argued that 234 unconfirmed bad reactions aren't worth worrying about,
especially if cigarette smoking itself snuffs out the lives of more
than 40,000 Canadians a year.
But in fact, Zyban is raising some eyebrows,
and even ire, in the medical community. Nobody is going so far as to
suggest the cure may be worse than the poison. But if the cure doesn't
always cure, it seems fair to ask how much should be risked in an
attempt to get rid of the poison. "It is very unusual to get
300-plus adverse drug-reaction reports in the first year of marketing
a drug," said Rick Hudson, a medical consultant to British
Columbia's Pharmacare program and a self-described bête noire to
the pharmaceutical industry. "The question is whether the benefit
of the drug justifies the risk . . . and the answer is no."
Not everybody is taking no for an answer in
Canada. Zyban is a success story, contributing $34.3-million to Glaxo
Wellcome's sales in the first 10 months on the market according to IMS
Health, and peaking in March, when 82,175 prescriptions were issued.
"We've had a huge response rate; we're
thrilled," said Michael Levy, senior vice-president of research
and development for Glaxo Wellcome Inc. in Mississauga.
March was indeed a banner four weeks for the
drug. A study published in the New England Journal of Medicine that
month showed that twice as many patients who took Zyban were abstinent
at 12 months, compared to patients using placebos or nicotine patches.
When Zyban was used in combination with patches, even more patients
were smoke-free at 12 months.
Smoking is a notoriously tenacious addiction --
as many as 80 per cent of those who try nicotine-replacement therapies
such as patches or gum continue to smoke. Zyban appeared to be the
long-awaited answer to an addiction for which successful treatments
were in short supply.
Ken Bassett would like to see his patients quit
smoking as much as any doctor, but he has reservations about Zyban's
results. He is chairman of the drug-assessment working group for the
Therapeutics Initiative at the University of British Columbia.
Dr. Bassett said patients in recently published
clinical trials of Zyban were said to have abstained from cigarettes
if they had not smoked immediately before being examined by the
researchers. The final two examinations of patients in the trials were
six months apart -- so if patients did not smoke immediately before
each exam, it was assumed that they did not smoke at all in the
intervening months.
"Relatively few smokers ever stop smoking
completely. We have no idea if they simply were motivated to not smoke
right before being examined," Dr. Bassett said. "From an
earlier trial, we know that as many people went back to smoking if
they took Zyban as if they used nicotine-replacement therapy."
In fact, much of the marketing of Zyban has
rested on its nicotine-free status and its improvement over
nicotine-replacement therapy.
Certainly, nicotine is what addicts people. But
it is the 4,000 other chemicals in tobacco smoke that slowly corrodes
them from the inside out.
Dr. Levy describes Zyban's mechanism as
magical: "It is specifically targeted to addiction centres in the
brain. It works on noradrenaline and dopamine, reducing withdrawal
symptoms and decreasing craving," he said.
Zyban started off as the antidepressant
Wellbutrin, which its maker tried to bring to market in the late
1980s. The launch was held up when it caused a higher-than-predicted
number of seizures in bulimic patients. As the drug company put
Wellbutrin through new tests for safety, it also investigated
anecdotal reports that the antidepressant appeared to help patients
kick their smoking habits.
Wellbutrin was reformulated and approved for
sale in the United States in 1997 and in Canada in May. Months later,
Zyban hit the market in a Madonna-like reinvention -- same content,
new packaging and new audience.
Questions about the safety of buproprion
hydrochloride (the drug's medical name) remain, however. When
Alexandra became manic after a glass of wine, she called the Zyban hot
line operated by Glaxo Wellcome. The nurse told her that there were no
clinical studies on the drug's interaction with alcohol, so it was
best that she not have a tipple at all. (Health Canada's own
newsletter on adverse drug reactions notes that more knowledge is
needed about the drug's interaction with estrogen-replacement therapy
and other drugs, such as paroxetine. Dr. Levy says there have been no
contra-indications with other drugs.)
When Alexandra asked about the deep melancholy
she suffered, she was told by the Zyban hot-line nurse that she had to
allow herself to grieve the loss of smoking.
"She said that sense of depression was
described by a lot of people, that it was part of the grieving process
when you give up smoking. You feel like you're losing your best
friend. Some people even smoke more, they feel so anxious," she
said. "I realized . . . very little was known about the side
effects of this drug."
Another person who is wondering is Major Régis
Vaillancourt, a physician with the Canadian Armed Forces directorate
of medical policy and standards in Ottawa. Last fall, the military
decided to cover the cost of Zyban prescriptions if employees were
willing to join a group-counselling program to stop smoking.
Since then, Major Vaillancourt estimates that
about 1,000 military personnel have been prescribed the drug. Reports
of adverse reactions have tumbled in. Major Vaillancourt said there
have been several reports of what is known as serum sickness -- a skin
rash, fever, and joint swelling and pain -- putting people out of
commission for two to three days. He has received two reports of
patients experiencing seizures.
Adverse-drug-reaction reports themselves don't
make for good evidence -- they are anecdotal and unconfirmed and
because they are voluntary, it is assumed that they underestimate the
actual rate of side effects. However, they can flag unforeseen
problems with new drugs.
Major Vaillancourt thinks as much. In May, he
issued a warning to staff physicians to consider the risks and
benefits of prescribing the drug more carefully. He wants to study it,
too. This fall, he plans to survey military personnel who may have
used the drug, and then review the charts of those who had reactions
to it.
It seems that at the very least, all doctors
need to do a weightier cost-benefit analysis of prescribing Zyban. And
patients need to avoid thinking of it as a magic bullet. "If
you're not motivated to quit, and you're only smoking five cigarettes
a day, you might not want the risk of seizures," said Joel
Lexchin, head of the Ontario Medical Association's committee on drugs
and pharmacotherapy. "But if you're a 55-year-old smoker, you
have blood pressure and high cholesterol and all your relatives have
dropped dead of heart attacks at 50, you might want to take that risk."
Alexandra never made it to the second week of
Zyban -- her doctor advised her to stop. But she may try it again. A
colleague and veteran smoker successfully quit smoking with the help
of the drug. He said it saved his life.
Alexandra figures her smoking habit ultimately
represents a greater threat to her health than those little purple
pills. "I just wasn't ready," she said. "It could work
for a lot of people, you just have to be prepared for it . . . There
is no easy solution."
QUITTING TECHNIQUES: THE PROS AND CONS
ZYBAN (buproprion hydrochloride)
How it works: A prescription drug, Zyban is taken in a daily
150 mg dose for two days, then 300 mg thereafter, for total treatment
period of 7-12 weeks. It is speculated that the drug works on the
brain's neurotransmitters to reduce craving and the effects of
withdrawal from nicotine addiction.
Pros: Some
researchers have concluded that twice as many people abstain from
cigarettes after 12 months following one course of treatment with
Zyban, compared to similar treatment with placebos and the nicotine
patch. Because it is nicotine-free, treatment with Zyban means people
deal with their addiction to nicotine.
Cons: The
most common side effects from Zyban are insomnia, water retention and
skin rashes. But the rate of other side effects are controversial
especially when it comes to the number of people who experience
seizures and a serum sickness -- a feverish state in which the person
experiences joint pain. There are also concerns about the drug's
interaction with alcohol and other medications. Further, there is no
clinical evidence of the drug's effect among patients who have
recently had a heart attack or have heart disease.
NICOTINE REPLACEMENT THERAPY
Nicotine
patch and Nicotine gum
How it works: The gum and the
patch deliver nicotine at slower rates than cigarettes do, so they
have little addictive potential, but help smokers cope with the loss
of smoking.
-*Patches are meant to be used only after a person
stops smoking. A series of patches gradually delivers less and less
nicotine until the person is weaned off.
-*Gum can be used while
a person cuts back on smoking.
Pros: While nicotine
is the addictive substance in cigarettes, it is not toxic to the human
body. As a result, nicotine patches and gum let smokers have their
cake and eat it too -- without the noxious effect of cigarette smoke.
They also allow smokers to cut down on their cigarette intake by
allowing for smoking holidays -- and to cope with the difficulty of
not smoking while in smoke-free public buildings and transportation.
Cons: Almost 80 per cent of people who try nicotine
replacement therapies never kick the habit -- though some may smoke
less. |