Research Finds Some Depression Drugs
Raise Cancer Risk

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Thursday, February 14, 2002 – Print Edition, Page A1

MONTREAL -- Certain kinds of antidepressants can double the risk of developing breast cancer, according to a landmark Canadian study.

Based on the finding, the lead researcher is recommending that physicians stop prescribing certain tricyclic antidepressants, and that women switch to drugs that do not risk damaging their DNA.

It is not known how many people the warning could affect. Millions of Canadians have taken or will take antidepressants over their lifetimes. About a quarter of people currently taking medication for depression are on tricyclic drugs, though not all are considered a risk.

"This is a common sense recommendation," said Colin Sharpe of the Centre for Clinical Epidemiology at Sir Mortimer B. Davis Jewish General Hospital in Montreal.

But at the same time, he cautions that the research needs to be replicated, and that other sorts of antidepressants need to be studied.

Tricyclic antidepressants that researchers say carry an increased risk of breast cancer include amoxapine (sold under the brand name Asendin), clomipramine (Anafranil), desipramine (Norpramin) and trimipramine (Surmontil and Rhotrimine). Paroxetine, another type of antidepressant sold as Paxil, has also been identified as carrying an increased breast cancer risk.

Tricylics and other antidepressants that do not carry increased risk include amitriptyline (Elavil), maprotiline (Ludiomil), nortriptyline (Aventyl), protriptyline (Triptil), sertraline (Zoloft) and fluoxetine (Prozac).

Many experts are warning that, while the findings are worrisome, the risk must be kept in perspective, and women should not stop taking medication for depression because they fear cancer.

"Women should not panic," said Marilyn Schneider, executive director of the Canadian Breast Cancer Research Initiative, which funded the research. "The risks and benefits of antidepressant medication have to be balanced, and the issue should be discussed with a physician before any action is taken."

The new research, published in the British Journal of Cancer, looked at the effect of 10 tricyclic antidepressants -- six of them genotoxic (shown to damage DNA in laboratory experiments) and four of them non-genotoxic.

Women who took the genotoxic drugs saw their risk of breast cancer more than double. Those who took the non-genotoxic drugs did not see their risk increase.

The breast cancer did not show up until 11 to 15 years after initial prescription of the medication.

"What happens is there is an immediate effect, but it's not detected until a decade later, or more," Dr. Sharpe said. He said the drugs seem to damage DNA, which promotes the growth of cancerous tumors.

More than one million Canadians are believed to currently be suffering from depression. During their lifetime, one in every four women and one in every eight men will require medical treatment for depression.

About 10 per cent of Canadian women and 5 per cent of men will take antidepressants at some point in their lives. About one in four of those women now take tricyclics, an older form of medication for depression.

In recent years, tricyclics have been largely overtaken by a new class of drugs with fewer side effects, called selective serotonin reuptake inhibitors (SSRIs).

Earlier research published by Michelle Cotterchio, a senior epidemiologist at Cancer Care Ontario, found that at least one popular SSRI may increase the risk of breast cancer.

She and her team found that women who took paroxetine (better known by its brand name Paxil) saw their risk of breast cancer increase seven-fold. In an interview yesterday, she said the findings should be treated cautiously. "You can't say from a single observational study, what people should or shouldn't do."

But, at the same time, Dr. Cotterchio said that, personally, she would consider switching from paroxetine to another drug because of the magnitude of risk that showed up in the research.

The study, published in the American Journal of Epidemiology, also showed a doubling of the breast cancer risk among women who took tricyclic antidepressants for two years or more.

Dr. Cotterchio said that, more than anything, more research is needed, particularly on the link between SSRIs and cancer. "From a public health point of view, SSRIs are a much greater concern than tricyclics because so many people take these drugs," she said.

Allan Steingart, an assistant professor of psychiatry at the University of Toronto who also has a busy clinical practice, said that SSRIs are endocrine disruptors, and they can alter estrogen levels. Side effects include changes in breast cancer density, lactation in women who are not pregnant and sexual dysfunction.

But Dr. Steingart cautioned that the risk of cancer has to be balanced against the benefits of dealing with depression, a debilitating disease. "The benefits of antidepressants are tangible when they work. They can change lives, and save lives," he said.

"You have to weigh the risks of cancer against the risks of depression. We can't compare risk to no risk, that's a false calculus," Dr. Steingart said.

He said that because of the growing popularity of antidepressants, however, there should be a lot more research. Antidepressants are now used to treat chronic pain, premenstrual syndrome, bulimia, attention deficit hyperactivity disorder, panic disorder, obsessive-compulsive behaviour and smoking cessation.

"Informed choice is really the issue. Patients should know the risks, as well as the benefits of all the drugs they take," Dr. Steingart said. But, in his clinical experience, patients who are told about the possible cancer risks a decade or more down the road "tend to take the drug anyway" because they get immediate relief from their symptoms of depression.

None of the scientists suggested that the drugs be removed from the market.

Researchers at the Jewish General conducted their research using data from the Saskatchewan Prescription Drug Plan that was collected between 1981 and 1995. They looked at the prescription records of women 35 years and older with no history of cancer since 1970.


A list of antidepressant drugs that are associated with an increased risk of breast cancer was derived from two separate studies. Drugs are by chemical name, followed by examples of brand names.

Increased risk
Tricyclic antidepressants
Amoxapine - Asendin
Clomipramine - Anafranil
Desipramine - Norpramin
Trimipramine - Surmontil, Rhotrimine

Selective serotonin reuptake inhibitors (SSRIs)
Paroxetine - Paxil

No increased risk
Tricyclic antidepressants
Amitriptyline - Elavil
Maprotiline - Ludiomil
Nortriptyline - Aventyl
Protriptyline - Triptil

Selective serotonin reuptake inhibitors (SSRIs)
Sertraline - Zoloft
Fluoxetine - Prozac

-* Note: Studies of the drugs doxepin and imipramine produced conflicting results.

Source: British Journal of Cancer, Jewish General Hospital, Montreal, American Journal of Epidemiology, Cancer Care Ontario

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