Off-label prescribing of antipsychotic drug highlights lack of oversight

TORONTO – An increase in the number of prescriptions of a powerful antipsychotic drug for conditions not approved by Health Canada is raising concern about what medical experts call lack of professional and government oversight of doctors’ prescribing practices.

Also known as off-label prescribing, the practice is believed to be the reason why the number of prescriptions for Seroquel — a drug only approved in Canada for the treatment of bipolar disorder and schizophrenia — has nearly doubled in the last six years.

According to IMS Health Canada Inc., a company that tracks the health-care industry, the number of prescriptions for the drug has risen from 4.1 million in 2008 to 7.4 million in 2013.

In Ontario alone, claim counts for Seroquel have risen from 1.8 million in 2010-11 to 2.3 million in 2013-14, according to the Ministry for Health and Long-Term Care. The annual cost of the drug to the province reached more than $47 million in 2012-13, until generic products were introduced last April, bringing the total down to $38 million.

Some experts say prescriptions for Seroquel are vastly disproportionate to the number of Canadians suffering from schizophrenia and bipolar disorder — about one per cent of the population respectively, according to the Canadian Mental Health Association.

“Often what we see is people taking this drug primarily as a sleep aid, and that’s very bad medicine and I think that it’s something that should be discouraged,” says Dr. David Juurlink, head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto.

“I think that if doctors understood what exactly this drug was and how it worked and what its side effects were, they’d be very reluctant to prescribe it that way.”

Health Canada says some of Seroquel’s side effects can be fatal and include diabetes, hyperglycemia, constipation and intestinal obstruction, and complications from blood clots.

Off-label prescribing is not regulated by any one Canadian government body; Health Canada approves all drugs, regulations and policies regarding usage and prescribing, the provincial health ministries regulate the practice of medicine, but disciplining of doctors is handled exclusively by respective provincial regulatory bodies such as the College of Physicians and Surgeons — but only when a complaint is made.

When it comes to Seroquel and the way it should be prescribed in Canada, the answer varies depending on who you ask.

A spokeswoman for the Canadian Psychiatric Association says psychotropic medications are prescribed for “specific disorders, not for symptoms,” and that much of the off-label use is for treatment of specific symptoms such as sleep.

But Dr. Jitender Sareen, the head of the association’s research committee, says physicians prescribe medications off-label because some patients can’t tolerate the on-label drug, or it’s not available.

Off-label use does not mean inappropriate use, he said, as long as physicians inform their patients that they are using the medication off-label and explain to them its benefits and side effects.

Dr. Sareen says Seroquel prescriptions are rising because the drug has “beneficial effects” in more than psychotic illness.

“(Seroquel) is dangerous, it does have side effects — but if you look at the other medications that we prescribe in psychiatry for mental health problems, it is relatively safe … a small proportion of people do have difficulties with it but the reason that it’s used a lot is because people tolerate it reasonably well and it helps them with their depression, anxiety or psychosis.”

Juurlink of Sunnybrook says doctors should stick to Health Canada’s guidelines.

“This is a drug that can kill people, period. And it’s difficult sometimes to know who those people are going to be,” he says.

“When we give them to large numbers of people – hundreds of thousands or even millions of people — you’re going to harm a considerable number of patients, and I think in general drugs to help people sleep are a bad idea, and Seroquel is particularly a bad idea for that purpose.”

Health Canada says it monitors safety issues associated with the use of health products, including psychotropic drugs such as Seroquel, but adds the issue of off-label prescriptions falls under the “practice of medicine” and is provincially regulated.

Yet a Senate standing committee on social affairs, science and technology concluded in a report released in January that Health Canada could do more for drug safety as it is responsible for the post-approval monitoring of prescription drugs for both on- and off-label purposes.

The Senate committee also expressed its concern “regarding the manner by which physicians acquire information about approved prescription drugs.”

“Physicians are often unaware that they are prescribing off-label and that a lot of the knowledge that physicians have about medicines has been acquired through sales representatives from pharmaceutical companies,” the report states, adding that this practice is prohibited under the Food and Drugs Act.

In April 2010, Seroquel’s manufacturer — AstraZeneca Pharmaceuticals LP — was ordered by the U.S. government to pay $520 million to resolve allegations that the company was illegally marketing the drug for uses not approved as safe and effective by the Food and Drug Administration, such as for insomnia.

Health Canada has said that it is not aware of allegations of “similar advertising tactics” taking place in Canada.

The agency, however, told the Senate committee that it has received few complaints about the relationship between doctors and drug sales representatives, and the committee acknowledged Health Canada’s “inability to monitor the activities between physicians and drug sales representatives,” calling it essentially “unenforceable.”

AstraZeneca was not immediately available for comment.

South of the border, the Obama administration has introduced a new health-care law called Open Payments, which requires big pharma companies to disclose all payments made to doctors, from research grants to travel junkets, consulting and speaking fees. Newly released data shows the value of those payments totalled nearly $3.5 billion in the five-month period from August through December 2013.

No such law exists in Canada.

NDP health critic Libby Davies says that when it comes to off-label prescribing, the federal government is “sweeping it under the carpet.”

“It is a federal responsibility, it’s a very important responsibility and the more and more we find out about the lack of oversight and the lack of drug safety and the lack of transparency, I think Canadians are learning that we’ve got a pretty huge problem in this country.”

Davies says the New Democrats offered amendments to the newly passed Bill C-17 — or Vanessa’s Law — which included improvements to transparency and prescribing practices for off-label use, but they were turned down by the federal government.

Follow @adamsmiller on Twitter