Safe when taken as directed.

But Xanax, Valium, Lunesta, Restoril and Ambien, the various and assorted sleeping and anti-anxiety medications found near the corpse of Heath Ledger in his Manhattan apartment last week might have conspired to kill the troubled 28-year-old actor.

In combination, in the wrong person, they may not have been safe at all.

The Australian heartthrob, famous for his portrayal of a gay cowboy in the movie Brokeback Mountain, was both an insomniac and dogged with anxiety and depression.

Ledger knew the frustration of chronic sleep loss, and was forthcoming in an interview last November while promoting the Bob Dylan biopic I’m Not There.

“Last week I probably slept an average of two hours a night,” Ledger told The New York Times. “I couldn’t stop thinking. My body was exhausted and my mind was still going.” He said two Ambien pills worked for only an hour.

“Insomnia is an enormous problem in North America,” says Dr. Gilles Lavigne, president of the Canadian Sleep Society, who estimates 30 per cent of Canadians suffer from intermittent bouts of insomnia, trouble falling or staying asleep, or waking up too early. Worse, 10 per cent of Canadians suffer from chronic insomnia, he says. The line is drawn when lack of sleep starts to persistently interfere with daytime functioning and mood.

Dr. Charles Morin, of Laval University in Quebec City, is a world leader in insomnia research. Author of Insomnia: Psychological Assessment and Management, Morin estimates, “four in 10 chronic insomnia sufferers also experience concurrent psychological problems such as anxiety, depression and substance abuse.”

Much of Morin’s research centres on cognitive/behavioural treatments, such as distraction therapies. Medications, he says, should only be considered as short-term solutions.

Some sleep disorder researchers have drawn connections between insomnia and creativity – a well-documented Ledger trait.

Wende Wood is a psychiatric pharmacist at the Centre for Addiction and Mental Health in Toronto. She says insomnia is a symptom of an underlying disorder that can include pain, depression and stress, “just like nausea is a symptom of food poisoning.”

“It takes a while to find the underlying cause and sometimes in the rush, prescriptions are written as a Band-Aid,” she says. For example, a patient who complains of anxiety or depression will be prescribed Effexor or Prozac. But according to Wood, because those drugs can take four to six weeks to kick in, a sleeping pill like Lunesta or Restoril is prescribed to help in the interim. “All along, sleeping pills have been used for short-term symptomatic use,” she says, “perhaps one to two weeks, long enough to establish a sleeping pattern.”

Although it’s ultimately a doctor’s discretion about the quantity and length of prescriptions, which are sometimes checked by wary pharmacists, sleep-inducing drugs dispensed to most patients should only be for up to a month’s supply, particularly at the onset of treatment, Wood explains. Drug therapies to treat patients with anxiety and depression usually involve longer-term treatments.

“To become fully physically dependent on sleeping medications takes a couple of months,” says Wood. “But you can become psychologically dependent more quickly. It depends on the person.”

She acknowledges there is potential for confusion and divides sleeping aids into three categories:

Benzodiazepines such as Valium and Diazepam, which are prescribed for both sleep and anxiety.

Drugs that are exclusively prescribed for sleep, such as Imovane, or Lunesta and Ambien (neither commercially available in Canada).

Other medications like trazodone and Benadryl, which can cause drowsiness as a side effect.

Many of these medications depress the central nervous system, she says. And when multiple medications are ingested, they can have an “additive” effect, especially in slowing respiration, which can be deadly.

“One plus one doesn’t always equal two,” says Wood. “If you’re lucky, one plus one equals three. Sometimes, in terms of overdose potential one plus one equals 10,” says Wood. For example, “all benzodiazepines work on the same receptors in the brain,” she says.

Worry travelled the world last week as a result of Ledger’s death and the drugs found at his home, travelled the world last week. “All of the drugs on that list are considered to be centrally acting respiratory depressants,” Dr. Terrence Blaschke told Newsweek Web reporter Karen Springen.

At the Toronto Sleep Institute, clinicians treat disorders such as jet lag, shift-work sleep disorder, narcolepsy and circadian rhythm disorder (people who can’t sleep at appropriate times). But insomnia tops their list. Short-term, problem-focused cognitive behavioural therapy is offered to help patients regain control over their sleep.

While the Ledger tragedy had insomniacs checking their meds, fear of dependence keeps most people away from prescription sleeping pills, says Morin.

Even when sleep is problematic, Morin says, “the majority of people do nothing. The first step they’ll (eventually) take is to hit the drugstore for one of the over-the-counter medications such as Nytol or Sominex or Tylenol PM.” But Morin does not recommend these products because they contain antihistamines and can cause daytime drowsiness.

More troubling is the number of people who turn to alcohol as a sleeping aid. “Alcohol slows down the whole brain,” Wood says. “It is a blunt object.”

Adds Morin: “We completely underestimate the number of people who use alcohol.” Remarkably though, he adds, “an extremely small portion of Canadians will go to their physician for a prescription. In Canada we are pretty conservative users of such medications.”

Only about 9 per cent of those suffering from sleep disorders will resort to some type of sleep-inducing drug, he estimates, adding that “today’s sleeping medications are much safer than they were years ago.” Patients need to take these medications in three or four times the recommended dosage to cause serious side effects, and 10 to 15 times to be lethal.

“People are too quick to blame the drug exclusively. These are not the powerful barbiturates that killed Marilyn Monroe.”

Ambien (a.k.a. zolpidem tartrate in its generic form) has been grabbing headlines – the side effects connected with zolpidem would keep anyone awake. In a small percentage of patients, side effects include allergic reactions, abnormal thinking and behaviour, amnesia, anxiety, other neuro-psychiatric symptoms and depression of the central nervous system.

Ambien’s maker, Sanofi-Aventis, insists the drug’s record after 13 years of use proves it is safe when taken as directed. According to IMS Health, Ambien sales in 2005 reached $2.2 billion.

Still, the company and the U.S. Food and Drug Administration have been pressured by doctors, Ambien users and legal professionals to include even stronger warnings about he drug’s side effects, especially its interaction with other drugs and alcohol.

David Graham
Living Reporter