Treating depression is an inexact balance of art and science.

Since you can't study live brains to see how any treatment really works, tackling the disease is somewhat like nailing jelly to the wall, says a leading expert.

Add that to the fact that more than half of depressive episodes eventually go away without treatment, and it's even harder to understand the disease, says Dr. Robert Cooke, of the mood disorders clinic at the Centre for Addiction and Mental Health in Toronto.

The resulting reality is that each day, millions of North Americans take pills to fight depression even though no one really knows exactly how they work.

"The brain is incredibly complicated (and) the mind is incredibly complicated," Cooke says. "There are still no simple answers or magic cures. We have treatments worked out on a trial-and-error basis and they are imperfect."

A mainstay of treatment has been antidepressant medication. But the earliest pills developed in the 1950s had significant side effects and could be highly toxic. By the late 1980s, with the advent of the new "designer" antidepressants, doctors thought they'd found a better answer.

The new drugs specifically target and change levels of the brain's chemical messengers " neurotransmitters. They were touted as "cleaner" drugs with fewer side effects and less toxic if taken in overdose.

They became so popular that sales of the drug Prozac " the first of the new class " hit $2.81 billion (U.S.) worldwide in 1998, and it became the fourth pharmaceutical product ever to eclipse $2.5 billion (U.S.) in global sales.

In Canada, from 1993 until 2002 the number of prescriptions for this class of drugs increased 768 per cent to 13.8 million, according to IMS Health Canada, a medical research firm.

Yet today, though millions of people are prescribed the new class of drugs, the new pills have not lived up to initial expectations.

"We need a major breakthrough in medications," Cooke says. "Most (used today) are copycats of older ones changed somewhat so they have fewer side effects. But the fact is, when it comes to effectiveness, the new drugs are no more effective than the ones we used in 1950s."

There is no doubt that changing neurotransmitter levels can affect mood, easing depression and mood swings, Cooke says.

Toronto's Glenn Hardcastle who has had bouts of depression all his adult life says he could never have fought the "molasses on the mind" without medication.

"It would be cruel to expect people to talk their way out when they are really down," he says. "For me, it was just not possible."

And Phil Upshall, spokesperson for the Mood Disorders Society of Canada, says the drugs help people out of their immediate crises so they can engage in talk therapy. Upshall, who has bipolar disorder, says medication was key to his getting his life back on track.

Though people on the medicine paint a glowing portrait of the drugs' benefits, the scientific evidence is not as clear-cut.

Studies show antidepressants help only 20 per cent of people who take them. That's based on controlled, double-blind trials which show that although 60 per cent of people respond to antidepressants, 40 per cent respond to a sugar pill, Cooke says.

But Dr. Barry Martin, another expert at the centre who runs its electro-convulsive therapy service, says that picture is incomplete because it only deals with patients who report improvement.

If you look at the number of people who completely recover on medication and compare it to people who take a sugar pill who report the same recovery, both are equally effective " about 40 per cent, he says.

However, Dr. Anthony Levitt, psychiatrist-in-chief at Sunnybrook and Women's Health Sciences Centre, says neither statistic is relevant. He says if you just look at depressed people left on waiting lists who are not involved in any studies, only 20 per cent improve on their own.

Besides the hazy picture of the drugs' effectiveness, other problems have emerged over the past 15 years as the newer medications have grown more popular.

Their side effects can be significant. The major ones are weight gain, sleep disturbance and sexual dysfunction, Cooke says.

Up to 30 per cent of patients using the neurotransmitter reuptake inhibitors report some sexual problem " either loss of desire, inability to have an orgasm, impotence or delayed orgasm. Hardcastle says he has experienced headaches, sexual dysfunction, agitation, sleeplessness and frequent urination as side effects in his search for a suitable medication.

Another concern has been the reports of physical withdrawal when people stop taking antidepressants " a problem Cooke says was "really underestimated."

In April, Health Canada warned doctors that "withdrawal reactions or discontinuation symptoms" occur with all the newer antidepressant drugs. It "may be misdiagnosed, leading to inappropriate treatment."

Cooke says people who stop antidepressants don't crave them for a high. But they can experience nausea and diarrhea. They may also have nightmares and can get a disturbing feeling like electrical sparks shooting through parts of their body, he says.

Bonnie North says she went through "agonizing withdrawal" when she tried to stop an antidepressant in 2001.

She had been on the treatment for three years to fend off depression after childbirth.

North suffered headaches, extreme nausea, vomiting and diarrhea. Most maddening, she says, was a constant sense of an electrical "zap" in her head that lasted for months. She has launched a lawsuit against the drug manufacturer.

The manufacturer will not comment on the court case but says its drug is safe and causes no severe withdrawal symptoms if discontinued properly under a doctor's supervision.

North also worries because there have been no studies of long-term side effects.

People like herself, who are put on the drugs for years, are "guinea pigs" she says.

Most of the pre-market studies of the drugs before they were approved for sale lasted six weeks. But many patients stay on the drugs much longer. That's because, unless the drugs are taken for a year, a patient is likely to have a relapse, Cooke says.

He acknowledges that information about long-term side effects is not available. But since the drugs are monitored after they hit the market, serious adverse reactions would be reported, he says.

Karen Liberman says she doesn't care about the lack of evidence from long-term studies.

The spokesperson for the Mood Disorders Association of Ontario says she went through "a decade of hell" trying 27 different medications as well as ECT before she found a drug that worked. But since she has been on it, she says, life is totally different.

"If it comes down to the risk of some long-term side effect that they don't know about, versus me having the quality of life I now have, I'd pick this good quality of life " even if (a side effect) made my life shorter," she says.

http://www.thestar.com/NASApp/cs/ContentServer?GXHC_gx_session_id_=b75356f47 36c5d8f&pagename=thestar/Layout/Article_Type1&c=Article&cid=1052251753634&ca ll_pageid=968867505381&col=969048872038

Prozac Is Part Of Our Culture

By Judy Gerstel

Toronto Star Staff Writer

6-6-3

Antidepressants are two of the top 10-selling drugs worldwide. Last year, Paxil ranked eighth and Zoloft was 10th. Effexor sneaked in at number 20.

The reason for this:

(a) Depression, and especially bipolar disorder, once known as manic-depressive disorder, is the disease du jour.

(b) Availability of new SSRI drugs for treating depression produced a pattern of the disorder the drug was capable of treating.

(c) Pharmaceutical companies have medicalized the normal problems of daily living in order to sell more drugs.

(d) We're all a bunch of self-indulgent, weak wimps who just need to pull up our socks, stop whining and get on with it.

(e) Life at the turn of the millennium the culture shock of new technology, social change, globalization has overstressed us, triggering an epidemic of depression.

The correct answer?

Clearly, depression is the disease du jour. And for sure the drug companies play a big role in creating that. But don't just blame Big Pharma for a whole lot of people having the same disorder at the same time. Chalk it up also to the herd instinct maybe the same one that makes us all want to wear white Gap shirts and drink Stellas and Cosmos. There's nothing new about the force of trends, even applied to disorders of the mind.

In the 1920s, writes Edward Shorter in A History Of Psychiatry, "psychoanalysis had become so fashionable among the middle classes in Berlin that people would chat about their `Minkos'," short for Minderwertigkeitskomplex, or inferiority complex.

Thirty years later, North Americans decided en masse that they needed to be calmed even though it was the '50s and in hindsight, they seem to already have been lobotomized. Miltown, a tranquillizer, became the first psychiatry drug to become "the object of popular frenzy," notes Shorter. Time magazine wrote about "happy pills." Television host Milton Berle referred to himself as "Miltown" Berle.

People in the 1970s were taken with the idea of anxiety and panic disorder. It seemed as if everybody was on Librium or Valium.

In the 1978 movie, An Unmarried Woman, Jill Clayburgh's character feels anxious and panicky while shopping at Bloomingdale's in Manhattan.

She looks in her purse for the pill she always carries with her but can't find it. "Does anybody have a Valium?" she calls out to onlookers in the store.

All the shoppers around her proffer Valium pills from their purses and pockets.

Audiences watching the movie laughed out loud with recognition.

In 1994, Time magazine declared, "Prozac has attained the familiarity of Kleenex and the social status of spring water."

Says Dr. Peter Kramer, author of Prozac Nation, by phone, "There are medicines that somehow meld well with the cultural needs at the moment, so that Miltown and Valium were very popular, each for different reasons."

One reason: "I attach it to changes in the role of women ... the anxiety of having to take the leadership role. These medicines (Prozac, et al.) make people more assertive. They not only recover from depression but are more energetic and less vulnerable to insult and humiliation qualities that working women need."

But the Zeitgeist alone isn't responsible for diseases du jour.

If a society's propensity for anxiety, panic disorder or depression is the tinder, a new drug can be the spark that fires the trend.

Drug companies were probably as surprised as anyone at the success of the SSRI antidepressants, suggests Kramer. "Once it started happening, they did some things to encourage it, but it happened largely through word of mouth, people's experiences, doctors' experiences."

As for the medicalization of daily life, critics charge the drug industry and medical establishment with medicalizing menopause and treating it with hormone replacement therapy, with medicalizing boyhood and treating it with Ritalin, and with medicalizing moods and rhythms of life and treating them with tranquillizers and antidepressants. But the latter isn't a strong argument.

What about (d) just pulling up our socks and getting on with it?

People who say that self-indulgence has led to the Prozac nation point to bygone eras when life was primitive, food and shelter were scarce, disease was rampant, predatory enemies and beasts abounded.

That, says Brown University psychiatrist Kramer, is not a valid argument. Most people didn't live long enough during, say, the 12th century, to experience the chronic relapses that characterize depression and the triggers for depression that come with the declining hormones and losses of getting older.

University of Toronto historian Shorter says that people have always been depressed but that it was given a different label.

"What our forefathers talked about was not depression but nervousness. It was very widespread in the 18th, 19th and early 20th centuries, very much a reality for lots of people."

The diagnosis of nervousness came to have a kind of "antique quality," says Shorter, and psychiatrists started talking about depression and anxiety instead.

He adds, "The idea that people just pulled up their socks in the past in a way that would be exemplary for us is a false idea.

"As a historian of psychiatry I know the extent to which depression and anxiety in the past were debilitating illnesses that ruined the lives of those whom they touched."

In fact, he says, "I don't seen any snivelling effect here at all. It's not that we've become weakened as a society and have lost our moral backbone because Prozac is as common in the medicine chest as Aspirin."

Agrees Manhattan psychiatrist Jeremy Mack, "It doesn't seem to me that we're pulling up our socks more or less. In the old days, people would drink, commit suicide, beat up wives and children."

Besides, say the experts, why should we suffer unnecessarily? Our ancestors died prematurely because they had bacterial infections. We don't die of those infections because we have antibiotics. Why should we deprive ourselves of effective therapy in the case of depression and anxiety?

So then (f) is the correct answer. It's not self-indulgence and softness that's sending us to fill prescriptions for Celexa and Effexor. It's the stressors of contemporary life that are making us depressed and a little crazy.

Well, no.

While stress is a trigger, says Shorter, stress doesn't cause depression. There's a genetic factor and "probably other factors that have to do with the brain."

Mack explains, "Life may be more complicated that it used to be, but stress does not necessarily translate into depression. It could show up as gastric conditions and other body ailments."

The correct answer to the quiz question: none of the above.

The real reason, when we needed anti-depressant pills for the picture on the front of this Health section, many people in the newsroom were able to reach into their pockets, drawers and purses to supply them (recalling the Valium scene from An Unmarried Woman) is because more people are willing to seek help instead of suffering and because effective relief is available.

"It's out of the woodwork," says Mack, "because there are things you can do about."

Concludes Prozac Nation author Kramer, "My sense of it is that more people are willing to admit to it."

Okay, we know that wasn't one of the choices in the quiz. It was a trick quiz. Does that make you sad, unhappy and depressed?

Go take a pill. If you don't have one, someone near you does.

jgerstel@thestar.ca

http://www.thestar.com/NASApp/cs/ContentServer?GXHC_gx_session_id_=83232bb07 36b6168&pagename=thestar/Layout/Article_Type1&c=Article&cid=1052251747545&ca ll_pageid=1054893767988