Bitter Pills

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Others struggle to see any role for the SSRIs. As they see it, if depressed people's brain chemistry isn't messed up before they start taking the drugs, it's stone-cold certain that it will be once they're on them. There's no evidence that any drug acts specifically to reverse depression, says Moncrieff. "It's more accurate to understand psychiatric drugs as inducing abnormal states, analogous to how we use recreational drugs to induce euphoria or social disinhibition." The most she can say for the SSRIs is that some of them are mildly sedating, "and this may help someone who is agitated or anxious." Lucire says they can also energize and brighten one's mood - but, she adds, so can cocaine. The SSRIs do more for men with premature ejaculation than for people with depression, says Dr. David Healy, of Cardiff University in Wales. Healy supports drug treatment for depression, but is a hero to many SSRI skeptics for his work in exposing the drugs' capacity to produce suicidal thoughts and, in what he estimates to be 1 in 500 of all SSRI users, drive people to kill themselves. The serotonin-imbalance theory has been a marketing tool for the drug companies, skeptics say. "It suggests a disorder a bit like a vitamin deficiency that will be put right by vitamins," Healy says, "when in fact the SSRIs produce marked abnormalities in the serotonin system."

Recent reviews of the data from SSRI trials indicate that placebos are on average 80% as effective as the drugs. But this is misleading, argues Parker. The typical subject in the trials, he says, did not have the more serious melancholic depression that doctors invariably treat with drugs but a milder form more likely to resolve spontaneously or from non-drug therapies. A view common among doctors is that if antidepressant trials looked exclusively at people with melancholic depression, the gap in efficacy between the drug and a placebo would widen.

Be careful suggesting to Auckland clinical psychologist Gwendoline Smith that SSRIs don't work much better than a sugar pill. When depression first hit her 10 years ago she was reluctant to use medication, figuring she could get well by exercising more, adjusting her diet and smiling in front of a mirror. But for that approach to work, she says, she'd have needed to practice it for six to 12 stress-free months on a secluded island. Instead, she went on the drugs and felt better in two weeks. Author of the recently reprinted handbook Depression Explained (ABC Books), Smith espouses the biological theory of depression, of which, in her view, serotonin deficiency is just a component. "The pathway into depression is via anxiety and the overproduction of cortisol," she says. Depression still descends on her intermittently. She can "feel the biology kicking in," she says; when that happens she knows she's left things too late to recover without drugs, which she uses on and off.

Smith says she suffers neither side effects nor withdrawal symptoms but accepts others do. Of those who do pay a price for less depression, many have no regrets. The pills may have switched off their libido and sapped their energy, they say; going off them may have triggered weeks of nausea and nightmares. But the drugs also hauled them out of a blackness from which escape had seemed impossible. "We know they work," says Smith. "Exactly how they're doing it . . . we haven't got that bit yet."

For many critics, though, the key problem with SSRIs is that they are too widely - and casually - prescribed. When the first antidepressant, imipramine (Tofranil), was developed just over 50 years ago, maker Ciba-Geigy balked at taking it to market for fear there weren't enough depressed people in the world to make it profitable. The wisdom of the time was that endogenous depression affected, at the most, about 1 in 1,000 people at some time in their lives. Things have changed. Groups such as beyondblue now promote the idea that about 1 in 5 people will become depressed during their lifetime.

The shift has caused many to ask whether prevalence has really increased 200-fold in half a century, or whether the definition of depression has been deliberately broadened and blurred by drug companies and others - part of a trend to medicalize moods that were once accepted as falling within the normal range of human emotions. Despite record sales of antidepressants in Australia, drug companies and mental-health lobby groups maintain there are still hundreds of thousands of Australians with undiagnosed depression.

The national charity SANE Australia is running a campaign - "Mental Illness is Real" - that challenges "misinformed community attitudes that discourage the 1 in 5 Australians affected by mental illness from seeking the treatment they need." Last year, Pfizer Australia urged G.P.s to be alert to depression in the country's three million arthritis sufferers. On the basis of a poll it had commissioned and interpreted, the company found 20% of these people had depression. Months earlier, working from another one of its surveys, Pfizer announced that "alarming numbers" of young Australians were at risk of depression because many around them were "dismissing telltale signs as normal adolescent behaviour."