Do happy pills just make you sad?

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Drugs such as Prozac are known as selective serotonin reuptake inhibitors (or SSRIs).

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London - Depression levels in Britain continue to spiral. Last year alone, more than 43 million prescriptions for antidepressants were handed out - 25 percent more than three years before.

But are antidepressants the panacea we hope them to be?

Drugs such as Prozac were hailed in the early Nineties as wonder pills that would banish depressive blues for good. But in the past five years, growing scientific evidence has shown these drugs work for only a minority of people.

And now controversial research in a respected journal claims that these antidepressants can make many patients’ depression worse.

This alarming suggestion centres on the very chemical that is targeted by antidepressants - serotonin. Drugs such as Prozac are known as selective serotonin reuptake inhibitors (or SSRIs). Their aim is to boost the level of this “feel-good” chemical in the brain.

But the new research, published in the journal Frontiers In Evolutionary Psychology, points out that serotonin is like a chemical Swiss Army knife, performing a very wide range of jobs in the brain and body. And when we start deliberately altering serotonin levels, it may cause a wide range of unwanted effects.

These can include digestive problems, sexual difficulties and even strokes and premature deaths in older people, according to the study’s lead researcher Paul Andrews.

“We need to be much more cautious about the widespread use of these drugs,” says Andrews, an assistant professor of evolutionary psychology at McMaster University in Ontario, Canada.

Previous research has suggested that the drugs provide little benefit for most people with mild and moderate depression, and actively help only a few of the most severely depressed. Eminent psychologist Irving Kirsch has found that for many patients, SSRIs are no more effective than a placebo pill.

Two years ago, the Canadian Medical Association Journal reported a 68 percent increase in risk of miscarriage in women on antidepressants. And research in 2009 on Danish children found a small, but significant, increase in the risk of heart defects among babies whose mothers had used SSRIs in early pregnancy.

There is also growing evidence that long-term use in adults is linked to bleeding in the gut and increased risk of stroke.

The key to understanding these side-effects is serotonin, says Andrews. Serotonin is also the reason why patients can often end up feeling still more depressed after they have finished a course of SSRI drugs.

He argues that SSRI antidepressants interfere with the brain, leaving the patient vulnerable to a “rebound” depression of even greater intensity than before.

“After prolonged use [when a patient stops taking SSRIs], the brain compensates by lowering its levels of serotonin production,” he says, adding that it also changes the way receptors in the brain respond to serotonin, making the brain less sensitive to the chemical. These changes are believed to be temporary, but studies indicate that the effects may linger for up to two years.

Relapsing is not exclusive to SSRI drugs - it is, in fact, seen in all the classes of antidepressant medications - but Andrews believes that the risk is particularly strong with SSRI drugs.

Moreover, he warns that antidepressants can disrupt all the physical processes that are normally regulated by serotonin, adding that animal studies show only about five percent of the body’s serotonin resides in the brain. Most is housed in the gut.

It is used, among other things, to control digestion, form blood clots at wound sites, and regulate reproduction and growth.

So a drug that interferes with serotonin may cause developmental problems in infants, problems with sexual stimulation and sperm development in adults, digestive problems such as constipation, diarrhoea, indigestion and bloating, and abnormal bleeding and stroke in the elderly.

The drugs may also raise the risk of dementia. Most disturbingly of all, Andrews’ review features three recent studies which, he says, show that elderly antidepressant users are more likely to die prematurely than non-users, even after taking other important variables into account.

One study, published in the British Medical Journal last year, found patients given SSRIs were more than four percent more likely to die in the next year than those not on the drugs.

“Serotonin is an ancient chemical,” says Andrews.

“It is intimately regulating many different processes, and when you interfere with these things, you can expect that it is going to cause some harm.”

Stafford Lightman, professor of medicine at the University of Bristol, and a leading UK expert in brain chemicals and hormones, says Andrews’ review highlights some important problems, yet it should also be taken with a pinch of salt.

“This report is doing the opposite of what drug companies do,” he says. “While drug companies selectively present all the positives in their research, this selectively presents all the negatives that can be found. Both approaches are simplistic. And while SSRIs might possibly cause rebound depression, it is also sadly natural to expect that people with severe depression will see their illness come back, and often in a worse state.

“Nevertheless, the study is useful in that it is always worth pointing out that there is a downside to any medicine.”

Professor Lightman adds that there is still a great deal we don’t know about SSRIs - not least what they actually do in our brains. “It’s a bit embarrassing, but the bottom line is that we don’t really know how they work,” he says. “Basically, we started using these drugs before we understood what they do, because they showed some effectiveness.”

When it comes to understanding why the drugs work only for a limited proportion of patients, US scientists think they might now have the answer.

They think that in many clinically depressed patients, it’s not only the lack of feel-good serotonin causing their depression, but also a failure in the area of the brain that produces new cells throughout our lives.

This area, the hippocampus, is also responsible for regulating mood and memory. Research suggests that in patients whose hippocampus has lost the ability to produce new cells, SSRIs do not bring any benefit.

But why the hippocampus should do this - and how it should be treated - is not clear.

And even if those answers were found, they might still not produce a cure for many cases of depression, because the condition varies so widely in its causes and is so little understood.

What should be sure is that the days of doctors habitually prescribing SSRIs to all and sundry on the basis that they might work, and won’t do any harm anyway, really should be behind us. - Daily Mail

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