According to researchers, selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressant drugs, but they may induce or worsen suicidal feelings in susceptible patients.

In the first study, researchers analysed 702 trials involving over 87,000 patients with depression and other clinical conditions to find out association between use of SSRIs and suicide attempts.

They found that patients taking these drugs were twice as likely to attempt suicide compared with patients taking placebo. They also didn't find any difference between patients taking SSRIs and those taking other drugs, known as tricyclic antidepressants.

The researchers say that the absolute risk of suicide is low, but the widespread use of SSRIs makes this a health concern.

The second study reviewed 477 trials submitted by drug companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA). These trials compared SSRIs with placebo in adults with depression and other clinical conditions.

Although weak evidence of an increased risk of self-harm was found in patients taking SSRIs, no evidence of an increased risk of suicidal thoughts was found in those taking placebo.

The final study was based on information from the General Practice Research Database. The research team analysed the risk of self harm and suicide in over 146,000 patients taking SSRIs and tricyclic antidepressants for the first time.

It was found that risks of self-harm and suicide were no different in patients prescribed SSRIs compared with those taking tricyclics. However, under 18s prescribed SSRIs seemed to be at increased risk of self harm.

The researchers point out that increased risks of suicide and self harm caused by SSRIs cannot be ruled out, but larger trials with longer monitoring periods are needed to assess the balance of risks and benefits fully.

"The debate is not yet done, but these papers crystallise arguments that have been drifting in the ether these past months. How many people who turned to 'happy pills' would not have done so if they had been fully aware of the potential harms?" said Kamran Abbasi, BMJ Acting Editor.

They recommend that patients should be warned of the potential hazard and monitored closely in the early weeks of treatment. They also discouraged the routine prescribing of antidepressant drugs in children and adolescents.

- At first, John Desjardin's health deteriorated slowly. His breathing became labored, and then he developed a chronic cough; during one fit, he cracked two ribs. Soon, he was having trouble speaking. Over-the-counter medications didn't help, so he went to a doctor.

And then another doctor, and another, and another.

"No one could pinpoint what it was," said Desjardin, 42. A lingering cold? A stubborn chest infection? After several months, a diagnosis of asthma and allergies was made. Drugs were prescribed, shots given.

But the North Providence, R.I., man's problems were not over. And his journey through the new world of pharmaceuticals was just beginning.

In 2001, Desjardin's whole body began to ache, and after more tests, he was found to have fibromyalgia, a chronic, incurable disease that causes pain, fatigue and insomnia. Rheumatoid arthritis was also diagnosed. Desjardin became depressed. He began to have migraines. He had to quit his job as a machine operator at a coffee warehouse.

His doctors, meanwhile, were experimenting with an array of drugs to lessen his suffering. "At one time, I had six doctor visits a week," Desjardin said. "They kept trying different medications to see which worked and which didn't. It was all trial-and-error."

Various drugs were prescribed for insomnia, but the one they settled on worked only intermittently, despite increasing the dose to the manufacturer's specified upper limit. Vioxx was prescribed for pain - until it was recalled, after revelations that it increased the risk of heart attacks and strokes. Desjardin received Zoloft for depression - but he was switched to another drug when he began getting dizzy and having suicidal thoughts.

Today, Desjardin takes 10 different prescription drugs a day.

"I think they finally have the combination right," he said. "I'm a little more comfortable."

Welcome to the Pharmaceutical Age, when prescription drugs promise to improve life for everyone. For millions of people, they do.

But for others, there is a dark side: as Desjardin discovered, prescription drugs can harm, even when taken as directed.

The federal Food and Drug Administration estimates that 106,000 hospital patients die every year from adverse drug reactions, defined as any unintended response to a medication; more than 2 million others who are hospitalized experience an adverse reaction but live. The FDA has no statistics for nursing homes or the community at large, but incidents are surely numerous.

Among the risks of prescription drugs:

- Side effects

Some are little more than annoying - yawning, for example - but others can be debilitating or deadly. According to "Physicians' Desk Reference," an authoritative guide to drugs, Zoloft can trigger more than 100 side effects, including those that Desjardins experienced. Others include weight gain, loss of libido, low blood pressure, high blood pressure, kidney failure, heart attack - even depression, the very condition Zoloft is supposed to relieve.

"Every drug has a side effect," said Dr. David Nganele, who was a senior product manager for the Zoloft brand at manufacturer Pfizer before leaving to become a consumer advocate and author. His latest book is "What you MUST Know About Prescription Drugs."

Nganele maintains that a patient must decide "what is the risk/reward ratio - is the benefit of taking this drug worth the side effect?" Someone experiencing stomach bleeding from taking aspirin might want to switch to Tylenol, he said. But a cancer patient might be willing to continue with a highly toxic drug "because the reward is they might stay alive."

- Interactions.

Some drugs interact with other drugs - and even common foods - to produce adverse reactions. Manufacturers and guides such as "Physicians' Desk Reference" list many of them, but with more and more drugs hitting the market every year, it is virtually impossible to compile comprehensive lists.

According to Nganele, thousands die or are harmed every year by drug interactions. He gave a simple example of what can happen: A patient who is taking Plendil to lower blood pressure might decide to eat a grapefruit, not knowing that the fruit inhibits the liver from processing the Plendil.

"You might end up with an overdose, which could reduce your blood pressure to a dangerously low level," Nganele said.

Desjardins would seem a likely candidate for an interaction - but he doesn't know if he's ever had one. "I can't tell," he said. "I'm on so many different medications."

- Long-term dangers

The FDA approves new drugs after clinical trials that involve, at most, a few thousand people and last a few months. But once on the market, a drug may be used by millions of people for years on end - a much broader opportunity for problems to surface. That was the case with Vioxx, launched in the United States in 1999. The drug rang up $2.5 billion in worldwide sales in 2003, the year before Merck pulled it from the market. (Government advisers recommended Friday that consumers should continue to have access to Vioxx and similar drugs; the FDA will decide whether to follow the recommendation.)

Especially in the wake of Vioxx, which may have caused as many as 55,000 deaths, critics assert that the FDA has no good system to track adverse reactions once a drug is on the open market. Critics also say that the agency relies too heavily on manufacturers' data, not its own.

- Prescribing errors.

According to Nganele, nurses or pharmacists sometimes wrongly read a doctor's handwriting on a prescription pad - or hear the wrong name when a doctor phones in a prescription. "There are lots of medicines that have similar sounding names. There are lots of instances of people who have died."

But the potential hazards of prescription drugs seem to have done little to dampen ever-increasing consumption.

Americans bought a record 3.5 billion prescriptions last year, according to IMS, a Connecticut-based consulting firm that processes data from drug manufacturers. That represented $235 billion at wholesale prices - an increase of more than 8 percent over 2003. Sales and prescriptions would have been higher if Vioxx had stayed on the market and if warnings about a similar drug, Pfizer's Celebrex, had not been issued. Sales of yet another popular drug, the antidepressant Paxil, also suffered, when New York state Attorney General Eliot Spitzer sued GlaxoSmithKline for allegedly failing to diclose data that implicated the drug in teen suicides.

But there's no slowing down: IMS predicts that sales of prescription drugs will continue to grow at an annual rate of 7 percent to 10 percent through 2008.