Antidepressants not as good, or evil, as believed

Misunderstood meds
Kim Carney /
/ Source: NBC News

Antidepressant drugs have sparked some of the most contentious and long-running battles in the history of medicine. The Food and Drug Administration's decision last week to change the labels on the drugs is not likely to quiet the shouting.

Since October 2004 the FDA has required black-box warnings — the strongest alert of danger — on the medicines, noting a potential for young people taking antidepressants to have suicidal thoughts and behavior. With its latest move, the agency extended the warning to include 18- to 24-year-olds, but not to those age 25 and over. At the same time, the agency altered the label to note that “depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide.” 

So do antidepressants prevent suicide or cause it?

The FDA says they do both. That is only one of the many conflicts. One can also argue these drugs are used far too often in certain situations and far too little in others.

'Better than well'
The saga began in December 1987 when Prozac hit the market. It was the first in the class of drugs called SSRIs (Selective Serotonin Reuptake Inhibitors)that now includes Zoloft, Paxil, Effexor, Luvox and Lexapro. It's widely believed that SSRIs are designed from a firm understanding of the brain chemistry of depression, but, like most drugs, they were developed more through serendipity than science. Their mode of action resembles cocaine, ecstasy and methamphetamine, although they do not cause rapid euphoria or the difficult crash.

The major advantage of the SSRIs over earlier antidepressants is that it is almost impossible to overdose on them. They lack other severe side effects of earlier drugs such as toxic interactions with certain types of foods. There is no doubt SSRIs can effectively relieve depression for many people. 

With the National Institute of Mental Health estimating that 14.8 million adult Americans suffer major depressive disorder, it is hardly surprising that Prozac and its chemical cousins became celebrities in the world of pharmaceuticals.

In 1989 Newsweek featured a Prozac capsule on its cover. In his 1993 best-seller "Listening to Prozac," psychiatrist Peter Kramer described patients who underwent transformations of their personalities and felt “better than well” on the drug. Kramer speculated about our culture “facing the prospect of cosmetic psychopharmacology,” where people would be using medications for enhancement, not simply to treat depression or other mental illnesses.

In response to this groundswell of enthusiasm — as well as drug-company marketing — the uses for the SSRIs rapidly expanded far beyond depression.

“It’s almost a misnomer at this point to call them antidepressants,” says Dr. Joseph Glenmullen, a clinical instructor in psychiatry at Harvard Medical School. “They are used for anxiety, obsessive-compulsive disorders, gambling, even nail biting. They’re sort of all-purpose ‘feel better’ medications.”

Suicide danger real, but tiny
While SSRIs are not as dangerous as their predecessors, they’re still replete with side effects.  Reports of people, especially youngsters, killing themselves while taking Prozac and other SSRIs were reported almost as soon as the medications appeared. At first the drug companies and many psychiatrists wrote the suicides off as an inevitability in treating large numbers of depressed people, saying many of them would have killed themselves anyway.

But as media reports and lawsuits about the suicides proliferated, the FDA started to take the matter seriously and ordered a look at all the studies done on the drugs. It turned out to be a difficult task. Drug companies had carried out few studies in children. The studies in both adults and children usually lasted a short time — often only 12 weeks.

Ultimately, based on the available data, the FDA ordered black-box warnings on the medications for children in 2004 and for young adults last week. Most experts say the suicide danger is real and doctors need to monitor young patients closely, especially in the first few months of treatment. One hypothesis holds that as the drugs start to work, young minds become disinhibited just enough to start talking more about suicide and possibly attempting it.

As frightening as this side effect is, it is important to note it is tiny. Suicidal thoughts (and almost no actions) were recorded in 1.4 percent of children taking the drugs and 0.5 percent of the young adults.

The biggest problem with the SSRIs is all the other side effects that are far more frequent: sleeplessness, anxiety, weight gain, nausea and very commonly, a loss of libido and difficulty achieving orgasm. 

Dr. Peter Kramer told me recently that with the side effects as we now understand them, it would be wrong to use current antidepressants for the “cosmetic psychopharmacology” he speculated about in “Listening to Prozac.”

“I just don’t think doctors have the social permission now to treat things that fall shy of even minor mental illness,” he said.

To make matters worse, studies show that the drugs seldom work like magic bullets to alleviate symptoms in chronically depressed patients. Most need to try different drugs in varying doses until they get adequate relief.

“You can’t give just give these medicines and say ‘come back in six months and tell me how you did.’ These are serious drugs,” Kramer said.

Unfortunately, in the real world of medical practice that is usually what happens. General practitioners with no special expertise write many of the prescriptions. Studies show that most patients simply stop taking the medications because they don’t experience benefits and can’t stand the side effects.

As a result, depression — a widespread illness that not only increases the risk for suicide, but also for heart disease, cancer and many physical ailments and social problems — remains vastly undertreated. Statistics show that when the FDA began debating the suicide risk for children in 2004, prescriptions for the drugs to adolescents fell, while the suicide rate, which had been declining for years, went up.

SSRIs drugs are neither the evil that many believe, nor the magical solution that many hoped. However many prescriptions may be written for frivolous uses, the overriding message from this debate should be that we need to do a far better job of treating depression, with and without the medicines.