New Antidepressants Widely Praised, but Some Fear Overuse
It’s just a little green and white pill, but it’s got the name recognition--and some would say the devoted following--of a rock star.
Twice, the antidepressant Prozac has been featured on the cover of Newsweek. It has been the subject of several books, including one bestseller.
But not everyone is an avid fan. Critics say that it is grossly overprescribed and that its long-term effects are unknown. Others say it is no replacement for a stint on the psychotherapist’s couch.
Meanwhile, more than 20 million people in 100 countries have partaken of this flagship drug, the first in a new generation of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Last year, sales climbed 24% to $2 billion.
And the competitors are coming up fast: The makers of another serotonin-enhancer, Zoloft, sold $1.4 billion worth of the drug last year, a 45% rise over 1994. Third-ranked Paxil’s manufacturer sold $782 million worth, up 51%.
What accounts for these medication-sensations?
Oddly enough, it isn’t so much that they are more effective than their predecessors. About two-thirds of patients respond to any given antidepressant. Eli Lilly, Prozac’s manufacturer, puts its effectiveness at 70%.
These drugs are simply more tolerable. They can be prescribed more widely, for a longer period, with less risk of serious side effects. Patients are more likely to stick with the program. The drugs are nonaddictive, they don’t produce an amphetamine-like “high” and they are nearly impossible to use, by themselves, as a means of committing suicide.
“It is not a happy pill,” Dr. Steven Paul, vice president of Lilly Research Laboratories, said of Prozac.
SSRIs, however, are more than just antidepressants. Prozac and Paxil are approved by the Food and Drug Administration to treat obsessive-compulsive disorder, and Zoloft is awaiting the FDA nod. Paxil is also approved for panic disorders.
The drugs are also prescribed legally by physicians for such “off-label” uses as treating bulimia, weight problems, premenstrual syndrome, alcohol and nicotine addictions--even gambling and compulsive shopping.
Although the precise reasons for their widespread powers are not known, UC San Diego researcher Stephen M. Stahl points to activity in four serotonin pathways in the brain--each of which mediates different effects. The drugs prolong the effects by enhancing the neurotransmitter’s concentration in the synaptic cleft (the space between brain cells, or neurons).
There is a downside. The SSRIs have their own set of side effects: occasional nausea and vomiting, anxiety, insomnia, headaches and sexual dysfunction.
“The reality is they are pretty damn good,” said Stahl, an adjunct professor of psychiatry at UC San Diego. “But they aren’t as good as some people say.”
Critics’ concerns range from the physical to the philosophical.
Shortly after Prozac rose to prominence in the early 1990s, allegations surfaced, in lawsuits and anecdotes, that it prompted violence and suicide.
But the drug companies, along with other clinicians and researchers, have fairly successfully dismissed these as unproven. “There is no credible, objective evidence,” Paul said.
Dr. Peter Breggin, a Maryland psychiatrist who has made a side career out of lambasting what he considers “toxic” psychiatric drug treatments, laments that Prozac may have become “our national prescription drug.”
“In less than a generation, we have rejected the motto, ‘Just say no to drugs,’ and adopted the motto, ‘Take this drug to improve your life,’ ” Breggin writes in his 1994 book, “Talking Back to Prozac.” “It is time for opposing voices. It is time to talk back to Prozac.”
Breggin also was talking back to Peter Kramer, a psychiatrist who in 1993 published a provocative, sometimes whimsical bestseller, “Listening to Prozac.” The book is an exploration of the author’s experience treating patients who may not meet the definition of clinical depression, yet find themselves positively transformed by the drug.
After the Kramer book, even Eli Lilly felt the need to stress Prozac’s primary mission as an antidepressant. In advertisements two years ago, the company warned that it ought to be prescribed only “where a clear medical need exists.”
In reality, however, Prozac and other SSRIs are prescribed for a variety of purposes, often by general practitioners not necessarily well-schooled in the intricacies of mental illness.
Some mental health experts believe the drugs are overprescribed without a good understanding of whether side effects will emerge, say, 20 years from now.
“Unfortunately, we’ve got an experiment going on right now with . . . millions of people,” said David Antonuccio, a psychology professor at the University of Nevada School of Medicine.
SSRI proponents point out that diabetics take insulin for life and patients with high blood pressure take anti-hypertensives without drawing the same outcry. And Prozac’s maker says the drug, approved by the FDA eight years ago, shows no signs of trouble. “It’s not 20 years, but things look good,” Paul said.
It is always useful to consider non-drug treatments, says National Institute of Mental Health Director Steven Hyman. But “if somebody is suffering a depression-like distress, and they take a medication and they get a lot better, who could rightly tell them to stop it?”
Some clinicians warn that a drugs-only approach to treatment assigns minimal importance to such intangibles as human will and courage.
“We know that Winston Churchill had manic-depressive illness--but he had a country to run; he had a war to fight. There are people who would be totally incapacitated by that,” said UCLA psychiatrist Jeffrey Schwartz. “Am I saying they are weak? No. Am I saying that Churchill was heroic? Yes, I am.
“The [strictly] biological people are making an egregious error by removing the heroic struggle of some people against their illness. It’s not all about chemicals . . . not all left to doctors.”
Psychotherapy, as traditionally practiced, is under enormous pressure. Many patients don’t bother with therapy anymore, relying on their general practitioner to dash off a prescription instead.
For patients, drug treatment often is less expensive. A visit to a medical doctor is often reimbursed more fully than one to a counselor.
The very nature of psychotherapy is changing, largely because of the pressures of managed care. But Prozac and drugs like it often are seen by employers and insurers as better investments than long-term therapy.
Psychotherapists are under pressure to prove that their techniques work as well--and as fast. Hence the push toward “time-limited” sessions and by-the-book approaches that are easier to monitor.
The issue isn’t simply effectiveness, but cost-effectiveness. For psychotherapists, this is a sore point because they see what they offer as more than time-limited relief.
Economics aside, researchers sometimes disagree on what works best--psychotherapy, drugs or a combination. Concerning depression, studies comparing older antidepressants to therapy have reached conflicting conclusions.
The point, say mental health advocates, is to expand treatment options, not to lop them off in the name of short-run savings. Therapy and drugs should not be either-or propositions, they say.
“For our population, a pill is often necessary,” said Laura Lee Hall, a neuroscientist and deputy director at the National Alliance for the Mentally Ill. “But a pill alone is usually not enough.”
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How Prozac Works
Prozac is the best known among a category of drugs called selective serotonin reuptake inhibitors (SSRIs). Here is how they function in a synapse, the connection between two neurons, or brain cells.
1) A portion of the SSRI molecule inserts itself in the synapse’s serotonin reuptake pump, which normally shuttles the neurotransmitter serotonin back into the neuron to be reused.
2) If the pump is blocked with Prozac or another SSRI, the serotonin lingers longer in the synapse, which researchers believe has an antidepressant effect.
Source: “Essential Psychopharmacology,” by Stephen M. Stahl, UC San Diego; Scientific American, National Geographic
