Monday, April 21, 2003
Copyright © Las Vegas Review-Journal
ANTIDEPRESSANTS: Panacea or Placebo?
Newest medicines help many patients, but some studies question the drugs' efficacy
By JOAN WHITELY
REVIEW-JOURNAL
Are the new antidepressant drugs overhyped and overused?
Some patients don't care what critics think. They swear the drugs saved their lives.
"I was having suicidal thoughts," is how John Reynolds, a 20-year-old University of Nevada, Las Vegas student describes his mental health three years ago. Since then he has been on Effexor, with a total turnaround in his diagnosed conditions: generalized depression, bipolar disorder and attention deficit hyperactivity disorder.
"It helps you see clearer and understand things better, so you don't go off the deep end." Las Vegan Georgene Bratta, 54, is talking about Zoloft.
She started on an antidepressant about 16 months ago for depression that set in after she was diagnosed with Hepatitis C and had to go undergo difficult medical treatment. Bratta switched to Zoloft about seven months ago because she didn't like the tremors her first medicine was causing.
"I had very ferocious mood swings," begins Southern Nevada resident Shelley, 37, who declined to publish her last name. After using illegal drugs off and on since age 12, Shelley went to a doctor at 36 because relatives told her she got irritable as her menstrual cycle approached.
Shelley had more than monthly lows. Eventually she was diagnosed with bipolar disorder, attention deficit hyperactivity disorder and obsessive-compulsive disorder. That's when she began her present regimen of several drugs, including Zoloft.
When she was untreated, "I wasn't conducive to life, to society," Shelley jokes. Before going on antidepressants, she had run-ins with the law and difficulty holding jobs. On Zoloft, she is noticeably calmer and more reasonable, her relatives say.
Shelley rejects the criticism of the latest generation of antidepressants as a trendy quick fix. She opposes the stigma against people who take them. "You should be thankful I'm on them."
Zoloft belongs to a new class of drugs called SSRIs. The name stands for selective serotonin reuptake inhibitor. The drugs improve mood by balancing brain chemicals called neurotransmitters. In particular, they slow metabolism of the neurotransmitter serotonin to increase serotonin levels in the brain.
Effexor technically is not an SSRI in that the drug is not selective just for serotonin, but also affects levels of dopamine and norepinephrine, two other neurotransmitters.
The first SSRI, Prozac (chemical name fluoxetine), came out in 1988. Five other SSRIs are now available in the United States: Paxil (paroxetine), Zoloft (sertraline), Luvox (fluvoxamine), Celexa (citalopram) and Lexapro (escitalopram).
Doctors say SSRIs not only work well to control depression, but have minimal side effects. Prior antidepressants had potentially severe side effects on blood pressure, heart rate, vision, weight and interactions with other drugs, Las Vegas psychiatrist Howard K. Mason notes. Lethal overdoses were also a risk.
And doctors today also prescribe SSRIs for a host of mood-related conditions besides depression: bipolar disorder, irritability, panic disorder, premenstrual syndrome, premenstrual dysphoric disorder, social anxiety disorder, post-traumatic stress disorder.
Still other conditions that are treated with SSRIs don't even seem, to a layman, to be mood-related: irritable-bowel syndrome, obsessive-compulsive disorder, anorexia nervosa and bulimia.
SSRIs might seem to be a silver bullet: powerful, versatile, few drawbacks. They are clearly popular.
In 1999, three of the 10 top-selling drugs of any sort in the United States were Prozac, Paxil and Zoloft. Sales of SSRIs are increasing about 25 percent a year. About one in eight adult Americans have taken an antidepressant in the past 10 years -- the decade that the SSRIs took hold. David Antonuccio and coauthors cited these numbers in a July 2002 article in Prevention and Treatment magazine. Antonuccio is a clinical psychologist at the University of Nevada School of Medicine.
It's almost impossible to overprescribe antidepressants, some local doctors maintain.
Patients regularly come to obstetrician-gynecologist Jozsef Zority requesting SSRIs. On the one hand, he screens each for anxiety-related symptoms before prescribing anything. On the other, he has never encountered a woman seeking SSRIs who did not turn out to be an appropriate candidate.
He did not prescribe antidepressants for patients before SSRIs came out. In the old days, he always sent depressed patients to specialists.
Zority dismisses the impact of direct marketing by drug companies to consumers, even though some come in asking him for a specific brand of SSRI. "That is our society," he says. "We have too much marketing about everything."
Dr. Francis Ellyin of Las Vegas, who is in family practice, often encounters mild depression and other mood disorders in patients who refuse to see a psychiatrist. He says SSRIs are an excellent treatment tool for them. Ellyin monitors some patients as young as 10 on SSRIs, but only after they have been evaluated by a specialist such as a psychiatrist or clinical psychologist.
Psychiatrist Mason puts the statistics on high use of SSRIs into perspective, emphasizing that depression rates also are high.
"One of every four women will have a clinically significant bout of depression, and one out of five men," he says research suggests. "To me, that's a lot of people that suffer needlessly" since research also suggests most depressed people do not seek diagnosis or treatment.
But critics of SSRIs still say the drug makers have overstated their power of their products, in part by massaging research data -- in ways that are acceptable to the U.S. Food and Drug Administration, which approves new drugs -- and in part by expert marketing.
One example of sleight of marketing is the repackaging of Prozac in 2000 as Sarafem. Prozac garnered some negative publicity, perhaps because it was the first SSRI, after some patients on Prozac committed violent acts. No cause-effect link was found between the Prozac and the behavior.
Chemically the same as Prozac, Sarafem got a new image with its name. Sarafem is geared for women with premenstrual mood symptoms such as depression or irritability.
"The Emperor's New Drugs" is what psychologist Irving Kirsch of the University of Connecticut calls SSRI antidepressants in a July 2002 issue of Prevention & Treatment.
He claims the new antidepressants are about 20 percent more effective than the inert placebo drugs against which they are compared.
Kirsch analyzed all the antidepressant medication data in the FDA's data base on the six most widely used drugs approved between 1987 and 1999. The data base covers all studies on the drugs, not just published studies. Drug makers routinely fail to play up results of studies that are inconclusive or unflattering to their products.
Antonuccio at the Nevada School of Medicine is another critic of SSRIs.
He cites a study that showed 12 weeks of psychotherapy was more effective than 12 weeks of antidepressants at treating depression. Therapy can equip a patient to deal with future life experiences, too -- with no side effects, Antonuccio adds. Patients who got therapy were half as likely to relapse as counterparts who only took medication, the study found.
"There are ... side effects, but I think there's a tendency to minimize them," Antonuccio warns. SSRI side effects can include agitation, sleep disruption, sexual dysfunction and gastrointestinal problems.
Some patients who, under a doctor's supervision, are tapering themselves off an SSRI encounter unpleasant discontinuation symptoms, Antonuccio adds. Many mistake the symptoms for a relapse of the original illness, so they return to the medication.
David Healy, a researcher in the United Kingdom, has even found evidence that SSRIs can induce suicidal thoughts in a small percentage of patients. "These are not benign effects," Antonuccio warns.
New research also is examining a link between breast cancer and SSRI use in women. "Correlation does not mean causation," Antonuccio admits. He argues for long-term studies of SSRIs, which have not been done. "Since 70 percent of antidepressants go to women, we need to figure this one out."
