Is it Prozac? Or Placebo?
New research suggests that the miracles promised by antidepressants may be largely due to the placebo effect. Too bad there's no money to be made in sugar pills.
Janis Schonfeld recalls the events that started her on her recovery from 30 years of depression with snapshot clarity: the newspaper ad she saw in 1997 seeking subjects for an antidepressant study; the chair she was sitting in when she called UCLA's Neuropsychiatric Institute; the window she was looking out of when she first spoke with Michelle Abrams, the research nurse who shepherded her through the trial. She remembers being both nervous and hopeful when she arrived at the institute, and a little uncomfortable when a technician put gel on her head, attached a nylon cap shot through with electrodes, and recorded her brain activity for 45 minutes. But most of all she remembers getting the bottle of her new pills in a brown paper bag from the hospital pharmacy. "I was so excited," she told me. "I couldn't wait to get started on them."
Within a couple of weeks, Schonfeld, then a 46-year-old interior designer, got quickly and dramatically better, able once again to care for herself and her husband and daughter, no longer so convinced of her own worthlessness that she'd consider killing herself. For the next two months, she came back weekly for more interviews and tests and EEGs. And by the end of the study, Schonfeld seemed to be yet another person who owed a nearly miraculous recovery to the new generation of antidepressants -- in this case, venlafaxine, better known as Effexor.
But during her final visit to the institute, one of the doctors directing the research sat her down to deliver some disturbing news. "He told me I hadn't been taking a medicine at all. I'd been on a placebo. I was totally shocked." So was nurse Abrams. Both women knew that half the test subjects were getting placebos and that Schonfeld might be among them. But not only was she feeling better -- she'd even experienced nausea, a side effect commonly associated with Effexor, so they had each assumed that she was in the drug group. Schonfeld was so certain of this that at first she didn't believe the doctor. "I said to him, 'Are you sure? Check those records again.'" But there was no doubt. The brown bag contained nothing but sugar pills. Which didn't mean, he was quick to add, that she was making anything up, but only that her improvement couldn't possibly be due to the pharmacological effects of the pills.
Schonfeld's experience is hardly unique, although you wouldn't know it from the ubiquitous advertisements for antidepressants -- nor, if you were a doctor, would you know just how common it is from reading the medical journals. Psychiatrists and other mental-health professionals (I am a practicing therapist) know that any given antidepressant has only about a 50 percent chance of working with any given person. But what most people -- patients and clinicians alike -- don't know is that in more than half of the 47 trials used by the Food and Drug Administration to approve the six leading antidepressants on the market, the drugs failed to outperform sugar pills, and in the trials that were successful, the advantage of drugs over placebo was slight. As it would hardly help drug sales, pharmaceutical companies don't publish unsuccessful trials, so University of Connecticut psychology professor Irving Kirsch and his co-authors used the Freedom of Information Act to extract the data from the FDA. What they found has led them, and other researchers who've investigated antidepressants' relatively poor showing against placebos, to conclude that millions of people may be spending billions of dollars on medicines that owe their popularity as much to clever marketing as to chemistry, and suffering serious side effects -- not to mention becoming dependent on drugs for healing they might be able to do without them -- in the bargain.
But many doctors remain convinced that antidepressants do work, that the flaw lies not in the capsules themselves but in the studies used to evaluate them. Clinical trials can consume half a drug's patent life. And so pressure to bring the medicine to market leads researchers to adopt strategies -- such as recruiting people whose depression is too mild to yield powerful results -- better suited to clearing regulatory hurdles than generating useful scientific knowledge. That, and not the power of suggestion, is why antidepressants barely outperform placebos, these scientists say.
Gary Greenberg is a psyschotherapist and professor of psychology. His writing on medicine and science has appeared in the New Yorker, Discover, Rolling Stone, and McSweeny's, and is featured in Best American Science and Nature Writing 2002.