Miracle Drug, Poison or Placebo?
Modern antidepressants have been blamed for deadly shooting rampages and violent suicides. At the same time, they’ve been hailed as miracle drugs that transform baleful Eeyore-types into bouncing Tiggers.
Now a review of recent research claims that the effects of the drugs are only marginally different from those of placebos or sugar pills.
It seems impossible that the same substances in the same dosage ranges could simultaneously be poison, miracle drug and placebo. But the diversity of responses is remarkable—and it points to the possibilities and pitfalls of personalized medicine.
For example, Stacy*, a 48-year-old woman who works in public relations in Ohio, describes her experience with Zoloft like this: “It felt like water after being in the desert. It wasn't an experience of elation or anything bi-polar … I'm far happier, more confident, far more relaxed.”
Lisa*, a 33-year-old business consultant from Maryland, had experienced severe suicidal thoughts as early as kindergarten. She says of taking Effexor, “My entire life is different and I finally feel like a normal person with normal emotions. These days I can honestly say I am a happy, well adjusted person.”
But JoAnne*, a 35-year-old educator and dancer living in the Washington, D.C. area, reported that both Zoloft and Prozac produced muscle weakness and excessive sweating—and no benefits.
And Bernice*, a 53-year-old science journalist in California, described her experience with a Prozac-like antidepressant this way: “It made me feel disconnected from myself and my family, so that I no longer felt any empathy and did not really care what happened to them or to me. It was a terrifying sensation of flatness and I definitely felt depressed and hostile in a way that I had never felt before.”
Bizarre experiences abound as well: Bernice had “a vivid nightmare of being shot in the head,” and the sensation she felt of dripping blood did not immediately disappear on awakening. Others report elimination of sexual desire, weight loss, weight gain, heart palpitations and elevated blood pressure.
*not their real names
Same drug, different results
How can similar—or even identical—drugs have such different effects? The explanation sheds light on some of the key questions that complicate research on depression and emphasizes the need for a science of personalized medicine.
“These are average changes,” explains Richard Tranter, M.D., consultant psychiatrist with the North West Wales NHS Trust in Great Britain. “They may actually mask wide variations in how individuals are responding.”
“If you look at a large scale trial,” Tranter continues, “You may get a slight shift overall. That could mean on the whole, everyone is a little bit better compared to placebo but it could also mean that within the group, some did really, really well and some did OK and some got worse, but overall, it looks like a small shift in the right direction.”
Two other complications are noted by psychiatrist Peter Kramer, author of Listening to Prozac. First, early data—of the kind included in the meta-analysis which found antidepressants no better than placebo—often fails to show results for drugs that later prove very effective. “We have medications that show effectiveness in post-stroke depression, in the elderly with multiple brain lesions, in people with chronic, intractable depression. Why do they only not work in the early trials?” he asks.
Second, people get excellent care in clinical trials, which makes the placebo effect especially strong. This means it’s harder to show a difference, even if a drug works well. “We may be losing effective substances, not approving ineffective ones,” Kramer notes.
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