David Antonuccio, professor of psychiatry and behavioral sciences. Photo by Jean Dixon

David Antonuccio, professor of psychiatry and behavioral sciences. Photo by Jean Dixon

Antonuccio's research questions antidepressant efficacy

1/12/04 - David Antonuccio has some remarkable things to say about the drug industry and, in particular, the efficacy of its number one product: antidepressants. In a nutshell, the University of Nevada School of Medicine professor of psychiatry and behavioral sciences says: antidepressant drug effects may be far smaller than touted and side effects far greater; there’s no persuasive evidence that a deficiency of brain serotonin causes depression (the rationale for using most antidepressants); financial and political interests have biased research and medical education; and psychotherapy appears to be as effective as antidepressants in treating depression and even better at preventing relapse.

In an article in the December issue of the journal American Psychologist, co-written with School of Medicine colleague William Danton and Terry Michael McClanahan of Permanente Medical Group, Antonuccio details the extent of the pharmaceutical industry’s influence on medicine and proposes practical steps that could be taken to preserve the credibility and integrity of scientific research.

“I don’t think the word has gotten out about this wealth of data showing the small advantage of these medications,” Antonuccio said. “People tend to discount things they don’t want to believe. I think it’s a pretty common phenomenon, even in academic settings.”

For example, Antonuccio said somewhere between 20 percent and 35 percent of antidepressant studies are not published, and of those, it looks like as many as 90 percent may have unfavorable or neutral results.

In other words, the many studies that don’t show antidepressants work better than a placebo get buried by the drug companies. Antonuccio is able to track these unpublished studies through the Food and Drug Administration’s database. The FDA requires submission of all research data, but doesn’t require publication. Data analysis such as this is Antonuccio’s stock in trade.

“My role has become summarizing other people’s research, particularly comparative studies and educating the public about these data,” he said.

His conclusions, although based on meticulously documented analysis – often drawn from drug companies’ own data – are not always welcomed, even within his own profession.

“One of the reasons might be that the beliefs that are challenged by the data I present are strongly held and it’s upsetting that things might be different than people have believed for so long,” he said. “Fortunately, I work in a department and at a medical school that celebrates scientific curiosity and intellectual diversity.”

Antidepressants are a good example. They are the top selling drug category, with as many as one in eight adult Americans having taken one in the last 10 years. An estimated 3.5 billion doses of selective serotonin reuptake inhibitors (SSRIs) were consumed in 1999 alone.

“One of the theories is that depression is a chemical imbalance,” Antonuccio said. “But, serotonin theories have not been proven and they haven’t held up. There’s no convincing data that show any sort of biological imbalance causes depression. That’s not to say there are not chemical changes associated with depression and there may be immune system changes. We have to carefully think about making the logical leap that because something is associated with depression or anxiety, it is actually the cause of it.”

In fact, Antonuccio said, the causes of depression are not known. One theory is that it may be a defense mechanism that lets people know something needs changing in their lives.

“It might be a feedback system that lets us know something is out of whack, the same way that pain is when you touch something hot,” he said. “Certain kinds of thinking strategies may be more likely to lead to depression. Common ones include perfectionistic thinking, catastrophizing and overgeneralization.”

Although Antonuccio believes psychological therapies work at least as well as antidepressants, without the side effects, his key message is that consumers have a choice of treatments.

“It’s important for consumers to understand that because they too often think their only choice is medications,” he said.

Although antidepressants do have some success, the reason for that is unclear, Antonuccio said. It could be largely due to the placebo effect.

“Placebo is often taken to mean that something is not very effective,” he said. “Well, placebo is psychological and the psychological effects are powerful.”

Antonuccio got calls from media around the world, including CNN and Good Morning America, after his 1995 comparative review showing psychosocial interventions were as effective as antidepressants.

“The consistency of the results surprised us,” he said. “Apparently, it surprised the media, too. It fundamentally counterbalanced the popular beliefs about how effective these medications were. I believe it continues to be news because I don’t think the word has gotten out.”

Antonuccio advocates building a “firewall” between science and marketing that would: disclose conflicts of interest; prohibit drug industry advertising in scientific journals; prohibit continuing education credit for training underwritten by the drug industry; prohibit gifts from drug companies; prohibit drug company contact with patients or patient data; and implement procedures for protecting the integrity of research, such as documentation of concurrent treatments and allowing researchers independent data access. In short, he proposes moral and ethical guidelines to combat the widespread financial connections that he believes constitute a conflict of interest and compromise good science.

“I think we have to look closely at all industry funded research,” he said.


Antonuccio’s tips for someone with depression

·Be aware you have choices: psychosocial therapy alone; medication alone; a combination of both treatments. Be sure to consult your doctor before making any changes in medication.

·To learn more about the cognitive behavioral approach to treating depression, Antonuccio recommends reading David Burns’ Feeling Good, particularly chapter three, which lists common distorted thinking patterns that depressed people engage in.

·Put pleasant activities back in your life. Depressed people stop doing the things that used to be fun. Research has shown that this is an effective intervention in and of itself. Be sure to include exercise, which also has a positive effect on people with depression.

By John Wheeler, (775) 784-1581; jwheeler@adv.unr.edu

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