Miracle Drug, Poison or Placebo? Part III

Here is the conclusion of the 3 part article by Maia Szalavitz. Part III:

Other Factors

Unfortunately, most of these results failed to be replicated when researchers looked for them again. “People find predictors of response all the time but they are almost never replicated,” says Roy Perlis, M.D., an assistant professor of psychiatry at Harvard Medical School.

Genetic diversity may complicate the story. For example, one gene associated with positive response to antidepressants in whites was associated with lack of response in Japanese and Korean people.

The environment matters too—one study found that people who had been abused in childhood were less likely to respond to medicationsand more likely to be helped by talk therapy.

To complicate matters even further, it’s not just brain genes that affect drug response, but also a system of enzymes in the liver in which there is also great genetic variation.

For example, the enzyme CYP450 2D6 metabolizes Prozac and some related drugs and there are numerous variants of this one enzyme alone that can affect the way these drugs work. People whose 2D6 breaks down Prozac too fast may get no effect from ordinary dosages of the drug. Conversely, those whose enzyme works slowly may have severe side effects even at low dosages. A genetic test that is now commercially available can determine which variant someone has— but there’s another wrinkle.

Dietary factors significantly affect the actions of various enzymes. You may have heard of grapefruit juice negatively affecting the impact of drugs, but char-broiled meat, broccoli, star fruit, alcohol and tobacco also affect the response to medications. In addition, interactions between numerous medications can make things even less predictable.

“For the majority of people, these tests are not useful for antidepressant prescribing,” Perlis concludes. However, for people with bipolar disorder or psychotic depression who use antipsychotic medications, the tests can be important, particularly in terms of preventing serious side effects.

“It’s a nice idea,” concludes Tranter. “A lot of people are very interested in using genetics to predict the response to medication, but it’s too early to know what it will yield.”

Treating Depression Step By Step

But although trial and error and doctors’ clinical intuition are still all we really have to go on in antidepressant choice, a large study examining treatment of depression in real-world practice found that most people did benefit significantly by the end of the trial. Unlike a clinical trial, which usually just compares a drug to placebo or another drug, this trial involved trying different drugs sequentially if the first ones didn’t work for particular patients.

“Two-thirds got better by the end of the steps,” says Madhukar Trivedi, M.D., professor of psychiatry at the University of Texas Southwestern Medical School. “And by better, I mean that almost all the symptoms were gone—they were in remission. Not just showing improvement.”