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The Perfect Marriage: Science Begins To Explain Why Antidepressants and Talk Therapy Go Hand in Hand

on December 28, 2011

From http://www.forbes.com/sites/alicegwalton/2011/12/26/the-perfect-marriage-science-begins-to-explain-why-antidepressants-and-talk-therapy-go-hand-in-hand/

By Alice G. Walton

12/26/2011 @ 11:13AM

Antidepressants have been used for a number of years to treat mood disorders like depression and anxiety, and we’re relying on them more and more as the go-to treatment. This being the case, researchers know oddly little about how they work – or, more specifically, why they work. Another mystery is why when paired together, antidepressants and talk therapy are so much more effective than either method alone. Now, a new study may explain why the marriage is so successful.

What we do know about how antidepressants function is that they help increase the amount of neurotransmitter between nerve cells. The problem is it that this doesn’t necessarily translate into the behavioral changes that can follow. Some newer evidence has suggested that depression is linked to brain inflammation and/or the destruction of neurons, and that the reason that antidepressants (and exercise, for that matter) work is that they foster the growth of new nerve cells.

According to a new study, antidepressants may indeed set the brain back to a more “plastic” or youthful state, so that the stage is set for talk therapy to work its magic.

The researchers looked at how the antidepressant drug fluoxetine (Prozac®) affected the stress responses of mice. It’s been known for some time that fluoxetine may make certain parts of the brain more plastic, so the researchers wagered that the drug may also affect areas of the brain important in learning about stressful and non-stressful situations.

To test this idea in mice, first the researchers paired a tone with a painful shock to the feet (a la Pavlov). It doesn’t take many trials for mice to freeze whenever they hear the tone alone, in expectation of a shock; and these mice did just that.

But after this pairing, the researchers set out to “extinguish” the link by playing the tone without the shock. Adult mice are notoriously poor at unlearning the connection once it’s formed: even if they stop reacting to it somewhat, just one more pairing can send them right back into freeze mode. Young mice, on the other hand, are much more adaptable to this extinction training, and have almost no trouble unlearning the association.

As the researchers suspected, mice who were given fluoxetine during extinction behaved much more like young mice, in the ease with which they stopped reacting to the tone. And when they were reintroduced to the shock later on, they weren’t so quick to fall back on their previously stressed behavior. On the other hand, mice who were not given fluoxetine “renewed” their fear response much more quickly upon getting shocked again.

So, if adult mice given fluoxetine behave more like young mice in how quickly they can learn and unlearn new relationships in their environment, what’s going on the brain to explain these behavioral changes?

The brains of the mice who were treated with fluoxetine also looked “younger,” particularly in the cells in their amygdalas, the area of the brain that governs the fear response. One type of cell-adhesion molecule, normally expressed in younger cortical neurons, was more abundant in the mice who had been given fluoxetine. And a protein that normally increases as an animal ages existed in lower levels in the fluoxetine-treated mice. Other changes also indicated that the fluoxetine-treated brain had taken on a “development-like plasticity.”

If the mouse brain is acting like it’s younger, more plastic, more open to new experiences when it’s bathed in antidepressants, what does this mean for human beings battling depression? It could mean that antidepressants help set up the brain to be more receptive to the changes that psychotherapy can bring about. A more youthful-acting brain could be more sensitive to the methods used in therapy: learning new ways to cope, dealing with stressors, and instituting new thought patterns could take root more easily in a more plastic brain.

This study is important since it’s really the first to take a stab at an explanation for the why drug-psychotherapy combo is more effective than either method alone. Theoretically, the explanation makes a lot of sense, but more research will need to be done to explore the mechanism more fully – especially in humans.

Concerns have long been raised about why antidepressants don’t work in some people or actually have a negative effect, as well their efficacy compared to placebo and the higher likelihood of relapse that is associated with them. Understanding more about how antidepressants work in the brain is critical, given the number of people on them, and the fact that there are so many unanswered questions about them.

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