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CNS Response has built a database of EEGs belonging to about 2,500 patients, from which it's possible to match certain abnormal brain patterns to improvement on a specific drug or combination. When a new patient submits an EEG, CNS Response compares it with their database to suggest personalized medication options (the company's technology is currently in clinical trials). Occasionally the recommendations are surprising. "I had a woman with alcohol dependence and anxiety along with low-level depression," says Mark Schiller, MD, an associate clinical professor of psychiatry at UCSF and the company's director of medical affairs. "The database showed she might respond to a combination of a mood stabilizing drug and a stimulant. Now she's much less anxious and more active. Without this test, I would not normally have tried these types of medications."

Diagnostic scanning is still very experimental, but Nobel Prize–winning neuroscientist Eric Kandel, MD, believes it's promising for gauging what kinds of psychotherapy would be most effective. "It's an important methodology for all aspects of psychiatric illness, and it's a major step forward," says Kandel, University Professor at Columbia.

Drugs: Beyond Prozac

Many new drugs are being investigated. One surprising candidate (except perhaps to certain club-hoppers) is ketamine, an anesthetic that's also sold on the street illegally under names such as Special K. In a recent trial, it snapped people out of depression almost instantly, unlike available medications that often take weeks to work. "We administered very low doses of ketamine intravenously and saw antidepressant effects in as early as two hours," says Husseini Manji, MD, director of the mood and anxiety disorders program at the National Institute of Mental Health. And these were patients who had tried, on average, six antidepressants without success; some even failed to improve with ECT. "By 24 hours, about 70 percent had responded to the ketamine and 35 percent met criteria for remission," says Manji. "It's remarkable that the drug works so well in this difficult-to-treat group, and one dose kept people well for a week."

Ketamine acts on receptors to a different neurotransmitter (glutamate) than current antidepressants do. The problem is that it affects parts of the brain not related to depression; the drug can also cause hallucinations (usually in higher doses—the reason people snort the powder or inject it to get high). "But if we can tweak it and make it in pill form," says Manji, "we might have a great medication that works fast and is easy to use."

Even more exciting to Manji, who thinks "we've been just scratching the surface by focusing on neurotransmitters," is the development of antidepressants based on molecules that travel inside nerve cells to adjust them. "This is a bit far off. But there was a study using the breast cancer drug tamoxifen to treat mania, mainly because it works inside the nerve cell, and it showed a remarkable and very rapid effect."

What all this research means for anyone who bumps up against depression is that soon there will be more options. For many people, psychotherapy and antidepressant medications—new and old—might be enough. If not, the next step could be a treatment using magnetic fields followed, if necessary, by ECT, Lisanby says. "And DBS has the potential of offering hope to people who are not responding to what medical science has to offer today." In the meantime, if you're having no luck with current treatments, check clinicaltrials.gov for the latest research as well as studies you might want to join.

Tim Jarvis is a freelance journalist living in Miami.

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