Of course, even the best medications are often not enough to combat severe depression—for which psychotherapy is also an important part of the recommended treatment. The trouble is, many patients never get therapy. "In many communities, there is a shortage of trained therapists," says Jesse Wright, MD, PhD, director of the University of Louisville Depression Center in Kentucky. "And therapy can be expensive. But in the future, a computer may help solve these problems."

In computer-assisted therapy, or CAT, sessions with a human therapist are supplemented with the use of interactive software. The computer might show you a video of a woman who is depressed and demonstrate how her low mood is perpetuated by her excessively negative thoughts. The program would help you identify these types of thoughts in your own life, and lead you through exercises designed to get you thinking more clearly and positively.

Computers may also help doctors screen people at risk for depression, via voice analysis software that gauges a patient's mental state based on nuances of her speech. "Depressed people tend to talk in characteristic ways; their speech is quiet, slow, without a lot of variety or emphasis," explains Alex Pentland, PhD, a professor at MIT who helped develop the software. After analyzing thousands of samples of depressed patients' speech, Pentland and his colleagues created a program that recognizes cues only a very experienced clinician would pick up. He predicts that the software will one day be used to "listen over the shoulder" of healthcare providers on phone calls with patients, issuing an alert when it identifies the warning signs of depression.

For many patients whose depression doesn't respond to medication or therapy, the treatment of last resort was once electroconvulsive therapy (ECT). While effective, ECT can cause serious side effects, including memory loss. But a new generation of brain stimulation therapies is beginning to offer relief from intractable depression with fewer risks. "In the same way that cardiologists use pacemakers to correct abnormal heart rhythms, we're now beginning to use brain stimulators to correct the neural circuitry that's causing the psychiatric disorder," says Sarah Lisanby, MD, director of the Brain Stimulation and Therapeutic Modulation Division at Columbia University Medical Center in New York.

One therapy offered at Lisanby's clinic is transcranial magnetic stimulation (TMS). TMS delivers mild, painless electrical signals to the prefrontal cortex through a plastic-coated wire coil placed on the head. "The treatments stimulate nerve cells in a region of the brain called the prefrontal cortex," says Lisanby. "This area plays an important role in mood regulation, and it's often less active in people who are depressed." Scientists are also exploring how similar but more invasive technologies—such as vagus nerve stimulation and deep brain stimulation—might also be effective in alleviating treatment-resistant depression.

"In the past, our options for people with the most severe forms of the disease were very limited, but we're already able to offer a wider variety of safer choices," says Lisanby. For patients who have lived with the darkness of depression, such treatments will mean a bright new day.

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