For individuals whose depression is not alleviated by standard therapies, new depression treatment options are under investigation. At the forefront of research are various brain-stimulating techniques, such as deep brain stimulation (DBS), which involves the implantation of a device that delivers an electric current to the brain to normalize its activity. Like the heart, the brain is an electrical organ, so stimulating it with a small electrical current is an efficient way to precisely target areas that are malfunctioning —more efficient than drug therapy, in fact, which tends to affect the whole brain and often causes side effects.

Although results of small trials have been encouraging, the finer points of the procedure are still being debated: the precise areas of the brain to stimulate, the optimal number of electrodes to implant, and the voltages to use. DBS is also not without risks. It is, after all, brain surgery, which carries with it the chance of hemorrhage (excessive bleeding) in the brain, infection, and even death. The DBS device can malfunction, and the batteries typically need to be replaced after four to five years. In addition, doctors need to carefully monitor the multiple medications patients are typically taking to ensure that drug side effects and interactions are minimized.

Besides DBS, recent studies have shown that vagus nerve stimulation (VNS) may help people with treatment-resistant depression. A vagus nerve stimulator is a small, surgically implanted device designed to stimulate the brain periodically through the vagus nerve —a major nerve that passes from the brain through the neck and chest into the abdomen. One VNS device was approved in 2005 by the FDA for treatment-resistant depression.

Another treatment method under investigation is rapid transcranial magnetic stimulation (rTMS). In this technique, an electromagnetic coil is placed on the scalp (but not implanted). A high-intensity current passes through the coil and produces a powerful magnetic field that affects the function of the underlying brain cells. Some studies have shown that rTMS performed in the frontal areas of the brain can have antidepressant effects. One rTMS device was approved in 2008 by the FDA for treatment-resistant depression.

Additional drugs are also being tested for treating depression. These include drugs that stimulate the production of gamma-aminobutyric acid (GABA, a neurotransmitter that suppresses the action of nerve cells); medications that block the action of glutamate (a neurotransmitter that stimulates nerve cells); drugs that block substance P (a protein originally investigated for its role in pain); and blockers of corticotropin-releasing factor receptors, which play a role in the body’s reaction to stress.

Even the wrinkle fighter botulinum toxin (Botox) is under investigation. In one small preliminary trial of 10 women, it was injected into facial muscles to discourage frowning, resulting in a reduction in depressive symptoms.

Publication Review By: Karen L. Swartz, M.D.

Published: 07 Mar 2011

Last Modified: 22 Jun 2011