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Low-energy devices tread lightly on the limbic system // Magnetic pulses feel as harmless as a haircut // Electrodes embedded deep within the brain help lift patients from profound depression.

Out of Despair

By Cathryn Delude // Summer 2006
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Karmen McGuffee used vagus nerve stimulation to treat her depression.

Catherine Ledner for Proto

Home free after years of severe depression, Karmen McGuffee credits vagus nerve stimulation, a controversial therapy.

She wasn’t strapped to a table and didn’t thrash in agony, as in the popular conception of this once-notorious treatment, and no massive bolt of electricity surged through the electrodes attached to her head. And although it ultimately failed to lift her spirits, at least the electroconvulsive therapy (ECT) that Mustafa Husain’s patient received for her severe depression wasn’t brutal. Patients today usually get general anesthesia and a muscle relaxant. Then a three-second pulse of current causes a 30-second seizure in the brain. Throughout the treatment, the patient remains almost motionless.

The usual course of treatment calls for six to eight out-patient sessions spread out over two to three weeks. After each session, the patient will likely feel disoriented and will stay in recovery for half an hour to become fully alert. She may not remember events just before and after the procedure. Some patients describe longer-term cognitive deficits, including memory loss, although studies have not been able to demonstrate these objectively.

Often, however, ECT works where other therapies have failed, and an estimated 100,000 people receive the treatment yearly. Husain, professor of psychiatry and internal medicine at the University of Texas Southwestern Medical Center, has often seen treatment-resistant patients respond well, and hoped it would help this patient, whom he had already treated with long courses of psychotropic drugs and psychotherapy. But ECT, too, failed to brighten his patient’s guilt-ridden gloom. “I did everything I could think of,” he says. “I changed the placement of the leads and the stimulus dosage, and used caffeine to lower her threshold. But she just didn’t improve much. Some patients don’t improve no matter what you do.”

Now, though, ECT-inspired treatment options are expanding. Several alternative brain stimulation devices have already entered clinical practice, and more are in clinical trials or research studies. The new tools come with their own acronyms—VNS for vagus nerve stimulation, rTMS for repetitive transcranial magnetic stimulation and DBS for deep brain stimulation—and their own distinctive approaches to correcting malfunctioning brain circuitry.

These brain stimulation devices, while expanding therapeutic options, are also changing the understanding of depression as a medical disorder, as researchers learn more about underlying abnormalities in the brain. “Before, we couldn’t establish direct links between brain location, brain function and behavior noninvasively. Now, we can use these tools to probe circuits to understand how the normal brain works, and what impact illnesses have on functional connections in the brain,” says Sarah Lisanby, director of the Brain Stimulation and Neuromodulation Division at Columbia University.

Major depressive disorder is often a lifelong, recurring condition that can sap vitality, hobble motivation, ruin relationships, derail careers, squelch libido, exaggerate anxiety, banish sleep and lead to suicide. It has such an eclectic appearance that two people may share the diagnosis but have few or no symptoms in common. Those varied manifestations of the disease may result from different malfunctions in the brain, and could explain why multiple patients may respond very differently to the same treatment.

Some patients benefit from talk therapy, but others require medications that restore a balance in the brain’s neurotransmitters, the chemicals that relay messages among neurons. Prozac and the other selective serotonin reuptake inhibitors (including Paxil, Zoloft and Celexa) effectively increase levels of the neurotransmitter serotonin by prolonging the process by which neurons take up the chemical after it has transmitted an impulse across a synapse.

Electrical brain stimulation, in contrast, targets the neural circuitry. Brain disorders, including depression, are thought to result when the electrical signals that travel through neural circuits are disrupted in a particular region. ECT induces a seizure that, in a way still not fully understood, resets the circuitry of large regions of the brain, possibly restoring the proper release and uptake of neurotransmitters. But in causing a seizure, ECT acts like a blunt instrument, sending a large current through the skull, basically to see what happens. Nonconvulsive devices hold promise because they attempt to achieve the same results by targeting a pivotal place, without inducing a seizure.

The new options are all variations on the ECT theme of using electricity to change the pattern of brain activity. Several of them work on specific regions of the brain that research has linked to abnormalities, and all stimulate the brain with lower doses of energy than ECT, and without causing seizures. Their efficacy depends on the brain’s plasticity, its ability to be remodeled by learning, experience, drugs—and electricity.

previous // next
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1. Magnetism on the Brain: Researchers Probe Transcranial Magnetic Stimulation, by Tracy Hampton. Medical News & Perspectives; JAMA, April 13, 2005. An overview of the history of transcranial magnetic stimulation and its therapeutic potential for depression and other conditions.

2. Deep Brain Stimulation for Treatment-Resistant Depression, by Helen S. Mayberg et al., Neuron, March 3, 2005. Report of findings that the subgenual cingulate region is metabolically overactive in treatment-resistant depression and that DBS applied to this region effected sustained remission in four of six patients.

3. VNS and depression: current status and future directions, by Sally P. Walsh and Mitchel A. Kling, Expert Review of Medical Devices, September 2004. A summary of research findings and the questions that still need to be addressed.

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