Harvard Mental Health Letter

Why electroconvulsive therapy may be the best alternative to medication.

 Although medications and psychotherapy are usually the first treatments offered to patients with major depression, they don't work for everyone. As we reported in August 2008, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study found that about one-third of patients were unable to achieve full relief of symptoms (remission) even after trying four different strategies.

But the STAR*D data on relapse rates suggest that treatment-resistant depression may be even more common than remission rates might indicate. Relapse was a significant problem at each treatment level. By the end of the study, 50% of the patients who were able to achieve remission after trying a fourth treatment ended up relapsing within an average of 2.5 months.

By taking both relapse and remission rates into account for the entire study, Dr. J. Craig Nelson, an expert in treatment-resistant depression at the University of California, San Francisco, estimated that only 43% of patients enrolled in STAR*D were able to sustain their recovery. Other commentators have estimated that recovery rates may be even lower.

Thus, for treatment-resistant depression, clinicians remain interested in nonpharmacological ways to change brain function. Two FDA-approved options now exist: electroconvulsive therapy (ECT) and vagus nerve stimulation (VNS). In October 2008 the FDA also approved transcranial magnetic stimulation (TMS) for patients with depression who have not benefited from one antidepressant, but not for those who haven't responded to multiple drugs.

Insurers have balked at paying for VNS because it has not proven any more effective than ECT -- and they may also refuse to pay for TMS. Therefore, ECT remains the most practical alternative because it is effective, covered by health insurance, and readily available.

ECT at a glance Although ECT is often regarded as a treatment of last resort, it is probably the most powerful tool available to treat depression. Misconceptions and stigma about ECT may explain why it is not used more often. Here's a brief review of current ECT practice and several remaining challenges.

Who might benefit. ECT is an option for any patient whose depression has not been relieved after trying three or more distinct drugs; for patients at risk for suicide (ECT works faster and more reliably than drugs); for women who are pregnant or have just given birth who don't want to take antidepressants; and for elderly patients who either don't respond to drugs as well as they used to, or who, with age, have become more sensitive to side effects.

Although ECT has been used in children and adolescents, the technique has not been well studied in this population. The American Academy of Child and Adolescent Psychiatry has produced guidelines for ECT treatment of adolescents, recommending that it be considered after a patient does not respond to two or more medications, or when symptoms are so severe that fast treatment is necessary.

How it works. Before each treatment, the patient receives a short-acting anesthetic to prevent awareness of the procedure and to reduce discomfort. Other drugs are given to relax the muscles. While the patient is sleeping, the psychiatrist uses a special device to deliver an electrical impulse that stimulates the brain and causes a seizure. There are no outward signs of this seizure, but the doctor can watch it on a monitor (similar to an electroencephalogram) that measures electrical activity of the brain.

The mechanism of ECT action is not understood, but the seizure seems to restore the brain's ability to regulate mood. It may enhance the transmission of chemical signals or improve blood flow to the brain; animal studies suggest it may stimulate the creation of new brain cells. It is the seizure (not the electrical stimulus) that generates improvement.

Duration. Therapy usually consists of three ECT sessions a week, for a total of six to 12 treatments.

Side effects. The most bothersome side effects are memory problems and difficulty concentrating, although certain ECT techniques may help reduce risk. Other side effects -- partly from the anesthetic -- include headache and nausea.

ECT remission and relapse rates

Study Patients achieving remission with ECT Relapse rates at 6 months, with various maintenance therapies

Consortium for Research in ECT (CORE) 86% Nortriptyline (Aventyl, Pamelor) and lithium 32%

ECT 37%

Columbia University Consortium (CUC) 55% Placebo 84%