Electroconvulsive Therapy Lifts Depression, Sustains Remission in Older Adults

July 18, 2016 • Science Update

An individualized program of follow-up treatment with electroconvulsive therapy (ECT) combined with an antidepressant was effective in preventing relapse in patients 60 years and older who had had a successful initial course of treatment for severe depression. These findings add to evidence of the effectiveness and safety of ECT for depression treatment in this age group, and show, moreover, how ECT can be beneficial as a follow-up treatment to sustain recovery.

The Prolonging Remission in Depressed Elderly (PRIDE) study was a multi-center clinical trial aimed at comparing two strategies—one with, and one without ECT—for sustaining the effects of ECT treatment for depression in patients over 60. Effective and safe means of not only treating depression but sustaining recovery in the older population is an important public health need. Older Americans are the most rapidly growing segment of the U.S. population. Depression among older people is linked to disability and poorer health in those with other medical conditions like diabetes, stroke, and heart disease. While effective depression treatments exist, not all patients respond to those most commonly used—antidepressant medications and psychotherapy. There is a particular need for information specific to older patients about effective treatments, and how to prevent relapse after initial treatment.

The PRIDE study tested right unilateral ultrabrief ECT, a mode of delivery for ECT designed to minimize cognitive side-effects. In Phase 1 of the study, patients over 60 with depression received three ECT treatments per week combined with the antidepressant medication venlafaxine. Following treatment, of the 240 patients who entered the study, 62 percent met criteria for remission (a reduction to a score of 10 or less on a 24-item standard rating scale for depression, the Hamilton Depression Rating Scale). The mean number of ECT treatments to remission was 7.3 (half of patients who remitted had fewer treatments and half more than 7.3). Patients who had not remitted after 12 treatments, 10 percent of the participants, were considered nonremitters; 28 percent of those entering the trial dropped out before 12 treatments without having remitted.

In Phase 2 of the study, patients who had remitted in Phase 1 were randomly assigned to either a combination of venlafaxine and lithium, or venlafaxine with ECT. Participants receiving ECT had four treatments over one month, plus additional ECT as needed while receiving venlafaxine. Standard treatment with ECT involves a fixed schedule of follow-up treatment that may result in either over- or undertreating patients. The PRIDE investigators in the study tailored any follow-up ECT treatment to a patient’s symptom scores, administering ECT according to a set of predetermined symptom thresholds for treatment. After 24 weeks, patients in the ECT plus medication group had significantly lower symptom scores (a difference of 4.2 in mean scores). Of those in the medication only group, 20.3 percent relapsed while 13.1 percent of those in the ECT plus medication group relapsed.

Several factors, including the history of ECT use, its portrayal in the media, and concerns about side-effects such as memory loss and disorientation, have contributed to its being used largely as a treatment of last resort. In addition to tracking the impact of treatment on depression, the investigators monitored cognitive function of all patients at each twice-monthly clinic visit. There were no statistically significant differences in scores on a mental status examination that addresses orientation, memory, attention, and the ability to follow verbal and written instructions. Study follow-up continued for six months. The authors also note that remission rates in this study are about twice that observed with antidepressant medications in similar age groups. The relatively rapid effect of ECT—the mean of 7.3 treatments to remission spans about 2.5 weeks—can not only make a difference in quality of life but is potentially important in instances in which a person with depression is contemplating suicide and the need for immediate, effective relief from symptoms is urgent.

Concerns about ECT’s effect on cognition and memory have prompted exploration of alternative methods of administering ECT, including the approach used here, right unilateral ultrabrief ECT. Previous research has reported that this method preserves the effectiveness of ECT while reducing side effects. One caveat offered by the authors was that the most severely ill patients would not have been able to participate in the study as participation required written informed consent for the research and the use of ECT. Nonetheless, this study helps fill the gap in research on use of ECT in older age groups for which there has been much less treatment effectiveness research carried out than in younger populations.

“The PRIDE study demonstrates that continuing ECT treatment following remission in a manner that is responsive to the needs of individual patients can maintain relief from depression and at the same time, avoid overtreatment,” said Sarah H. Lisanby, M.D., Duke University School of Medicine and senior author (Dr. Lisanby is now director of NIMH’s Division of Translational Research). “For older persons with depression, many of whom do not respond to other treatments, PRIDE offers information in support of ECT as an effective and safe option for both initial and maintenance treatment.”

The following centers recruited patients for the PRIDE study: the Icahn School of Medicine at Mt. Sinai, New York; Columbia University/New York State Psychiatric Institute, New York; Duke University School of Medicine, Durham, N.C.; Zucker Hillside Hospital/Northwell Health System, New York; Mayo Clinic, Rochester, Minn.; University of Texas Southwestern Medical Center, Dallas; Wake Forest University Medical Center, Winston-Salem, N.C.; Augusta University/Medical College of Georgia, Augusta; and New York Presbyterian/Weill Cornell Medical Center, New York and White Plains.

References

Kellner CH et al, the CORE/PRIDE Work Group. Right Unilateral Ultrabrief Pulse ECT in Geriatric Depression: Phase 1 of the PRIDE Study.  Published online July 15, 2016. http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2016.15081101

Kellner CH et al, the CORE/PRIDE Work Group. A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study.  Published online July 15, 2016. http://dx.doi.org/10.1176/appi.ajp.2016.16010118

Clinical Trial ID

NCT01028508

Grant

U01MH055495, U01MH081362, U01MH086127, U01MH086130, U01MH86120, U01MH084241, U01MH086122