Individualized, Ultrabrief ECT Effective for Geriatric MDD

Liam Davenport

July 21, 2016

An individualized, ongoing electroconvulsive therapy (ECT) program, in combination with antidepressants, achieves sustained remission and prevents relapse in older patients with severe depression, new results from a two-phase study indicate.

Charles H. Kellner, MD, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, and colleagues initially administered right unilateral ultrabrief pulse ECT, which is designed to minimize cognitive effects, plus medication to patients aged 60 years and older who had severe depression.

A group of those patients who achieved remission were then randomly allocated either to stop ECT and continue only with medication or to carry on with ECT, with the dose adjusted on the basis of an algorithm that took into account treatment response, along with medication.

Results showed that more than 60% of patients achieved remission and that 70% had a response in the first phase of the study. Moreover, those who continued with ECT into phase 2 were more than six times more likely to be rated as having no illness than those who had received medication alone.

"The clinical implications of these findings are that continuing ECT after remission, rather than abruptly stopping a course of ECT, is likely to be beneficial in sustaining mood improvement for most patients, and that clinicians should be willing to prescribe additional ECT if patients begin to show symptom reemergence," the investigators write.

"The newer right unilateral ultrabrief pulse ECT technique allows practitioners to be more liberal in prescribing additional ECT when needed," they add.

They note that the data also show that "tapering a course of ECT and early intervention with additional ECT if symptoms worsen can prevent full syndromic relapse and its potentially catastrophic consequences."

The findings were published online July 15 in American Journal of Psychiatry.

Effective, Safe, Well-Tolerated

For the first phase of the study, the researchers recruited patients aged 60 years and older who had been diagnosed as having a unipolar major depressive episode and who had a score ≥21 on the Hamilton Depression Rating Scale (HAM-D). The patients were referred for ECT at eight US centers between 2009 and 2014.

Participants underwent dose-titration ECT until the seizure threshold was met. They then received ECT at six times the seizure threshold three times per week. Remission was assessed using the HAM-D three times per week. Remission was defined as the patient having a HAM-D score of ≤10 on two consecutive ratings, with the HAM-D score not increasing by more 3 points on the second consecutive rating or remaining at ≤6.

If, by week 6 of treatment, HAM-D scores decreased by more than 25%, the ECT stimulation dose was increased by 50%. The treatment dose was again increased by 50% if HAM-D scores decreased by more than 25% by week 9 of treatment.

In addition, the patients were started on open-label venlafaxine (multiple brands) up to 5 days before starting ECT, with a target dose of 225 mg/day. Treatment with venlafaxine was continued throughout the study.

The team reports that 172 of the 240 patients who entered phase 1 of the study completed it. The remission criteria were achieved by 148/240 (61.7%) patients; 24/240 (10%) did not achieve remission; 68/240 (28.3%) dropped out.

Among patients who achieved remission, the mean decrease in HAM-D score was 24.7 points. The mean final score was 6.2, and the average change from baseline was 79%. The mean number of ECT treatments required to achieve remission was 7.3.

Crucially, 169/140 (70.0%) patients met the response criterion, which was defined as a decrease of ≤50% from baseline in HAM-D score.

In phase 2, 120 patients who had achieved remission in phase 1 were randomly allocated to receive medication alone or ECT plus medication. Medication consisted of venlafaxine, administered at the same target dose that was used in phase 1, plus open-label lithium (multiple), at an initial dosage of 300 mg/day over 24 weeks.

The latter intervention comprised an initial fixed component of four ECT treatments over 1 month. This was followed by a flexible component in which use of ECT was determined by application of the Symptom-Titrated, Algorithm-Based Longitudinal ECT algorithm. Described by Sarah Lisanby, MD, and colleagues in 2008, this algorithm prescribes between zero and two ECT treatments in a given week, depending on the patient's HAM-D scores. Patients also received the medication on the schedule that was used in the medication-only arm of the study.

After 24 weeks of treatment, the ECT-plus-medication group had statistically significantly lower HAM-D scores than patients in the medication-only group, at a difference in adjusted mean HAM-D score at 24 weeks of 4.2 (P = .002). The analysis took into account study site and psychosis.

Patients treated with ECT plus medication were significantly more likely than those given medication alone to be rated as "not ill at all" on the Clinical Global Impressions severity scale at the study end, at an odds ratio of 5.2 (P = .009).

Patients treated with medication alone were 1.7 times more likely to experience relapse than those given ECT plus medication. There were no significant differences between the two groups in terms of Mini-Mental State Examination scores at 24 weeks.

Dr Kellner told Medscape Medical News, "This is very good evidence that [right unilateral ultrabrief pulse ECT] is an effective and safe and well-tolerated treatment for geriatric depression.

"It's been known before this study that ECT is the treatment of choice for the most severe forms of depressive illness. This adds further evidence that this particularly benign form of ECT is still quite effective, almost as effective as the other types of ECT technique, so that many people can be treated with this more modern ECT technique and get away with fewer side effects, and still do very well."

Dr Kellner added that the effect of the technique on the patients' cognitive status will be the subject of a further article, noting, "It's pretty clear from the rest of the literature that unilateral ultrabrief pulse ECT is cognitively quite benign.

"One of the big reasons that some practitioners are reluctant to prescribe ECT is because of concerns about cognitive effects, so this should encourage people to use ECT, because it is a very well-tolerated treatment, and many of these people are very severely ill.

"If treatment is denied or delayed, some of them will die by suicide, and even if they're not that severely ill, they will continue to suffer tremendously. So, my hope is that this will demonstrate that this is a reasonable therapeutic option that is quite benign," he said.

"Huge" Clinical Impact

Commenting on the findings for Medscape Medical News, Christopher C. Abbott, MD, Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, said that the results of the study, particularly from phase 2, are "really exciting" and are "going to have a huge clinical effect."

He noted that the risk for relapse after responding to ECT "is the biggest problem in the field.

"It's really scary when somebody does well, and then they start to relapse. How to prevent that is essential for the ECT clinician," he added.

"I think this paper really offers the absolute best guidance in order to minimize that risk."

Dr Abbott commented that although ECT is the "gold standard for any type of antidepressant treatment," there is a view that it is "a transitory phenomenon where we can get people well, but it's not going to be a sustained response."

However, the current findings "really reassure not only clinicians but patients alike that this is going to be a sustained response, and people can think very optimistically about an ECT series."

The study was supported by the National Institute of Mental Health. The original article provides a complete listing of the authors' financial relationships.

Am J Psychiatry. Published online July 15, 2016. Phase 1 abstract, Phase 2 abstract


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