Pam Harrison

August 30, 2015

Amsterdam, The Netherlands — Updated findings from the Prolonging Remission in Depressed Elderly (PRIDE) study continue to support the use of right unilateral electrode placement and ultrabrief pulse stimuli as an optimal means of achieving a rapid response, and even remittance, within a week of delivering three courses of electroconvulsive therapy (ECT) in geriatric patients with major unipolar depression.

The findings were presented here at the 28th European College of Neuropsychopharmacology (ECNP) Congress.

"ECT remains a preferred treatment for older patients because it is still very safe, even for medically compromised patients, and many patients have trouble tolerating other treatments, including the antidepressants," Charles Kellner, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai in New York City, told Medscape Medical News.

"And while you should always individualize what you do for a patient based on how urgently ill they are, response rates to ECT are actually higher as patients get older," he said. "So ECT is a very powerful biological treatment for major depression, and with this type of ECT, you can induce seizures at a very low threshold, which is a major advantage."

Since earlier reports from PRIDE in 2013, approximately 240 patients have been enrolled in PRIDE, 173 of whom have completed phase 1 of the study.

A total of 148 phase 1 patients remitted after a thrice-weekly ECT ultrabrief regimen augmented with venlafaxine at a target dose of 225 mg a day.

On study entry, patients were, on average, 70 years of age and had a mean baseline Hamilton Rating Scale for Depression (HRSD24) of 31, a sign they were very ill.

In contrast, only 11% of the cohort was psychotic, which is relatively low for a trial in major depression.

Response criteria required a 50% decrease in HRSD24, whereas remission required a HRSD24 of 10 or less on two consecutive measurements.

At the end of phase 1, there was a 62% remission rate, some 10% of the participants were nonremitters, and 28% dropped out of the study.

In numerical terms, the HRSD24 dropped to approximately 6 at the end of the phase 1 trial, from a baseline score of 31, "so there was a highly significant, dramatic improvement in these patients," Dr Kellner observed.

Indeed, even when investigators evaluated both the nonremitters and the drop-outs, "most patients are getting some benefit from ECT, even if they do not meet our strict response or remission criteria," he added.

Response was also very rapid: 10% of responders achieved a 50% decrement in their HRSD24 after the first ECG treatment, "and I remind you that their first treatment was done at an ultralow dose to find the patient's seizure threshold," Dr Kellner observed.

Some 28% of responders achieved the same 50% decrement in their HRSD24 after the second treatment, and by the end of the week, 40% of patients had a 50% decrease in their HRSD24.

Eight percent of the cohort also achieved remission criteria after two treatments, Dr Kellner added, and 18% after three sessions, "and this in a subgroup of patients who have been very sick for a long time, who got remarkably better after a single week of ECT," Dr Kellner pointed out.

As expected, the small group of psychotic patients within the PRIDE cohort responded even better to ECT than the nonpsychotic patients, a finding that has been widely replicated.

The average number of ECT sessions it took to get responders well was 7.3 in PRIDE, but 20% of patients remitted in fewer than four sessions of ECT, and about three quarters of the cohort remitted within 3 weeks.

Nevertheless, Dr Kellner cautioned that there are patients who require more prolonged ECT.

"This speaks to the point that you can't tell a patient at the beginning of treatment exactly how many treatments they will need," Dr Kellner emphasized. "Patients should be treated until they are well, and some patients need a prolonged course of ECT."

As Dr Kellner reminded delegates, one of the most serious symptoms of patients with mood disorders is suicidality.

At baseline, more than 22% of patients scored high for suicidality, as measured by the third question of the HRSD24 scale.

By the end of the study, almost 85% of patients scored zero on the same scale, meaning there was no remaining suicidality among the great majority of PRIDE patients.

"In conclusion, right unilateral ECT is a viable treatment for geriatric depression, and it is rapidly acting, including on suicidality," Dr Kellner summed up.

"Patients also reorient very quickly after this type of ECT, and it looks as if they tolerate it cognitively extremely well," he said.

Detailed cognitive data from phase 1 and efficacy data from phase 2 are expected very soon.

Still Improving Delivery

Asked to comment on the use of ECT in general, and in the elderly in particular, session cochair William Nolan, MD, PhD. professor emeritus, University of Groningen, The Netherlands, told Medscape Medical News that more than 70 years after the discovery of ECT, it is surprising that researchers are still studying ways to improve its delivery, whether it should be given bilaterally or unilaterally and with what kind of current, how long to apply the stimulus, and whether ECT needs to be continued as maintenance therapy or whether patients should be switched to antidepressant agents, cognitive behavior therapy, or both, with the latter having been shown to prolong remission better than antidepressants alone in patients after achieving remission with ECT.

However, one of the biggest hurdles to the effective use of ECT remains its lingering stigma, he said. "I know that in the Netherlands, ECT was very stigmatized in the seventies," Dr Nolan said, "with only about 40 patients around that time per year receiving ECT."

At this time, ECT is much more widely used as patients and professionals begin to appreciate how effective — and how rapidly effective — treatment can be, as he suggested.

"ECT is not for every patient, of course. There are various forms of psychotherapy and medications that are much easier to use, as well as ketamine and various forms of intracranial stimulation, both of which work very rapidly as well," Dr Nolan observed.

"But the elderly are much more vulnerable to the side effects of antidepressant medication, so that's a good reason to use ECT in this patient group," he said.

"And it also produces a very quick response, which you want as well, because if geriatric patients stay depressed and immobile for too long, that also increases the risk of somatic complications."

Dr Kellner receives grant support from the National Institute of Mental Health, royalties from Cambridge University Press, and honoraria from UpToDate, Psychiatric Times, and North Shore-LIJ Health System. Dr Nolan has disclosed no relevant financial relationships.

28th European College of Neuropsychopharmacology (ECNP) Congress: Abstract S.05.04. Presented August 30, 2015.

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