PARIS (FRONTLINE MEDICAL NEWS) – Results of the randomized phase 2 portion of the landmark PRIDE study of electroconvulsive therapy for severe unipolar depression in geriatric patients hold a key message for clinicians, according to Charles H. Kellner, MD.

“The clinical take-home message is that practitioners should be liberal in prescribing additional ECT past the acute course. So our recommendation is that tapering ECT courses and being liberal with continuation and maintenance ECT should be adopted in clinical practice more widely with the aim of preventing full syndromic relapse and its catastrophic consequences,” Dr. Kellner said at the annual congress of the European College of Neuropsychopharmacology.

PRIDE (Prolonging Remission in Depressed Elderly) was a National Institute of Mental Health–sponsored nine-center study of right unilateral ultrabrief pulse ECT at 0.25 msec plus supportive pharmacotherapy for treatment of geriatric depression.

Phase 1 of the study involved 240 affected patients, 62% of whom achieved remission after receiving this form of ECT at six times the seizure threshold thrice weekly for up to 1 month coupled with low- or medium-dose venlafaxine. A mean of 7.3 ECT sessions were needed to attain remission as defined by a score of 10 or less on the Hamilton Rating Scale for Depression ( HAM-D24 ) on two consecutive occasions, down from a mean baseline score of 31.2. The scale was administered three times per week. Safety and tolerability of the ECT regimen were excellent, according to Dr. Kellner , chief of electroconvulsive therapy at New York Community Hospital and a psychiatrist at Mount Sinai School of Medicine in New York.

The PRIDE phase 1 data confirmed several points previously made in earlier studies. One is that the older patients are, the more ECT-responsive they are, even within an all-geriatric cohort such as PRIDE. Indeed, the remission rate was 55% in the 60- to 69-year-olds, compared with 72% in the 70- to 79-year-olds.

Another finding consistent with other studies: Patients with psychotic depression do particularly well with ECT. All PRIDE participants with psychotic depression achieved remission.

Also, ECT had a very rapid antisuicidal effect. At baseline, 24% of patients had a score of 1 on HAM-D24 item 3, which rates suicidality. An additional 34% had a baseline score of 2, 14% scored 3, and only 23% had a score of 0. After only a few weeks of ECT, however, 84% of patients had a score of 0 and 9% scored a 1.

“That’s one of the compelling clinical reasons to refer patients for ECT: This type of ECT is really good for treating suicidality,” Dr. Kellner noted.

Phase 2 was the more interesting part of the PRIDE study, he continued, because it evaluated in randomized fashion the efficacy and tolerability of a novel flexible, individualized strategy for as-needed maintenance ECT to sustain the mood improvement once remission was achieved. Dr. Kellner stressed that some form of maintenance therapy is essential post ECT-induced remission.

“It’s unreasonable to expect that ECT could cure the patients’ underlying illness and protect them from getting sick again for the rest of their lives. One has to understand this is a recurrent episodic illness that we’re treating. What ECT does is treat the current episode, and it does it better and more thoroughly than any other treatment in psychiatry,” Dr. Kellner said.

Post-ECT relapse rates are clearly higher in the modern era, which makes a compelling case for developing safe and effective maintenance strategies.

“We don’t quite understand why relapse rates are higher today. My belief is that for patients who come to ECT, their illness has been destabilized by having been on multiple trials of antidepressant medications beforehand. It may also be that the forms of ECT that we’re using today are somewhat less potent than the ones used in previous decades,” Dr. Kellner conceded.

He and his coinvestigators named their investigational maintenance ECT strategy STABLE, for Symptom-Titrated, Algorithm-Based Longitudinal ECT. It’s a complex algorithm described in detail in a published report ( Am J Psychiatry. 2016 Nov 1; 173[11]:1110-18 ). Basically, it consisted of four mandatory additional ECT sessions administered once weekly for the first month post remission, followed by either one, two, or no ECT sessions per week based upon evidence of deterioration as expressed in HAM-D24 scores.

In phase 2 of PRIDE, 128 remitters from phase 1 were continued on venlafaxine at a mean dose of 192 mg/day. In addition, they were placed on lithium, achieving a mean lithium level of 0.53 mEq/L, which Dr. Kellner deemed “low but reasonable.” These 128 patients were then randomized to the STABLE arm of flexibly administered ECT or to medication only and were followed prospectively for 6 months.

The primary endpoint was change in HAM-D24 score over the course of 6 months. From a baseline mean total score of 6, the mean score climbed to 8.4 in the medication-only group while dropping to 4.2 in the STABLE arm.

“At every time point along the way in the 6-month course of phase 2 of the illness, patients who were in the STABLE arm were less symptomatic and doing better than patients in the medication-only arm,” Dr. Kellner observed.

The key secondary efficacy outcome was change in the Clinical Global Impressions Severity scale. At follow-up, the patients in the flexible ECT plus medication arm were 5.2 times more likely to be rated “not ill at all” than were those on pharmacotherapy only.

In addition, relapse occurred in 20% of the medication-only group versus 13% in the STABLE group.

Global cognitive functioning as assessed by the Mini-Mental State Examination – crudely, in Dr. Kellner’s view – did not differ between the two groups at follow-up. Results of more sophisticated tests of multiple specific domains of cognition will be forthcoming.

Of note, two-thirds of patients in the STABLE arm required no additional ECT after their four continuation ECTs during the first month.

A swipe at ECT’s critics

Dr. Kellner called ECT “a fabulous therapy,” albeit one with a serious image problem.

“I think the problem with ECT is not that we don’t know all the details of how it works or what it does clinically, it’s really a sociopolitical issue about ECT not being adequately accepted. I break down this lack of acceptance into two forms: The first is passive lack of acceptance based on our profession not having embraced ECT and continuing to fail to embrace it. The other is the active propaganda against ECT that is promulgated by the Church of Scientology, which has taken on a life of its own now because of the Internet. ECT is still fought by the Church of Scientology. They fund lots of people to say incorrect nasty things about ECT to inappropriately frighten our patients,” Dr. Kellner charged.

He cautioned that proposed new Food and Drug Administration regulations governing ECT devices would greatly limit the use of ECT, restricting it to adults with treatment-resistant major depressive disorder or bipolar disorder or who require a rapid response. Other currently cleared indications would become off-label uses.

“With off-label ECT, the potential problem is practitioners may not be covered by their malpractice insurance. And the bigger issue is health insurers may not pay for it unless the ECT is for an on-label indication,” Dr. Kellner said.

He shared that he has found extremely helpful a colleague’s advice to demystify ECT by inviting a family member to witness a patient’s treatment session. That witness can then testify to others that what goes on bears no resemblance to what happens to Jack Nicholson in the classic film “ One Flew Over the Cuckoo’s Nest .”

The PRIDE study was funded by the National Institute of Mental Health. Dr. Kellner reported having no financial conflicts of interest.