PARIS (FRONTLINE MEDICAL NEWS) Older patients with a psychotic depression and complete remission within the first four electroconvulsive therapy sessions are the ones with the best chance of remaining relapse free for at least 6 months, Pascal Sienaert, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

This conclusion is based on the results of two prospective studies by ResPECT – the Research in Psychiatry and ECT by the Flemish-Dutch Research Consortium – which, in turn, confirm the findings of an earlier metaanalysis of 32 studies including 702 patients conducted by investigators at Trinity College Dublin, noted Dr. Sienaert, a psychiatrist at the Catholic University of Leuven (Belgium) Academic Center for ECT and Neuromodulation.

That being said, it’s now clear that adequate maintenance therapy after successful ECT is the best way to reduce the risk of relapse, he said. The metaanalysis showed that continued use of antidepressant medications after successful ECT halved the 6-month risk of relapse, with an impressive number needed to treat of 3.3. Yet, the 12-month risk of relapse remained substantial, at 51%, and the Irish investigators stressed that maintenance treatment strategies need to be improved ( Neuropsychopharmacology. 2013 Nov;38[12]:2467-74 ).

Dr. Sienaert noted that the relapse rate in the ECT metaanalysis is nearly identical to that reported in the landmark Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) trial in real-world patients with major depression who achieved remission in response to second-step or later antidepressant medication.

“It’s a common misconception that relapse is higher after ECT than medication,” the psychiatrist said.

In the ECT metaanalysis, continuation ECT after induction of remission did not substantially affect the relapse risk. But that’s because the prevailing maintenance ECT strategy in the studies included in the 2013 metaanalysis relied upon a fixed-dose treatment schedule, according to Dr. Sienaert.

“In most studies, fixed-schedule maintenance ECT is used and with rather high relapse rates. Most clinicians have the experience that flexible, clinically driven on an as-needed-basis maintenance ECT has lower relapse rates,” he said. “Still, relapse remains the most pressing issue in the field, and it is very difficult for us as clinicians to predict which patients will relapse and which will not.”

That’s where the two ResPECT studies come into play.

In one of the studies, 116 patients with major depression at three tertiary psychiatric hospitals were randomized double blind to twice-weekly high-dose ultrabrief pulse (0.3-0.4 milliseconds) right unilateral or high-dose brief pulse (1.0 millisecond) right unilateral ECT. The dosing was at eight times the seizure threshold until remission as defined by a Montgomery-Åsberg Depression Rating Scale ( MADRS ) score below 10 or for a maximum of 6 weeks. Among the 87 completers, the remission rate was 68% in the brief pulse group, significantly higher than the 49% rate with ultrabrief ECT. Cognitive effects on semantic and lexical memory, and retrograde amnesia were the same in the two groups ( J Clin Psychiatry. 2013 Nov;74[11]:e1029-36 ).

Dr. Sienaert and his coinvestigators then prospectively followed the 50 remitters for 6 months, during which all but one patient remained on antidepressant medication. The relapse rate, defined as rehospitalization for depression, restart of ECT, suicide, or a MADRS score above 15, was 25% at 3 months and about 40% at 6 months. The investigators found several predictors of a lower relapse rate. The strongest was early complete remission as defined by a Clinical Global Impressions Scale score of 1 out of a maximum of a possible 7 points within the first four ECT sessions: The 6-month relapse rate was 10% among those early complete remitters versus 63% in the other remitters ( J Affect Disord. 2015 Sep 15;184:137-44 ).

“These are very small numbers in these groups, but the signal that emerges is the same as we have seen in the Irish metaanalysis: Early complete remitters were older, had shorter current episodes of depression, and showed more baseline psychotic features,” Dr. Sienaert said.

In a more recent ResPECT consortium study, the Mood Disorders in Elderly Treated With ECT (MODECT) study, 110 patients aged 55 and older with unipolar depression treated by ECT were followed with serial brain imaging studies prior to and for 6 months post treatment in an effort to gain insight into the mechanism of the particularly strong benefit of ECT in late-life depression. The response rate to ECT was significantly higher in those with onset of depression at age 55 or older than in those with disease onset before age 55, by a margin of 87% vs. 67%. The presence of baseline psychotic symptoms also was associated with a higher response rate.

In contrast, treatment response proved unrelated to changes in hippocampal volume, white matter hypersensitivities, amyloid load, or serum brain-derived neurotrophic factor, which is believed to be an important mediator of neuroplasticity. Thus, ECT’s mechanism of action in late-life depression remains elusive, the authors reported ( Am J Geriatr Psychiatry. 2017 Feb;25[2]:178-89 ).

In a separate study, Dr. Sienaert and his colleagues found that ECT’s superior efficacy, compared with antidepressant medication in patients with late-life depression, was independent of their vascular disease burden. The study population was comprised of 81 patients in an antidepressant drug trial and 43 in an ECT trial, all of whom were inpatients with unipolar major depression. Their mean age was in the mid-70s.

The investigators gauged vascular burden by adding up each patient’s number of vascular risk factors, namely, diabetes, hypertension, smoking, hypercholesterolemia, known cardiovascular disease, and cerebrovascular disease. The depression remission rate was 80% in the ECT patients with no vascular risk factors, dropping to 58% in those with one or more. In the antidepressant drug trial participants, the remission rate was 38% in those with no vascular risk factors, compared with 32% in patients with one or more. Using different cutoffs for the number of vascular risk factors did not significantly alter the results (Int J Geriatr Psychiatry. 2017 Jun 28. doi: 10.1002/gps.4754 ).

At present, once a patient has achieved remission in response to ECT, most psychiatrists stop the therapy altogether. That’s often a mistake, according to session cochair Eduard Vieta , MD, PhD.

ECT is the only treatment where people expect that it works acutely, and then we can stop it and nothing happens. That’s too much to expect. In many cases you need to continue ECT. Especially in patients who are refractory or treatment resistant, I don’t see a reason why maintenance ECT shouldn’t be the first choice. Yet in the guidelines, ECT is always the third- or fourth-line therapy,” said Dr. Vieta, professor of psychiatry at the University of Barcelona and scientific director of the Spanish Research Network on Mental Diseases.

Dr. Sienaert concurred, adding that he has patients who are on weekly maintenance ECT for as long as 16 years, with continued good results.

He reported having received honoraria from Mecta, a manufacturer of ECT equipment.