Ketamine, ECT Combo for Late-Life Depression: Mixed Results

Nancy A. Melville

April 12, 2017

DALLAS – The adjunctive use of the anesthetic ketamine with electroconvulsive therapy (ECT) shows some efficacy in the treatment of late-life depression, including notable improvements in cognitive function. However, results vary, underscoring the need for more research into this combination treatment.

"Data on ketamine use in ECT are limited, especially in the older adult population. However, available data suggest modest improvement in mood and, intriguingly, in cognition," the authors report.

The findings were presented here at the American Association of Geriatric Psychiatry (AAGP) 2017.

Does Ketamine Augment ECT?

ECT has long been established as a highly effective treatment for major depression, and although its benefits have been shown to extend to older adults, responses can be inconsistent. Adjunctive use of ketamine, a noncompetitive NMDA antagonist, with ECT has been explored in young and old patients alike to improve ECT results.

Ketamine monotherapy has garnered a great deal of interest in recent years, with evidence showing a very rapid improvement of depressive symptoms and suicidal ideation when administered via intravenous infusion.

In the current review, first author Parnika Saxena, MD, of the David Geffen School of Medicine, University of California, Los Angeles (UCLA), and colleagues analyzed data from 18 studies that evaluated ketamine as an adjunct to ECT for severe depression in older adults. They also described a quality improvement study of their own that involved the use of ketamine with ECT.

The review included studies involving the modification of ECT with ketamine. Studies included randomized controlled trials, retrospective studies, case series, and single-patient reports. Illnesses included major depressive disorder, bipolar depression and schizoaffective disorder.

The investigators found that the combination treatment was associated with significant improvement in depression in four of eight studies involving older adults. In one study, a case series of nine elderly patients, 5 of 6 patients who responded to therapy were older than 65 years. The only participant in that study who experienced sustained remission with combination therapy was also older than 65.

The review also examined the effect of the combination therapy on cognition in elderly patents. Data on elderly patients were available in 6 of 8 studies

Of these six studies, not all of the results were favorable. One study showed slower reorientation time, and another showed a worsening of verbal fluency following treatment. However, in the other four studies, the combination treatment was associated with significant improvement in cognitive function.

Improved, More Stable Mood

In a separate quality improvement study that Dr Saxena and colleagues conducted at their own center at UCLA, ECT/ketamine therapy had a greater effect among elderly patients with either unipolar depressive disorder with differing subtypes or bipolar depressive disorder.

That study included 35 patients, of whom 16 were aged 65 years or older. Patients received ECT with ketamine (0.5 mg/kg) as an adjunct to either etomidate, remifentanil, methohexital, or a combination thereof. Among the patients older than 65, the mean age was 74.5.

The ECT involved bilateral or bifrontal lead placement in 13 of the 16 older patients and right unilateral placement in the remaining three.

Of the 16 older patients, nine reported subjective improvement in mood and/or mood stability.

Two of the nine did not continue with maintenance ECT after completion of index courses of treatment. One of the patients dropped out because of anxiety surrounding the procedure, and another because of cognitive worsening.

Patients underwent mood assessment with the Patient Health Questionnaire–9 (PHQ-9). For patients aged 65 and older, the mean PHQ-9 score at baseline was 20.3; it was 10.8 following completion of the last treatment.

The PHQ-9 improvement of 46.8% in those older than 65 was significantly higher than the 25.7% improvement (baseline 18.12, vs 13.47 at completion) for those younger than 65 who received ketamine as an adjunctive therapy.

Impact on Cognition

For the older patients, the mean Montreal Cognitive Assessment (MOCA) score at baseline was 23.4; at completion, it had dropped to 21. By comparision, for those younger than 65, the mean baseline MOCA score was 27; it had dropped to 26.56 at completion.

The discontinuation rate of 12.5% (two patients) among those aged 65 and older was significantly lower than the rate of 36.8% (seven patients) in the younger-than-65 group. This is consistent with some reports of the use of ketamine in older vs younger patients, Dr Saxena told Medscape Medical News.

"A majority of the younger patients dropped out due to inefficacy of treatment," Dr Saxena said.

"Given that our anecdotal experience has been that the elderly patients respond well to adjunctive ketamine, it was not surprising that they had better compliance with this regimen."

Ketamine is linked to possible dissociative effects when administered as monotherapy, but these potential effects of the drug are difficult to distinguish from similar effects of ECT.

"Ketamine can have hypertensive effects and in some cases is reported to cause increased confusion after ECT treatment," Dr Saxena explained.

"However, this finding is confounded by the fact that ECT and other anesthetics themselves can cause some confusion post treatment. Our study did not demonstrate increased dissociative effects from adding ketamine," Dr Saxena noted.

The authors have disclosed no relevant financial relationships.

American Association of Geriatric Psychiatry (AAGP) 2017. Abstract EI 9, presented March 25, 2017.

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