Early ECT Efficacious, Cost-effective for Resistant Depression

Batya Swift Yasgur, MA, LSW

May 15, 2018

Electroconvulsive therapy (ECT) is both efficacious and cost-effective for patients with treatment-resistant depression (TRD) and should be considered as a third-line strategy for those for whom two previous treatment trials have failed, new research suggests.

Utilizing data from an array of studies, investigators integrated findings regarding the effects of ECT on efficacy, costs, and quality of life (QOL) in comparison with pharmacotherapy or psychotherapy through a decision analytic model.

The investigators projected that over 4 years, ECT would reduce the amount of time that a patient experienced uncontrolled depression from roughly half of the patient's life-years to roughly one third of the patient's life-years. The model predicted that greater improvements would be experienced if ECT were introduced earlier.

"The main finding for clinicians is that ECT is a cost-effective treatment option for people with TRD — that is, even though ECT is very expensive, its benefits are great enough to make it a good value," lead author Eric L. Ross, MD, a recent graduate of the the University of Michigan Medical School, told Medscape Medical News.

"In addition, we were surprised to find that offering ECT relatively early in the course of depression treatment — after a patient has failed to respond to two prior treatments — is cost-effective, which would represent a fairly substantial change from current practice that often views ECT as a 'last resort' treatment to be used only after 5 to 10 medications and psychotherapies have failed," said Ross, who conducted the study with coinvestigators Kara Zivin, PhD, associate professor of psychiatry, health management, and policy, and Daniel Maixner, MD, associate professor of psychiatry, both at the University of Michigan, Ann Arbor.

The study was published online May 9 in JAMA Psychiatry.

Novel Analytic Model

ECT is a "highly effective treatment" for depression. Research suggests that it may be more effective than pharmacotherapy and psychotherapy in helping patients achieve rapid remission, the authors write.

Despite its benefits, its use "remains low," for reasons that include stigma, adverse effects, and lack of access.

In the United States, ECT is most frequently used for depression in patients for depression that has failed to respond to pharmacotherapy or psychotherapy. Some patients spend months to years with uncontrolled depression before ECT is offered.

The high cost of ECT may limit its use. The initial course requires 5 to 15 treatments, at an estimated cost of $300 to $1000 per treatment. Ten to 20 treatments per year are required, the investigators state.

No prior study has reported on the cost-effectiveness of ECT in the United States or has evaluated at what point in the course of treatment ECT should be offered, the authors point out.

"We wanted to determine if ECT provided enough health benefit for people with depression to warrant its very high cost," Ross explained.

"Additionally, we wanted to clarify criteria for whom ECT is warranted in people with depression, that is, how many treatment options must a patient exhaust without benefit before ECT becomes cost-effective for that patient," he said.

To investigate these questions, the researchers developed a decision analytic model to assess the cost-effectiveness of several strategies for offering ECT to patients with major depressive disorder (MDD).

The strategies were characterized by the number of prior treatment lines (defined as "a unique combination of antidepressant medications and/or psychotherapy") that a patient was required to have received before ECT was initiated.

The researchers simulated seven strategies: one without ECT, and six with zero to five lines of therapy prior to administration of ECT.

The researchers "preferentially used" data sources that that did not target suicidality or psychosis. However, because of the "substantial overlap" between psychosis, suicidality, and TRD, some studies included all three.

The researchers simulated the clinical and economic effects of the seven strategies over a 4-year period.

They calculated overall quality-adjusted life-years (QALYs), a measure that combines longevity with health-related QOL, and costs from a healthcare sector perspective.

The simulated cohort of patients with MDD entered the model at initiation of first-line treatment and then progressed through as many as nine lines of treatment.

The researchers used the STAR*D data to simulate a population with a mean age of 40.7 years (SD, 13.2 years), of whom 62.2% were women.

Use of several other analyses and databases showed an increase in annual costs with every failed treatment. Annual costs ranged from $7833 to $16,816 per year for 0 to 8 prior trials.

Additional meta-analyses and randomized controlled trials were used to assess the utility, efficacy, and cost of ECT in comparison with approaches to treatment based on the use of antidepressants and psychotherapy.

Sensitivity and uncertainty analyses were applied to the findings of their model. To estimate overall uncertainty, the process was repeated 10,000 times.

"Similar approaches — although with different models — have been used in the past to address cost-effectiveness questions in psychiatry and in medicine in general, but we developed this decision analytic model specifically for this study," Ross recounted.

Minimize Barriers

In the base case, the researchers found that ECT was projected to reduce the amount of time a patient with depression spends without a response to treatment from 50.2% of the patient's life-years to 37.1% to 32.9% over a 4-year period. Greater reductions were projected when ECT was offered earlier.

These reductions translated into mean quality-adjusted survival gains of 0.12 to 0.15 QALYs, at incremental costs of $7300 to $12,000.

Although the mean ECT-related cost increased from $9100 to $17,100 when ECT was offered earlier, the mean cost of other forms of healthcare declined from $42,500 (without ECT) to $37,400 (with first-line ECT).

When a willingness-to-pay threshold of $100,000 per QALY was applied, third-line ECT was projected to be cost-effective, with an incremental cost-effectiveness (ICER) of $54,000 per QALY.

By contrast, second- and third-line ECT were not cost-effective (ICER of $564,000 and $815,000 per QALY, respectively). Fourth-, fifth-, and sixth-line ECT each offered even fewer QALYs at a worse ICER than did other strategies.

When univariate sensitivity analyses were applied, third-line ECT remained cost-effective across all individual parameter variations.

The findings projected a 74% to 78% likelihood that ECT would be cost-effective in the United States, given commonly accepted cost-effectiveness thresholds (ICER ≤$100,000 per QALY) and a 56% to 58% likelihood that third-line ECT is the optimal strategy.

The findings have important implications for practicing clinicians, who should "consider offering ECT to patients with MDD who have failed to respond to 2 trials of pharmacotherapy and/or psychotherapy," the authors write.

The findings also have important implications for healthcare policy, Ross said.

"Our work suggests that there may be a large number of people with TRD who could benefit from ECT but have never been offered it," he noted.

Additionally, "because ECT can improve the lives of people with depression, and it does so at a good value, it is critical that insurers minimize barriers to receiving this treatment," he said.

Reverse the Trend

Commenting on the study for Medscape Medical News, Max Fink, MD, professor emeritus of psychiatry and neurology, Stony Brook School of Medicine, New York, who was not involved with the study, called its conclusion "reasonable, based on the statistics from all the previous studies analyzed."

The authors "were right to encourage consideration of ECT earlier," he said.

However, he noted, "therapy-resistant depression is an ill-defined entity" and the "problem with that lack of precise definition is that this analysis does not distinguish between melancholic and nonmelancholic depression."

Melancholia is a "syndrome of acute onset, disturbed mood, high incidence of suicidal thought and risk, changes in blood pressure, heart rate, and respiration, neuroendocrine changes, and often psychosis," he explained.

"Most TRD cases are varied, which is why the starting point should not be TRD but the difference between melancholic and nonmelancholic depression, since melancholia responds only to imipramine or ECT rather than to other antidepressants, even after multiple trials," he said.

In that population, ECT should therefore be a first-line approach, he emphasized.

Ross added, "ECT availability has been declining for many years, and if we want to be able to offer ECT to everyone who could benefit from it, we'll need a concerted effort to reverse this trend."

This study was supported by the US Department of Veterans Affairs Health Services Research and Development Services. The authors and Dr Fink have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online May 9, 2018. Abstract

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