Esketamine Effective and Costly Treating Treatment-Resistant Depression

Eric L. Ross, MD

While all signs point to esketamine as an effective medication for those suffering from treatment-resistant depression, the cost might be too high to really make a dent in this patient population.

A team, led by Eric L. Ross, MD, McLean Hospital, estimated the cost-effectiveness of esketamine to treat patients with treatment-resistant depression.

Esketamine is a novel intranasally dosed antidepressant that has recently emerged as an option for this difficult to treat patient population after some studies show the medication being effective in a population where several other medications have not worked.

The investigators produced a decision-analytic model parameterized with efficacy data from phase 3 randomized trials of esketamine to simulate the treatment effect of the medication in comparison with oral antidepressants over a five-year horizon, from both societal and health care sector perspectives.

The investigators sought outcomes including remission and response of depression, quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratios for esketamine.

They also calculated value-based prices, defined as the per-dose price where esketamine would become cost-effective given cost-effectiveness thresholds of $50,000/QALY, $100,000/QALY, and $150,000/QALY.

The team also assessed the uncertainty in these outcomes with probabilistic sensitivity analyses.

Some key model parameters included the efficacy of esketamine in comparison to oral antidepressants (RR of remission, 1.39; RR of response, 1.32) and the monthly cost of esketamine ($5,572 for month 1; $1,669-$2,244 thereafter).

The investigators found over 5 years the projected time in remission increased from 25.3-31,1% of life-years, resulting in a gain of 0.07 QALYs. Esketamine increased societal costs by $16,617 and health care sector costs by $16,995. Base case incremental cost-effectiveness ratios were $237,111/QALY for societal costs and $242,496/QALY for health care sector costs.

For the cost-effectiveness threshold of $150,000/QALY, the investigators found the treatment’s value-based price was approximately $140/dose compared to a current price of $240/dose.

Ultimately, it is unlikely that esketamine ends up as a cost-effective option to treat patients with treatment-resistant depression in the US unless prices for esketamine decrease by more than 40%.

"Esketamine is too expensive, but it does work, the question now is 'How do we get the price down?'" Ross said in a statement. “At the end of the day, it's not about saving money," he said. "The goal is to make sure we're getting the most clinical benefit we can for the money we spend."

Last year, investigators led by Vanina Popova, MD, medical director of the Janssen Pharmaceutical Companies at Johnson & Johnson, found that the combination of a flexibly dosed esketamine nasal spray, coupled with a newly initiated antidepressant (duloxetine, escitalopram, sertraline or extended-release venlafaxine) was more effective at treating TRD than a placebo spray taken with the newly initiated antidepressant.

In the study, adults with a history of not responding to at least 2 antidepressants during their current episode, with 1 antidepressant assessed prospectively were randomly assigned to either esketamine with an antidepressant or an antidepressant with a placebo nasal spray.

The study, “Cost-Effectiveness of Esketamine Nasal Spray for Patients With Treatment-Resistant Depression in the United States,” was published online in Psychiatric Services.