Ketamine Noninferior to ECT for Outpatients With Major Depression

NEW YORK CITY -- Treatment with ketamine was noninferior to electroconvulsive therapy (ECT) for major depressive disorder, two meta-analyses showed, though it was inferior for patients hospitalized with major depressive episodes in one of them.

One meta-analysis that included data from six randomized controlled trials showed no significant difference in overall changes in depression severity between the ketamine and ECT groups immediately after treatment (standard mean difference 0.18, 95% CI -1.65 to 2.01), reported Noor Atiq, MBBS, of King Edward Medical University in Lahore, Pakistan, at the American Psychiatric Association (APA) annual meeting.

There were no statistically significant differences in response rates (risk ratio [RR] 0.94, 95% CI 0.72-1.23) or remission rates (RR 0.91, 95% CI 0.47-1.78) between the two treatment groups.

"Such a treatment can be very beneficial for such patients," Atiq told MedPage Today, noting that ketamine could be effective for people who cannot undergo general anesthesia [and] who have contraindications to the use of ECT.

Atiq, who is an international medical graduate, said she has also observed how people outside the U.S. have negative views of ECT.

"People do consider ECT to be a very barbaric treatment," Atiq said. "It's stigmatized in a way. A lot of patients would not follow-up with you if you advise them [on] ECT, even if they're in a really bad state."

The second meta-analysis, which also included six randomized controlled trials, showed that ketamine was noninferior to ECT for treating major depressive episodes in patients without psychosis (risk difference -0.03, 95% CI -0.22 to 0.16), reported Arthur Petrucci, a medical student at Federal University of Paraíba in João Pessoa, Brazil.

There was no statistically significant difference in treatment response rates between the ketamine and ECT groups for depressive symptoms (risk difference -0.10, 95% CI -0.26 to 0.05).

However, ketamine was inferior to ECT among inpatients (risk difference -0.15, 95% CI -0.27 to -0.03).

Recent studies, such as the ELEKT-D trial, have shown that ketamine worked just as well as the current "gold standard" of ECT for outpatients without psychotic features, but Atiq noted that patients should still be made aware of the side effects of the therapy.

The meta-analysis by Atiq and colleagues showed that ketamine was associated with a lower risk of muscle pain or weakness (RR 0.23, 95% CI 0.14-0.39), but a higher risk of dissociation or depersonalization (RR 5.17, 95% CI 2.17-12.31).

"Ketamine can cause hallucinations, a sense of depersonalization (being outside of your body), increased heart rate [and] blood pressure -- [these are] things that need to be checked before prescribing any medication," Atiq said. "With ECT, there are chances of cognitive impairment. A lot of research has been done on that as well."

"Patient-specific treatment is ideal," she added.

Atiq and colleagues analyzed data from over 600 patients in six randomized trials. Among those trials, four were conducted in inpatient settings, one in an outpatient setting, and one in an unspecified setting.

Petrucci and colleagues analyzed data from 655 patients in six randomized trials. Of those, 51% were inpatients. Treatment duration ranged from 1 to 3 weeks, and follow-up ranged from 2 weeks to 13 months.

While both meta-analyses found that ketamine was noninferior to ECT in certain settings and patient populations, Atiq explained that there is likely a need for more robust evidence in favor of this treatment.

"Further research is definitely needed, [and] definitely more trials are needed," she said.