In the Journals

Ketamine effective for treatment-resistant depression

Twice-weekly and thrice-weekly IV administration of ketamine maintained similar antidepressant efficacy over 15 days among adults with treatment-resistant depression, according to recent findings.

“Ketamine is a noncompetitive, N-methyl-D-aspartate glutamate receptor antagonist that has been approved for use as an anesthetic. Recent studies with ketamine have demonstrated a rapid onset (2 to 24 hours postinfusion) of antidepressant effect. The effect is relatively short-lived, however, and how to sustain ketamine’s efficacy for a longer duration through an optimal long-term dosing regimen has not yet been determined,” Jaskaran B. Singh, MD, of Janssen Research and Development, Titusville, N.J., and colleagues wrote.

To assess efficacy of IV ketamine for sustaining initial antidepressant effects in individuals with treatment-resistant depression, researchers conducted a multicenter, randomized, double-blind study among 68 adults aged 18 to 64 years. Study participants received either IV ketamine (0.5 mg/kg of body weight) or IV placebo administered over 40 minutes two or three times weekly for up to 4 weeks. Participants who discontinued treatment after at least 2 weeks for lack of efficacy were eligible for an optional 2-week open-label phase to receive ketamine with the same frequency as the double-blind phase.

Among participants who received twice-weekly dosing, mean change in Montgomery-Asberg Depression Rating Scale (MADRS) scores at day 15 were –18.4 in the ketamine group and –5.7 in the placebo group.

Among participants who received thrice-weekly dosing, mean change in MADRS scores were –17.7 in the ketamine group and –3.1 in the placebo group.

Researchers found similar associations for ketamine during the open-label phase, with mean changes in MADRS scores of –12.2 at day 4 among those who received twice-weekly dosing and –14 at day 5 among those who received thrice-weekly dosing.

Headache, anxiety, dissociation, nausea and dizziness were the most common adverse events, occurring in at least 20% of treatment groups.

Dissociative symptoms occurred transiently and attenuated with repeated dosing, according to researchers.

“Ketamine, administered intravenously at 0.5 mg/kg of body weight either two or three times weekly, appeared comparably effective in both achieving rapid onset and maintaining antidepressant efficacy in patients with treatment-resistant depression across the 15-day period of assessment for the primary efficacy endpoint. The improvement was similar in the two frequency groups,” Singh and colleagues wrote. “As less frequent treatment administration is usually preferred in order to reduce the patient and clinic burden and costs, this result, taken together with other data acquired during the double-blind and open-label phases, suggests that the twice-weekly treatment regimen administered for 4 to 6 weeks can induce and maintain (through day 15) a robust antidepressant effect in the treatment-resistant depression population.” – by Amanda Oldt

Disclosure: Singh reports employment at Janssen Research and Development and owning stock in the company. Please see the full study for a list of all authors’ relevant financial disclosures.

Twice-weekly and thrice-weekly IV administration of ketamine maintained similar antidepressant efficacy over 15 days among adults with treatment-resistant depression, according to recent findings.

“Ketamine is a noncompetitive, N-methyl-D-aspartate glutamate receptor antagonist that has been approved for use as an anesthetic. Recent studies with ketamine have demonstrated a rapid onset (2 to 24 hours postinfusion) of antidepressant effect. The effect is relatively short-lived, however, and how to sustain ketamine’s efficacy for a longer duration through an optimal long-term dosing regimen has not yet been determined,” Jaskaran B. Singh, MD, of Janssen Research and Development, Titusville, N.J., and colleagues wrote.

To assess efficacy of IV ketamine for sustaining initial antidepressant effects in individuals with treatment-resistant depression, researchers conducted a multicenter, randomized, double-blind study among 68 adults aged 18 to 64 years. Study participants received either IV ketamine (0.5 mg/kg of body weight) or IV placebo administered over 40 minutes two or three times weekly for up to 4 weeks. Participants who discontinued treatment after at least 2 weeks for lack of efficacy were eligible for an optional 2-week open-label phase to receive ketamine with the same frequency as the double-blind phase.

Among participants who received twice-weekly dosing, mean change in Montgomery-Asberg Depression Rating Scale (MADRS) scores at day 15 were –18.4 in the ketamine group and –5.7 in the placebo group.

Among participants who received thrice-weekly dosing, mean change in MADRS scores were –17.7 in the ketamine group and –3.1 in the placebo group.

Researchers found similar associations for ketamine during the open-label phase, with mean changes in MADRS scores of –12.2 at day 4 among those who received twice-weekly dosing and –14 at day 5 among those who received thrice-weekly dosing.

Headache, anxiety, dissociation, nausea and dizziness were the most common adverse events, occurring in at least 20% of treatment groups.

Dissociative symptoms occurred transiently and attenuated with repeated dosing, according to researchers.

“Ketamine, administered intravenously at 0.5 mg/kg of body weight either two or three times weekly, appeared comparably effective in both achieving rapid onset and maintaining antidepressant efficacy in patients with treatment-resistant depression across the 15-day period of assessment for the primary efficacy endpoint. The improvement was similar in the two frequency groups,” Singh and colleagues wrote. “As less frequent treatment administration is usually preferred in order to reduce the patient and clinic burden and costs, this result, taken together with other data acquired during the double-blind and open-label phases, suggests that the twice-weekly treatment regimen administered for 4 to 6 weeks can induce and maintain (through day 15) a robust antidepressant effect in the treatment-resistant depression population.” – by Amanda Oldt

Disclosure: Singh reports employment at Janssen Research and Development and owning stock in the company. Please see the full study for a list of all authors’ relevant financial disclosures.