Neurological

Esketamine increases the effectiveness of antidepressants and improves sleep in patients with TRD

Esketamine has been shown to be effective as an antidepressant and improve sleep quality in patients with treatment-resistant depression (TRD), according to results of a study published in Neuropsychiatric Disease and Treatment.

Studies TRANSFORM-1 and TRANSFORM-2 were 4-week, double-blind, randomized, active-controlled, multicenter studies of esketamine nasal spray for the treatment of TRD. Patients were randomized to receive esketamine 56 or 84 mg twice weekly (n=343) or placebo (n=222) in combination with an open-label antidepressant. The oral antidepressants were chosen by the doctor from selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.

Both studies evaluated the safety and effectiveness of esketamine over a period of up to 24 weeks. Clinically meaningful sleep improvement was defined as a ≥ 2 point decrease from baseline in point 4 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Continue reading

The patients were between 18 and 64 years old, 65.3% had insomnia and the current depressive episode lasted between 147.2 and 192.3 weeks. Patients with major depression reported more severe sleep disturbances (p<0.001).

Each 1 point higher MADRS score for insomnia at baseline was associated with a 23% greater likelihood of responding to the antidepressant (odds ratio [OR], 1.23; 95% CI, 1.08-1.40; P = 0.001).

Compared to placebo, esketamine was associated with response (OR, 2.05; 95% CI, 1.40-3.02; p<0.001) and remission (OR, 1.81; 95% CI, 1.23-2.66 ; p = 0.003).

Sleep was significantly improved by esketamine by day 8 (difference between groups in MADRS score, -0.4; standard error [SE], 0.12; P=0.001), continued to day 28 (difference between groups in MADRS score, -0.3; SE, 0.15; P=0.020). More esketamine recipients achieved a clinically meaningful improvement in sleep at day 8 (26.1% vs. 15.7%; p=0.004) and 28 (49.0% vs. 41.4%; p=0.038).

There was an association between sleep improvement and antidepressant efficacy, with the more sleep improvement during the first week, the greater the likelihood of antidepressant response by day 28 (OR, 1.26; 95% CI, 1.12– 1.42 per 1-point MADRS improvement; p<0.001). A similar relationship was observed for remission (OR, 1.28; 95% CI, 1.14-1.43 per MADRS 1-point improvement; p<0.001).

Adverse events occurring in > 10% of esketamine recipients included dissociation, dizziness, dysgeusia, headache, hypoesthesia, oral hypoesthesia, nausea, paraesthesia, somnolence, and dizziness.

This study was limited by not using objective sleep assessment tools such as actigraphy or polysomnography.

The study authors concluded that esketamine supports antidepressant efficacy and improves sleep quality in patients with TRD regardless of sleep disorder status.

Disclosure: Several authors declared their affiliation with the industry. For a full list of disclosures, see the original article.

relation

S. Borentain, D. Williamson, I. Turkoz et al. Effect of sleep disorders on the efficacy of esketamine in treatment-resistant depression: results from randomized controlled trials. Neuropsychiatrist Dis Treat. Published online November 30, 2021. doi:10.2147/NDT.S339090

This article originally appeared on Psychiatry Advisor

Related Articles