elderly patients are significantly impacted by MDD and are less responsive to treatment. ECT is used more often in older patients but has its drawbacks. There is a need for for novel antidepressants. Esketamine, is a FDA approved novel treatment to treatment resistant depression(TRD). Studies of esketamine nasal spray administered with a newly initiated oral antidepressant in TRD aged patients 18-64 years demonstrated rapid onset versus a newly initiated oral antidepressant plus placebo, with maintenance of the treatment effects following long term intermittent dosing. Side effects are dose related, psychotomimetic dissociative, elevation in HR+BP, cognitive impairment, hepatotoxicity and inflammation of bladder endothelium.

to review the current data regarding esketimine treatment in elderly TRD patients.

beside several case reports only 2 RCTs checked efficiency and safety in elderly patients. A pilot RCT of titrated subcutaneous ketamine in older patients with TRD was conducted in 2017. 16 participants> 60 years with TRD who relapsed after remission or did not remit in the RCT were than administered an open label phase. Up to 5 doses of ketamine (0.1 to 0.5 mg\kg) were administered with midazolam as an active control, randomly inserted. 12 ketamine treatments were given in separate sessions at least 1 week apart. Remitters in each phase were followed up for 6 months with MADRS scale. Results provided evidence for the efficacy and safety of ketamine in treating elderly depressed. There was a significant improvement in all ketamine dosages apart from 0.1 mg/kg. 7 participants reached remission. 5/7 had relapse than entered open trial and remitted again. Ochs-Ross, et al 2020 study,138 patients with TRD> 65 years received flexibly dosed esketamine nasal spray and new antidepressant or new antidepressant with placebo. The groups did not achieve statistical significance in MADRS score change from baseline to day 28. Patients with earlier onset of depression and younger patients (65-74) showed greater response to treatment.

Esketamine is safe in elderly TRD patients. There is not enough evidence to conclude if it is efficient. It seems that patients younger than 75 and with earlier onset of depression might benefit from esketamine.