Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity

Abstract

Background: A large number of studies indicate that subanesthetic doses of ketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route, and it remains unclear for whom this treatment is most suitable. Aims: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine in unipolar and bipolar treatment-resistant depression (TRD) and clinical predictors of response. Methods: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment was carried out. Doses started at 0.5 mg/kg and it could be titrated up to 1 mg/kg, according to response. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups were made through analysis of variance and treatment effects. Results: At baseline, our sample presented with severe treatment resistance in 65.7%, as assessed by the Maudsley Staging Method (MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR = 3.162, p = 0.041) and anxiety disorder comorbidity (OR = 3.149, p = 0.028). Conclusions: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with depression and comorbid anxiety. Therefore, future research could investigate whether esketamine should receive a more prominent place in the treatment algorithm for TRD.

Subcutaneous Ketamine in Depression: A Systematic Review

“…The cost-effectiveness of ketamine was evaluated in previous studies for traumatic injuries (36) and Chiari disease (39). Despite potentially important cost-benefit advantages associated with the use of an SC route for treating depression, the present review showed that, up to now, only the costs of an esketamine ampoule (50 mg/mL, 2 mL) has been presented in the literature, costing BRL R$15.00 (∼US$2.70) for approximately two dosages (26). For comparison, the costs estimated for IN esketamine range from U$5,664 to 8,142 for the first month of treatment, while IV racemic ketamine costs in the United States range from U$500 to 1,000 per session (14).…”

“…Favorable results regarding both efficacy and safety were reported in case reports (21)(22)(23)(24)(25). Data from retrospective studies (20,(26)(27)(28)(29) and two clinical trials (17,18) also confirmed efficacy and a solid tolerability profile associated with SC administration of ketamine for depression. Considering the paucity of data, we will discuss efficacy and tolerability of these results qualitatively, keeping in mind the limited nature of the data at hand.…”

“…Of the selected articles, two were randomized clinical trials (17,18) five were case-reports (21,22) and five were retrospective studies (20,(26)(27)(28)(29) (see Table 2). From the retrospective studies, four of them (26)(27)(28)(29) were from the intervention in the same group of patients and, thus, will be presented together in Tables 2, 3.…”

“…No data were presented regarding costs or cost-effectiveness of the SC route in depression. The only estimated cost was presented by Lucchese et al (26) of one esketamine ampoule (50 mg/mL, 2 mL) at BRL R$15.00 (∼US$2.70) for approximately two dosages.…”

“…Our ability to evaluate the dose-response effect of the SC route measured in the two trials with ketamine, as well as the four retrospective studies (26)(27)(28)(29) and two case-reports (24,25) with esketamine in comparison to IV studies is limited since the latter studies used fixed doses. However, findings from dose-titration studies appear promising with patients remitting following low doses.…”