• Ana C Lucchese, Luciana M Sarin, Eduardo J Muniz Magalhães, Lorena C Del Sant, Camila B Puertas, Marco A Tuena, Carolina Nakahira, Victor Ar Fava, Rodrigo Delfino, Juliana Surjan, Matheus S Steiglich, Matheus Barbosa, Guilherme Abdo, Frederico M Cohrs, Aroldo Liberatori, José A Del Porto, Acioly Lt Lacerda, and Sergio B Andreoli.
• Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil.
• J. Psychopharmacol. (Oxford). 2021 Feb 1; 35 (2): 142-149.

BackgroundA 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.AimsThe 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.MethodsA 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.ResultsAt 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).ConclusionsOur 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.

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