Treating Bipolar Depression with Esketamine: Safety and Effectiveness data from a naturalistic multicentric study on Esketamine in Bipolar versus Unipolar Treatment-Resistant Depression

This open-label study (n=70) compared the effect of esketamine (28-84mg; 8x) in those with bipolar treatment-resistant depression (B-TRD, n=35) and those with unipolar TRD. There was no significant difference between the two groups on depression scores, and both responded to treatment. Those in the B-TRD group had more anxiety-reducing effects. This study is part of the REAL-ESK study.

Abstract

“Background Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD.

Objectives To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch.

Methods Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up.

Results A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch.

Conclusions Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.”

Authors: Giovanni Martinotti, Bernardo Dell’Osso, Giorgio Di Lorenzo, Giuseppe Maina, Alessandro Bertolino, Massimo Clerici, Stefano Barlati, Gianluca Rosso, Marco Di Nicola, Matteo Marcatili, Giacomo d’Andrea, Clara Cavallotto, Stefania Chiappini, Sergio De Filippis, Giuseppe Nicolò, Pasquale De Fazio, Ileana Andriola, Raffaella Zanardi, Domenica Nucifora, Stefania Di Mauro, Roberta Bassetti, Mauro Pettorruso, Roger S. McIntyre, Stefano L. Sensi, Massimo di Giannantonio, Antonio Vita & the REAL-ESK Study Group