Esketamine-Nasal Spray Safe and Effective for Treatment-Resistant Bipolar Depression

Esketamine-nasal spray (ESK-NS) was found to be effective and tolerable for treatment-resistant bipolar depression (B-TRD) in a real-world setting. These findings were published in Bipolar Disorders.

The REAL-ESK study was an observational, retrospective, multicenter study conducted in Italy. Patients (n=35) with B-TRD who had received early access to ESK-NS through national mental health centers were retrospectively compared for outcomes at 3 months with a matched group of patients with treatment-resistant depression (TRD; n=35) who had also received ESK-NS.

The B-TRD and TRD cohorts comprised patients with mean ages 52.77±10.9 and 52.77±10.9 years, the male:female ratios were 17:18 and 15:20, their depression onset at 33.31±11.65 and 34.35±14.2 years of age, the duration of their depressive episode was 15.94±11.81 and 13.68±11.12 months, and 11 and 4 patients had previously attempted suicide, respectively.

The B-TRD and TRD cohorts were receiving selective serotonin reuptake inhibitors (45.71% vs 45.71%), serotonin-norepinephrine reuptake inhibitors (20% vs 42.8%), and other antidepressants (51.43% vs 54.28%), respectively. In addition, the B-TRD cohort had a higher rate of taking mood stabilizers (100% vs 57.14%) and antipsychotics (68.57% vs 45.7%) compared with the TRD cohort, respectively.

Esketamine was dosed at 84 mg for 28.6% of the B-TRD and 60% for the TRD recipients, 56 mg for 57.1% and 34.3%, and 28 mg for 14.3% and 5.7%, respectively.

At baseline, average Montgomery–Åsberg Depression Rating Scale (MADRS) scores were 37.07 points among the B-TRD group. After 1 month of treatment, MADRS scores decreased to 24.04 points and to 12.78 points after 3 months of treatment. The MADRS scores for the TRD group were comparable at baseline (mean, 34 points) and after 1      (mean, 21.79 points) and 3 (mean, 14.97 points) months of EST-NS treatment, respectively.

The proportion of responders after 1 month of treatment were 25.7% and 25.7% and after 3 months were 68.57% and 57.14% in the B-TRD and TRD groups, respectively. However, 48.57% of the B-TRD group were MADRS remitters in month 3 compared with 28.57% in the TRD group.

For Hamilton Anxiety Rating Scale (HAM-A) scores, similar decreases in scores were observed among the B-TRD and TRD groups from baseline (mean, 29.88 vs 30.9 points) to 3 months of treatment (mean, 11.2 vs 16.2 points), respectively. As with symptoms of depression, more of the B-TRD group remitted in month 3 compared with TRD (35% vs 2.86%; P =.002), respectively.

Fewer of the B-TRD cohort reported any side effect (57.14%) compared with the TRD group (77.14%). Among the B-TRD group, the most common side effects were dissociation (31.4%) and sedation (28.57%). The rate of affective switch or maniacal symptom development was rare (2.86%) in both groups.

The major limitation of this study was the small sample size.

Study authors concluded, “Our findings support the effectiveness and tolerability of ESK-NS in a real-world population of subjects affected by B-TRD. The prolonged effectiveness to 3 months and the possible action on mixed features in patients with bipolar disorder represent intriguing results. Furthermore, the low risk of manic switch in patients with B-TRD, superimposed on the TRD group, confirms the safety of this treatment.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.