(#24) Long-Term Safety and Efficacy of Esketamine Nasal Spray as Monotherapy: A Post Hoc Analysis of the SUSTAIN-3 Study

Abstract: Introduction: Esketamine nasal spray (ESK) is approved for treatment of adults with treatment-resistant depression as monotherapy or with an oral antidepressant (OAD). SUSTAIN-3 (NCT02782104) was a long-term safety and efficacy study assessing ESK in conjunction with an OAD; a subgroup received ESK without concurrent OAD (i.e., as monotherapy) at the investigatorsí discretion. Here we investigate the long-term safety and efficacy of ESK monotherapy in these patients. Method: Patients who received ESK monotherapy consecutively for >365 days at any point during the study were included: they either never received concomitant OAD or stopped OAD but continued ESK. Remission was defined as Montgomery-≈sberg Depression Rating Scale (MADRS) total score ?12 or Patient Health Questionnaire-9 (PHQ-9) total score < 5. Treatment-emergent adverse events (TEAEs) were monitored throughout. Results: Of 1148 enrolled patients in SUSTAIN-3, 33 received ESK monotherapy for >365 consecutive days; mean (SD) and median duration of continuous monotherapy was 926 (434) and 875 days, respectively. Overall, mean (SD) and maximum ESK exposure was 1241 (550) and 2149 days, respectively. At optimization/maintenance phase baseline, mean (SD) MADRS and PHQ-9 total scores were 11.2 (9.51) and 6.0 (4.82), respectively. By study end, 57.6% and 42.4% of patients receiving monotherapy were in remission based on MADRS and PHQ-9 total scores, respectively, versus 49.6% and 33.9% in the overall population. Commonly reported TEAEs included dizziness, headache, nausea, and upper respiratory tract infection. Conclusion: Patients who received ESK monotherapy consecutively for >365 days experienced similar antidepressant effect as the overall population, with no new safety signals identified.Short Description: Esketamine nasal spray (ESK) has recently been approved as a monotherapy for adults with treatment-resistant depression (TRD), extending the previous indication as an adjunct to oral antidepressants (OADs). This analysis of SUSTAIN-3 (NCT02782104) investigated the long-term efficacy of ESK as monotherapy in adults with TRD. Patients who received ESK as monotherapy consecutively for >365 days experienced similar antidepressant effect as the overall population, with no new safety signals identified.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC, a Johnson & Johnson company