Summary

• Symptoms of psychosis were assessed as part of the safety evaluation of SPRAVATO (esketamine) nasal spray in phase 2/3 clinical trials in patients with treatment-resistant depression (TRD).^1-6
  • The four-item positive symptom subscale of the Brief Psychiatric Rating Scale (BPRS+; score range, 0-24) was used to assess for potential treatment-emergent symptoms, including suspiciousness, hallucinations, unusual thought content, and conceptual disorganization.^2,7
  • Across all studies,^1-6 mean BPRS+ total scores increased to maximum values of less than 1 (very mild symptoms) 40 minutes postdose from baseline and generally returned to predose values 1.5 hours postdose.⁷
  • In the short-term studies,^1-3 the mean BPRS+ score remained below 1.2 at all postdose timepoints.⁷
  • No adverse events (AEs) of psychosis were reported in any of these studies.⁷
• AEs of psychosis were also evaluated in phase 2/3 clinical trials in patients with major depressive disorder (MDD) and active suicidal ideation with intent.^8,9
  • A 22-year-old male patient in the SPRAVATO plus standard of care (SOC; the SOC antidepressant was venlafaxine) arm received his last dose of nasal spray study medication on day 8 and had a report of mild psychotic symptoms on day 10 and a reported serious AE of acute psychosis (paranoid persecutory ideation) on day 12. On day 13, he had nihilistic delusions and was reported to be dissociated and agitated. With treatment, the acute psychosis resolved on day 62, but his symptoms of psychosis continued into the follow-up period of the study, during which time he received no SPRAVATO. The investigator did not consider the events to be related to SPRAVATO. The patient’s diagnosis was later changed to MDD with psychotic features.⁸
  • Two patients treated with SPRAVATO+SOC in different phase 2 trials for this indication (one in adults and the other in an adolescent patient population) had psychotic symptoms in the double-blind phases (1 was of moderate severity while the other was a serious AE).⁹
    • The serious AE occurred in a 17-year-old in a phase 2 pediatric study. She had symptoms of suspiciousness and paranoia 3 days after her last dose of medication and was hospitalized and treated with aripiprazole. The psychotic episode ended 14 days later. The investigator considered the episode probably related to SPRAVATO.

LITerature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug Files (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 14 May 2024.