This study will explore the effects of esketamine (Spravato®), an FDA-approved nasal spray, on adults diagnosed with treatment-resistant depression (TRD). All participants will receive esketamine as prescribed by a healthcare professional in a clinical setting.
The purpose of this research is to understand whether adding therapeutic support in the form of preparation and integration sessions - before and after the esketamine doses - can enhance the treatment experience and lead to longer-lasting improvements in mood and functioning.
Participants will be randomly assigned to one of two groups:
Esketamine with therapeutic support sessions (integration group) Esketamine without additional support (standard care group) Both groups will receive standard monitoring and psychiatric evaluation during the study. The support sessions offered in the integration group are designed to help participants prepare for their treatment sessions and make sense of their experiences afterward, using a structured, evidence-based approach.
The study will last approximately 8 weeks per participant, with follow-up assessments. The goal is to learn whether integration therapy can improve treatment outcomes, safety, and satisfaction for individuals with depression that hasn't responded to other treatments.
Age: Adults aged 21 to 65 years.
Diagnosis: Current Major Depressive Disorder (MDD) as confirmed by Structured Clinical Interview for DSM5 (SCID-5).
Treatment Resistance: Failure to achieve remission with at least two antidepressants of adequate dose and duration (TRD criteria) as confirmed by SCID-5.
Symptom Severity: Baseline Montgomery-Åsberg Depression Rating Scale (MADRS) ≥30.
Acute Suicide Risk: Immediate need for inpatient psychiatric hospitalization due to suicidal ideation with plan or intent as identified through the C-SSRS.
Psychotic or Bipolar Disorders: Current diagnosis of bipolar I disorder (manic phase), schizophrenia, schizoaffective disorder, or other primary psychotic disorders if stated by participants as a past diagnosis or identified during the SCID-5.
Substance Use Disorder: Active moderate to severe substance use disorder (except nicotine) in the past 6 months as self-identified by participant or during the SCID-5.
Cognitive/Developmental Impairments: Intellectual disability, dementia, or other cognitive/developmental disorders that impair ability to engage meaningfully in structured psychotherapeutic sessions such as preparation or integration, per clinician judgment.