This study focuses on helping people with Major Depression (a serious mood disorder causing sadness and loss of interest) and Suicidal Ideation (thinking about or planning suicide). Participants will be treated with esketamine, a medication that can be sprayed into the nose to help improve mood quickly. After this, participants will either receive CBT (Cognitive Behavioral Therapy), a type of talk therapy done with a computer, or TAU (Treatment As Usual), which is standard care without the added therapy.

The study will explore how well CBT works with esketamine to prevent depression from returning. People aged 18-65 with major depressive disorder and suicidal thoughts can join, but they need to agree to certain conditions like using reliable contraception. However, people with certain mental health conditions or medical issues, like bipolar disorder or active substance use disorder, cannot participate.

• Participants must agree to join all visits and treatments throughout the study.
• The study aims to enroll 100 people who are willing to be part of either inpatient or outpatient settings.
• This is a research study, and participants will not receive direct compensation.