The purpose of this study is to evaluate the effect of esketamine compared to placebo on driving performance as assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test in healthy participants.

This is a Phase 1, randomized (study medication assigned to participants by chance), double-blind (neither Investigator nor participant knows which treatment the participant receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), single-center, single-dose and 3-way crossover (the same medications provided to all participants but in different sequence) study of esketamine in healthy participants. Participants will be randomly assigned to 1 of 6 treatment sequences. The study will consist of 3 parts: Screening Phase (between 21 days and 1 day prior to the first dose administration), a 3-way crossover double-blind, single dose treatment Phase (45 days) and follow-up Phase (7 to 10 days after last dose administration). The maximum study duration for each participant will not exceed 7 weeks. Participants will receive either Treatment A (esketamine 84 milligram (mg) intranasal and 1 placebo capsule), Treatment B (placebo intranasal and 1 mirtazapine 30 mg capsule) or Treatment C (placebo intranasal and placebo capsule) in each treatment period. Driving performance will be assessed primarily by the mean difference of SDLP from an on road driving test. Participants' safety will be monitored throughout the study.

Inclusion Criteria:

• Body mass index (BMI) (weight [kg]/height^2[m^2]) between 18 and 30 kg/m^2 (inclusive), and body weight not less than 45 kg
• Blood pressure (after the participants is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic at Screening and pre-dose on Day 1 of Period 1
• A woman of childbearing potential must have a negative urine pregnancy test at Screening and pre-dose on Day 1 of Period 1
• A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at Screening and pre-dose on Day 1 of Period 1, including: sinus rhythm, heart rate between 45 and 90 beats per minute (bpm), QTc interval less than or equal to 450 milliseconds (ms), QRS interval of less than 120 ms, PR interval less than 200 ms and morphology consistent with healthy cardiac conduction and function 1st degree AV block is exclusionary
• Participant has a valid driving license for more than 3 years, has driven at least 5000 kilometer (km) in the past year and is driving a car regularly

Exclusion Criteria:

• Participant has clinically significant liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic (including cataplexy and cognitive impairment), hematologic, rheumatologic, psychiatric, or metabolic disturbances. A significant primary sleep disorder is exclusionary
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening, as deemed appropriate by the Investigator
• Clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram (ECG) at Screening or on Day 1 of Period 1, as deemed appropriate by the Investigator
• Anatomical or medical conditions that may impede delivery or absorption of study medication (for example, undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; or signs and symptoms of rhinitis predose on Day 1 of Period 1)
• Has an abnormal or deviated nasal septum with any one or more of the following symptoms: blockage of one or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip