Repeated Intranasal Esketamine Plus Almond Therapy in Participants With Treatment Resistant Depressive Disorder - 3 Month Extension Study

Inclusion Criteria:

1. Participants must have completed Study ZYL-730-01 through to Day 28
2. Adults aged 18-64
3. Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent.
4. Women must use a medically acceptable reliable means of contraception and must agree to use adequate birth control for the duration of the study and for 6 weeks after the last dose using methods from the permitted list for contraception.
5. If currently receiving medication for depression their antidepressant dose(s) must be stable for the previous 4 weeks prior to baseline.
6. Must be on a stable dose of all other medication(s) for at least 1-month prior to baseline visit., unless medication is to treat other short term conditions (i.e. influenza, upper respiratory track infections, pain, etc.)
7. Controlled hypertension and must be on a stable dose of antihypertensive medications for at least 3 months prior to the baseline visit.

Exclusion Criteria:

1. Women who plan to become pregnant, are pregnant or are breastfeeding.
2. Serious unstable medical illness, or any significant change in medical status at the baseline visit and during the study, as determined by the Investigator
3. Hormonal treatment (e.g., Estrogen) started within the 3 months prior to first dose of study treatment.
4. Participants who report treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) at the baseline visit and within 2 weeks prior to the first dose of Esketamine .
5. Participants with confirmed psychotic disorder or symptoms, bipolar disorder and or clinically significant alcohol or substance misuse confirmed by a psychiatrist at the baseline visit. Those participants who develop symptoms of these may be withdrawn from the study, as determined by the Investigator
6. Current diagnosis of bulimia nervosa, or development of significant eating disorder symptoms at the baseline visit or during the study as determined by the Investigator
7. Participants who have been diagnosed with ADD/ADHD and who are also currently taking stimulant medication such as methylphenidate or another amphetamine-type medication, or who are diagnosed with this disorder or who start medication for this during the study.
8. Participants currently taking St John's Wort, Ginseng or Turmeric who start any of these during the study
9. Participants judged clinically to be actively at serious risk of self-harm or suicidal behaviour by the study team or psychiatrist at baseline or at any time during the study, as determined by the Investigator.
10. Blood pressure \>140/90 at baseline
11. Participants who are unable to easily travel to the clinic for all of the in-person visits.