Repeated Intranasal Esketamine Plus Almond Therapy in Patients With Treatment Resistant Depression

Inclusion Criteria:

* Score on MADRS scale with a score of 18 or greater
* Meet criteria for Treatment-Resistant Major Depressive Disorder, defined as having not responded adequately to at least two separate courses of treatment with different antidepressant at an adequate dose and duration in the current moderate to severe depression episode, as determined by an appropriately trained psychiatrist.
* Women of child bearing potential must use a medically acceptable means of contraception for the duration of the study and for 6 weeks after the last dose of esktamine.
* Negative blood pregnancy test prior to baseline
* If currently receiving medication for depression, antidepressant dose must be stable for the previous 4 weeks prior to baseline.
* Stable dose of all other medication for at least 1 month prior to baseline
* Controlled hypertension and on a stable dose of antihypertension medications for at least 3 months prior to baseline visit

Exclusion Criteria:

* Women who plan to become pregnant, are pregnant or are breastfeeding
* Serious unstable medical illness as determined by the Investigator.
* Participants with uncontrolled hypothyroidism and hyperthyroidism
* Hormonal treatment (e.g., Estrogen) started within the 3 months prior to first dose of study treatment.
* Participants who report treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to the first dose of esketamine.
* Participants with confirmed psychotic disorder or symptoms, bipolar disorder and or clinically significant alcohol or substance misuse confirmed by a psychiatrist in the previous 2 years.
* Previous ketamine abuse as determined by Investigator
* Previous non-response to clinical or research ketamine administration
* Current diagnosis of bulimia nervosa
* Participants who have been diagnosed with ADD/ADHD and who are also currently taking stimulant medication such as methylphenidate or another amphetamine-type medication.
* Participants currently taking St John's Wort, Ginseng or Turmeric
* Participants judged clinically to be actively at serious risk of self-harm or suicidal behaviour by the study team or psychiatrist at Screening.
* Blood pressure \>140/90 at screening