Neural Correlates of Ketamine's Anti-suicidal Effects in Bipolar Depression

Inclusion Criteria:

1. Individual meeting DSM-IV diagnostic criteria for Bipolar Disorder, currentdepressive episode as confirmed by the Mini-International Neuropsychiatric Interview (MINI)

2. Individuals capable to provide consent and able to communicate, read and write inEnglish

3. Individuals currently depressed defined as scoring 14 and above on the HamiltonRating Scale for Depression-24 Items (HRSD-24)

4. Individuals currently experiencing suicidal ideation as defined by a score of 9 orhigher on the scale for suicide ideation (SSI)

Exclusion Criteria:

1. Individuals with history of a DSM-IV substance use disorder (i.e. dependence orabuse) within the past month; and lifetime history of ketamine substance usedisorder as confirmed by the MINI

2. Concomitant major unstable medical illness such as poorly controlled high bloodpressure or patients diagnosed with enlarged prostate or reporting any other urinaryrelated issues

3. Stage 2 hypertension defined as a systolic pressure of 140 mm Hg or higher or adiastolic pressure of 90 mm Hg or higher on three consecutive readings taken 5minutes apart

4. Results of liver function tests (ALT, AST) are three times or greater than the upperlimit of normal readings

5. Pregnancy or the intention to become pregnant and breastfeeding during the study asconfirmed by self-report. Female participants of reproductive potential must bewilling to use a medically acceptable method of birth control which include highlyeffective (e.g. approved hormonal contraceptives, IUD, tubal ligation) or doublebarrier (e.g. male condom with diaphragm, male condom with cervical cap) methods ofcontraception or abstinence if that is the usual and preferred lifestyle of theparticipant

6. Presence of cardiac decompensation/heart failure

7. DSM-IV diagnosis of any primary psychotic disorder, bipolar disorder,obsessive-compulsive disorder, or post-traumatic stress disorder (current) asconfirmed by the MINI

8. Current episode meeting criteria for mania/hypomania or mixed episode as per DSM-IVcriteria on the MINI or as determined by the study team

9. Diagnosis of severe personality disorder as assessed during the initial consultationwith a physician at the Temerty Centre prior to study entry

10. Any significant neurological disorder (e.g., a space occupying brain lesion, ahistory of stroke, a cerebral aneurysm, a seizure disorder, Parkinson's disease,Huntington's chorea, multiple sclerosis) as assessed through medical history reviewduring the initial consultation with a physician at the Temerty Centre prior tostudy entry

11. Individuals presenting with a medical condition, a medication, or a laboratoryabnormality that could cause a major depressive episode or significant cognitiveimpairment in the opinion of the investigator

12. Individuals requiring a benzodiazepine with a dose equivalent to lorazepam 2 mg/dayor higher; being on any anticonvulsant(e.g. Lamotrigine) and/or opioid medicationdue to the potential of these medications to limit the efficacy of ketamine

13. Individuals unable to communicate in spoken and written English fluently enough tocomplete the required study assessments due to a language barrier or anon-correctable clinically significant sensory impairment (i.e., cannot hear or seewell enough to complete clinical assessments)

14. Individuals with cognitive or physical impairment which may potentially interferewith IN ketamine administration and subject's ability to stay in the same place fora 2-hr monitoring supervision as assessed through medical history review during theinitial consultation with a physician at the Temerty Centre prior to study entry

15. Any intracranial implant (e.g., aneurysm clips, shunts, cochlear implants) or anyother metal object within or near the head, excluding the mouth, that cannot besafely removed given that we will be using TMS-EMG/EEG

16. Those unable to secure escort to accompany them back home after ketamine sessionswill also be excluded from this study

17. Any known allergy to the study medication or any component/ingredient of theketamine preparation