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

Prior treatment

• Concomitant major unstable medical illness such as poorly controlled high blood pressure or patients diagnosed with enlarged prostate or reporting any other urinary related issues
• Diagnosis of severe personality disorder as assessed during the initial consultation with a physician at the Temerty Centre prior to study entry
• Any significant neurological disorder (e.g., a space occupying brain lesion, a history of stroke, a cerebral aneurysm, a seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
• Individuals requiring a benzodiazepine with a dose equivalent to lorazepam 2 mg/day or higher; being on any anticonvulsant(e.g. Lamotrigine) and/or opioid medication due to the potential of these medications to limit the efficacy of ketamine
• Individuals with cognitive or physical impairment which may potentially interfere with IN ketamine administration and subject's ability to stay in the same place for a 2-hr monitoring supervision as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
• Any intracranial implant (e.g., aneurysm clips, shunts, cochlear implants) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed given that we will be using TMS-EMG/EEG

Other illness

• Individuals with history of a DSM-IV substance use disorder (i.e. dependence or abuse) within the past month; and lifetime history of ketamine substance use disorder as confirmed by the MINI
• Stage 2 hypertension defined as a systolic pressure of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or higher on three consecutive readings taken 5 minutes apart
• Presence of cardiac decompensation/heart failure
• DSM-IV diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder (current) as confirmed by the MINI
• Individuals unable to communicate in spoken and written English fluently enough to complete the required study assessments due to a language barrier or a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete clinical assessments)
• Any known allergy to the study medication or any component/ingredient of the ketamine preparation

Lab values

• Results of liver function tests (ALT, AST) are three times or greater than the upper limit of normal readings
• Individuals presenting with a medical condition, a medication, or a laboratory abnormality that could cause a major depressive episode or significant cognitive impairment in the opinion of the investigator

Other

• Pregnancy or the intention to become pregnant and breastfeeding during the study as confirmed by self-report. Female participants of reproductive potential must be willing to use a medically acceptable method of birth control which include highly effective (e.g. approved hormonal contraceptives, IUD, tubal ligation) or double barrier (e.g. male condom with diaphragm, male condom with cervical cap) methods of contraception or abstinence if that is the usual and preferred lifestyle of the participant
• Current episode meeting criteria for mania/hypomania or mixed episode as per DSM-IV criteria on the MINI or as determined by the study team
• Those unable to secure escort to accompany them back home after ketamine sessions will also be excluded from this study

• Individual meeting DSM-IV diagnostic criteria for Bipolar Disorder, current depressive episode as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
• Individuals capable to provide consent and able to communicate, read and write in English
• Individuals currently depressed defined as scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
• Individuals currently experiencing suicidal ideation as defined by a score of 9 or higher on the scale for suicide ideation (SSI)