This study is a 7-day randomized, double-blind proof-of-concept pilot study of nitrous oxide vs. midazolam in 40 adults (20-60 years) with bipolar disorder (BD) (type I or II). Ongoing pharmacological and psychosocial treatments may continue, provided that they have not been initiated or significantly modified in the preceding 2 weeks. Participants' current treatment as prescribed by clinical psychiatrists will not be modified or interfered in this study. The study involves 3 visits. During study visit 1, participants will complete screening to ensure study eligibility. This will be done using interview measures. During study visit 2, participants will complete anthropomorphic measurements, measurement of endothelial function, screening blood work, ECGs, and an anaesthesia screener. During study visit 3, participants will receive the treatment (nitrous oxide or midazolam), complete an MRI scan, and complete interview measures and self-reports. There will be anthropomorphic measurements taken as well. The participant will be required to complete phone interviews and self-reports over the subsequent 7 days. There are 4 main predictions: 1. Nitrous oxide will significantly reduce depression symptoms vs. midazolam. 2. Nitrous oxide will significantly increase frontal cortical perfusion vs. midazolam. 3. Lower perfusion in frontal cortical regions at baseline will be associated with greater improvement in depression symptoms following nitrous oxide treatment. 4. Poorer endothelial function will be associated with greater improvement in depression symptoms following nitrous oxide treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
25
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Change in Montgomery-Asberg Depression Scale (MADRS) score
Measures mood symptom severity, used to select patients and assess treatment efficacy. Although other time-points will be examined, 24h was selected as the primary outcome to minimize the impact of acute sedation and psychoactive effects.
Time frame: Assessed at baseline, an average of 3 days later, again at up to 5 days after baseline on the day of drug administration, and participants will be followed for 7 days after the drug administration
Young Mania Rating Scale (YMRS)
Measures symptom severity
Time frame: Assessed at baseline, an average of 3 days later, again at up to 5 days after baseline on the day of drug administration, and participants will be followed for 7 days after the drug administration
Blood Pressure
Time frame: Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day
Weight
Time frame: Assessed an average of 3 days after baseline
Beck Depression Inventory (BDI-II)
Self-report measure of mood severity
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
Heart Rate
Time frame: Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day
Brief Psychiatric Rating Scale
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
The Clinician Administered Dissociative States Scale (CADSS)
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
General Information Sheet (Demographics)
Demographics
Time frame: Collected at baseline
Hamilton Anxiety Rating Scale (HAM-A)
Interview measure used to assess anxiety severity
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
Hamilton Depression Rating Scale (HDRS)
Interview measure used to assess mood severity
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
Patient Rated Inventory of Side Effects
Self-report used to assess side effects
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
CANTAB Medication Listing
Used to collect medications taken the day before and on the day of blood work
Time frame: Assessed an average of 3 days after baseline
Structured Clinical Interview for DSM Disorders
Interview measure used to assess DSM disorders
Time frame: Assessed at baseline
Visual Analogue Scale
Time frame: Assessed on the drug administration day and followed for 7 days post-drug administration
Height
Time frame: Assessed an average of 3 days after baseline
Endothelial Function assessed via RH-PAT using the EndoPAT.
Will be assessed via RH-PAT using the EndoPAT.
Time frame: Assessed an average of 3 days after baseline and lasts approximately 30 minutes
Frontal Perfusion assessed using an MRI scan
Will be assessed using an MRI scan.
Time frame: Assessed approximately 5 days after baseline and post-drug administration
Biomarkers (B12 and nitric oxide (NO))
B12 and nitric oxide (NO) will be examined as predictors of response owing to known associations with the mechanism of action of N2O.
Time frame: Assessed an average of 3 days after baseline
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.