Bipolar Disorder
Conditions
Brief summary
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.
Interventions
DRUGNitrous Oxide
DRUGMidazolam
Sponsors
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
English-speaking; age 20-60 years; BD-I or BD-II, current major depressive episode ≥4 weeks duration; MADRS≥22; taking ≥1 mood stabilizing medication/s (i.e. antimanic anticonvulsant, antipsychotic, and/or lithium).
Exclusion criteria
New medications or changes in dosing, or ECT or TMS, in the preceding 2 weeks; MADRS item 10, \> 4; YMRS≥12; acute significant suicidality; psychosis; substance abuse (past 3 months); active major medical conditions (hepatic, renal, respiratory, or cardio/cerebrovascular disease; diabetes; esophageal reflux; sleep apnea); B12 deficiency/disorders; pregnant; MRI contraindications; history of adverse anaesthetic reactions; anaesthesia class \>2; scuba diving in preceding week.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Asberg Depression Scale (MADRS) score | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day | — |
| Weight | Assessed an average of 3 days after baseline | — |
| Beck Depression Inventory (BDI-II) | Assessed on the drug administration day and followed for 7 days post-drug administration | Self-report measure of mood severity |
| Heart Rate | Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day | — |
| Brief Psychiatric Rating Scale | Assessed on the drug administration day and followed for 7 days post-drug administration | — |
| The Clinician Administered Dissociative States Scale (CADSS) | Assessed on the drug administration day and followed for 7 days post-drug administration | — |
| General Information Sheet (Demographics) | Collected at baseline | Demographics |
| Hamilton Anxiety Rating Scale (HAM-A) | Assessed on the drug administration day and followed for 7 days post-drug administration | Interview measure used to assess anxiety severity |
| Young Mania Rating Scale (YMRS) | 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 | Measures symptom severity |
| Patient Rated Inventory of Side Effects | Assessed on the drug administration day and followed for 7 days post-drug administration | Self-report used to assess side effects |
| CANTAB Medication Listing | Assessed an average of 3 days after baseline | Used to collect medications taken the day before and on the day of blood work |
| Structured Clinical Interview for DSM Disorders | Assessed at baseline | Interview measure used to assess DSM disorders |
| Visual Analogue Scale | Assessed on the drug administration day and followed for 7 days post-drug administration | — |
| Height | Assessed an average of 3 days after baseline | — |
| Endothelial Function assessed via RH-PAT using the EndoPAT. | Assessed an average of 3 days after baseline and lasts approximately 30 minutes | Will be assessed via RH-PAT using the EndoPAT. |
| Frontal Perfusion assessed using an MRI scan | Assessed approximately 5 days after baseline and post-drug administration | Will be assessed using an MRI scan. |
| Biomarkers (B12 and nitric oxide (NO)) | Assessed an average of 3 days after baseline | B12 and nitric oxide (NO) will be examined as predictors of response owing to known associations with the mechanism of action of N2O. |
| Hamilton Depression Rating Scale (HDRS) | Assessed on the drug administration day and followed for 7 days post-drug administration | Interview measure used to assess mood severity |
Countries
Canada
Outcome results
None listed