Study protocol.

BackgroundNitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.MethodsIn this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score DiscussionThis pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.Trial registrationClinicalTrials.gov NCT04957368. Registered on July 12, 2021.</div

SPIRIT checklist.

BackgroundNitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.MethodsIn this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score DiscussionThis pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.Trial registrationClinicalTrials.gov NCT04957368. Registered on July 12, 2021.</div

Schedule of enrolment, interventions, and assessments.

Schedule of enrolment, interventions, and assessments.</p

sj-docx-1-cpa-10.1177_07067437231203433 - Supplemental material for Influence of <i>CYP2C19</i>, <i>CYP2D6</i>, and <i>ABCB1</i> Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study

Supplemental material, sj-docx-1-cpa-10.1177_07067437231203433 for Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study by Farhana Islam, Leen Magarbeh, Samar S. M. Elsheikh, Stefan Kloiber, Caroline W. Espinola and Venkat Bhat, Benicio N. Frey, Roumen Milev, Claudio N. Soares, Sagar V. Parikh, Franca Placenza, Stefanie Hassel, Valerie H. Taylor, Francesco Leri, Pierre Blier, Rudolf Uher, Faranak Farzan, Raymond W. Lam, Gustavo Turecki, Jane A. Foster, Susan Rotzinger, Sidney H. Kennedy, Daniel J. Müller in The Canadian Journal of Psychiatry</p