None listed
Conditions
Brief summary
Major depression affects one in 16 young Australians. The first line of pharmacological treatment for severe depressive disorders in young people is selective serotonin reuptake inhibitors (SSRI). However, beneficial clinical effects are rarely observed before 4-8 weeks, whilst negative side effects (e.g., increased activity leading to increased suicide risk) are present. Consequently, a major question is whether there is a treatment strategy that could alleviate depressive symptoms in the initial 4-8 weeks? Recent data showed that a single dose of nitrous oxide (N2O) in adults with severe depression had significant antidepressant effects, and maximum effects were observed 24 hours after administration. However, no studies using N2O in minors have been conducted. The proposed research aims to investigate whether N2O has the same antidepressant effects in minors by using a between-group single-blind design. Participants will be randomly allocated to treatment (N2O) or placebo, and monitored weekly up to 12 weeks after treatment initiation. We expect that an average improvement in mood will be observed for the group allocated to the nitrous oxide condition.
Interventions
This intervention will consist of a single inhaled dose of nitrous oxide.
The study design will be a randomised single-blind placebo controlled trial, and the study will consist of two phases, Phase A and Phase B. During Phase A, participants will receive a dose of either nitrous oxide (N2O), or placebo (blinded to participants). Phase B will last for 12 weeks, and will consist of weekly psychiatric follow ups conducted by Consultant Psychiatrists.
Prior to Phase A, all participants and their
This intervention will consist of a single inhaled dose of nitrous oxide. The study design will be a randomised single-blind placebo controlled trial, and the study will consist of two phases, Phase A and Phase B. During Phase A, participants will receive a dose of either nitrous oxide (N2O), or placebo (blinded to participants). Phase B will last for 12 weeks, and will consist of weekly psychiatric follow ups conducted by Consultant Psychiatrists. Prior to Phase A, all participants and their caregivers will be provided with an information sheet and consent form prior to the commencement of the study. The information sheet that will be provided will outline the rationale of the study, the tasks that the participants will be asked to complete. The procedure of Phase A is as follows: Participants will arrive at Princess Margaret Hospital, and will be assessed by a Consultant Psychiatrist. They will then be randomly allocated to either a group receiving nitrous oxide (50% N2O / 50% O2) or a second group receiving a placebo (50% nitrogen / 50% oxygen). For both groups, the flow rate will be 6L per minute for 60 minutes. Group assignment will be performed using a random number generator. Apart from the inhalational mixture, the sessions for administration of N2O and placebo will be indistinguishable as regards to their setting, setup, and monitoring. Standardized mood assessment will take place at baseline as well as 2 and 24 hours after N2O / placebo administration, and at weekly intervals into fluoxetine administration. Phase B will begin 24 hours after Phase A. All participants that were enrolled will be prescribed with fluoxetine (an intention to start treatment with fluoxetine is an inclusion criteria). Participants will be prescribed and administered fluoxetine in a fixed-dose approach, which will employ a fixed dose of fluoxetine of 20mg per day (after an introduction period of 7 days with 10 mg). The total duration of administration will be the duration of the study period (i.e., 12 weeks), and will be administered via oral tablets. Adherence to fluoxetine will be monitored by empty drug packet return. With regard to fluoxetine treatment, the participant would have been consented for this off-label medicine in minors, and a baseline ECG and thyroid function test would have been completed. Fluoxetine will be continued with weekly monitoring of clinical symptoms and mood.
Sponsors
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, The University of Western Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Participants with a confirmed diagnosis of moderate to severe Major Depressive Disorder (according to ICD-10 or DSM-V) 2. Participants aged between 12 and 17 years 3. Intention to start fluoxetine as treatment in Phase B
Exclusion criteria
1. Active suicidal ideation or plans 2. Currently taking other psychiatric medications at study entry 3. Intellectual disability 4. Active or past diagnosis of an eating disorder 5. Current or recent abuse of alcohol and current or recent abuse of illicit substances or dependence (recent = within the past 12 months). 6.Pregnancy in female participants 7. Chronic medical or neurological disorder 8. History of bipolar disorder, schizophrenia, schizoaffective disorder, obsessive compulsive disorder, or other Axis II diagnosis 9. Presence of acute medical illness that could interfere with study participation, including (but not limited to) significant pulmonary disease. 10. Active psychotic symptoms 11. Previous administration of NMDA receptor antagonists (e.g., N2O or ketamine) during the preceding 3 months. 12. Ongoing or past treatment with electroconvulsive therapy 13. Contraindications against the use of N2O (e.g. pneumothorax) 14. Contraindications against the use of fluoxetine
Outcome results
None listed