None listed
Conditions
Brief summary
The proposed study aims to evaluate the relationships between changes in sleep-wake and circadian parameters and changes in depressive symptoms following adjunctive brexpiprazole treatment in young adults with Major Depressive Disorder and sleep-wake disturbance, who have failed to respond to at least 1 antidepressant treatment for the current episode. More specifically, this study wants to investigate whether a reduction in depressive symptoms following adjunctive brexpiprazole treatment is associated with sleep-wake and circadian rhythm (i.e. body clock) changes. The study will be conducted at Brain and Mind Centre, University of Sydney, and Woolcock Centre for Medical Research. Investigators expect to enroll 50 subjects in the trial.
Interventions
This study is designed as a 16-week (8 weeks active treatment, 8 weeks follow-up), open-label, phase IV clinical trial. It comprises only one treatment arm, with all participants receiving 8 weeks of adjunctive pharmacotherapy with brexpiprazole.
Experimental Study Arm:
Brexpiprazole for 8 weeks (1mg once daily in week 1, titrated to 2mg once daily in weeks 2 to 8)
Intervention: Drug: Brexpiprazole
Intervention in detail:
After baseline clinical, self-report, sleep-wake, and circadian assessm
This study is designed as a 16-week (8 weeks active treatment, 8 weeks follow-up), open-label, phase IV clinical trial. It comprises only one treatment arm, with all participants receiving 8 weeks of adjunctive pharmacotherapy with brexpiprazole. Experimental Study Arm: Brexpiprazole for 8 weeks (1mg once daily in week 1, titrated to 2mg once daily in weeks 2 to 8) Intervention: Drug: Brexpiprazole Intervention in detail: After baseline clinical, self-report, sleep-wake, and circadian assessments (including blood tests, clinical ratings, self-report questionnaires, ambulatory sleep-wake monitoring, and in lab-circadian circadian assessments) all participants will attend a 1-hour psychoeducational session (baseline visit). Subsequently, participants will receive 8 weeks of open-label treatment with brexpiprazole as adjunctive treatment to TAU*. Patients will receive 2mg/day, once daily as tablets, for oral use. The brexpiprazole dosage will be steadily increased from 1mg/day during week 1, to 2mg/day during weeks 2-8 (up-titration). Participants will be contacted by telephone on a weekly basis to monitor side-effects and adherence. After 4 weeks, clinical ratings and self-report questionnaires will be done to assess changes in clinical and functional measures. Ambulatory sleep-wake monitoring will be conducted continuously for the duration of treatment. After 8 weeks of treatment, blood tests, circadian assessments, clinical ratings and self-report questionnaires will be repeated. Follow-up visits will be conducted 4 weeks and 8 weeks after trial completion (including sleep-wake, clinical, and self-report assessments) *TAU (Treatment As Usual) is a current antidepressant treatment with either SSRI or SNRI.
Sponsors
University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
- Aged 18-30 - Major Depressive Disorder diagnosis according to DSM-5 criteria using the Structured Clinical Interview for DSM-5 (SCID) - Current Major Depressive Episode of moderate severity as indexed by QIDS-CR score greater than or equal to 11 at two assessments 2 weeks apart - Failure to respond to at least one adequate trial (i.e., at least 4 weeks) of a pharmacological therapy for the current episode - Current antidepressant treatment must include an SSRI or SNRI (citalopram, fluoxetine, paroxetine, sertraline, escitalopram, venlafaxine, desvenlafaxine, duloxetine) for at least 6 weeks, at a stable dose for 2 weeks prior to study initiation. - Perturbed 24-hour sleep-wake cycle as evidenced by: delayed sleep onset; delayed sleep offset; disrupted sleep; high day-to-day variability of sleep-wake; non-restorative sleep; or daytime fatigue.
Exclusion criteria
- Receipt of other adjunctive antipsychotic medication for the current episode - Use of medications that affect sleep, melatonin, circadian rhythms or alertness - Evidence of other sleep, respiratory (e.g., sleep apnoea), neurological or primary medical conditions that could contribute to sleep-wake dysfunction - A primary psychotic diagnosis (e.g. schizophrenia) - Acute suicidal behaviour (score of 6 on Comprehensive Assessment of At-Risk Mental States (CAARMS) item 7.3) - Significant alcohol or other substance misuse or substance dependence - Regular shift-work within 60-days prior to entry into the study. - Recent transmeridian travel (participants will be required to wait three days for each jet lag hour before entering the study) - A history of previous hypersensitivity to brexpiprazole or any of the excipients. - Taking moderate to strong CYP2D6 or CYP3A4 inhibitors (e.g., quinidine, ketoconazole) or strong CYP3A4 inducers (e.g., rifampicin) - Pregnancy or lactation
Outcome results
None listed