None listed
Conditions
Brief summary
The aim of this NHMRC-funded study is to answer an important question in the treatment of moderate-to-severe youth depression: should antidepressant treatment be started as a first-line treatment, concurrent with psychotherapy? The question has taken on increased clinical importance in the wake of recent evidence questioning the efficacy and safety of antidepressants in young people, and the subsequent development of treatment guidelines for youth depression that provide only qualified support for their use. This proposal aims to address the need for studies of effective treatments for youth with moderate to severe major depressive disorder (MDD). Patients between the ages of 15 and 25 will be randomised to receive either (i) cognitive behavioural therapy (CBT) and fluoxetine, or (ii) CBT and placebo, for 12 weeks in a double-blind, randomised controlled trial (RCT), with followup to 26 weeks. This will be the first placebo-controlled study that has examined whether the addition of medication to CBT is a more effective strategy than the provision of CBT alone for the treatment of youth depression. The primary hypothesis is that young people with moderate to severe MDD will show greater improvement after 12 weeks of treatment with CBT and fluoxetine (CBT+FLX) compared to treatment with CBT and placebo (CBT+PBO). The primary outcome measure is change in the MontgomeryAsberg Depression Rating Scale (MADRS), an observerrated depression scale that is widely used in depression treatment trials, being both easy to administer and psychometrically sound (Montgomery & Asberg, 1979). Our secondary hypotheses are that the CBT+FLX group will show greater improvement compared to the CBT+PBO group on efficacy, functioning, quality of life, and safety measures at 12 weeks, but that the differences between groups will not be sustained at 26 weeks.
Interventions
Cognitive Behavioural Therapy (CBT) will be administered once a week, over a period of 12 weeks
Antidepressant fluoxetine hydrochloride or a placebo tablet will be administered in conjunction with CBT over a period of 12 weeks. The starting dose of fluoxetine or placebo will be 1 capsule or 20mg, administered orally. The dose may be increased at week 5 of the study to a maximum dose of 2 capsules or 40 mg.
Each treatment session will last 45 to 50 minutes. Typically, an individual CBT session
Cognitive Behavioural Therapy (CBT) will be administered once a week, over a period of 12 weeks Antidepressant fluoxetine hydrochloride or a placebo tablet will be administered in conjunction with CBT over a period of 12 weeks. The starting dose of fluoxetine or placebo will be 1 capsule or 20mg, administered orally. The dose may be increased at week 5 of the study to a maximum dose of 2 capsules or 40 mg. Each treatment session will last 45 to 50 minutes. Typically, an individual CBT session comprises 3 components. The first third of the session is devoted to reviewing the take-home practice activities and setting an agenda for the current session by reviewing mood, events, incidents or issues that have arisen during the previous week. The middle third of the session is devoted to the skill to be taught that week, linking it with any issues or incidents raised in the first third of the session. The final third of the session addresses issues that have been generated in the first third of the session, and plans are made for the next take-home practice activity. It is anticipated that all therapists will attend fortnightly supervision sessions with senior clinicians. The fidelity of CBT treatment will be assessed throughout the trial to ensure that the treatment delivered by the trial therapists adheres to the CBT manual. Each CBT session will be recorded, and the de-identified recording will be stored on the OYHRC secure server. A random session from the course of therapy for each participant will be independently rated by an expert CBT practitioner using specifically designed scales for measuring CBT fidelity Participants will commence on 1 tablet of fluoxetine 20 mg or 1 tablet of the placebo pill. The medication can be increased to fluoxetine 40 mg daily (or 2 placebo pills) if there has been a poor clinical response after the first 4 weeks. The medication will be prescribed by the treating doctor after the baseline visit has been completed and the participant has been randomised. The trial medications will be supplied on a 4-weekly basis by the RMH Royal Park Campus pharmacy, with a total of 3 dispensations per patient
Sponsors
Orygen Youth Health Research Centre
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
15 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
Aged between 15 and 25 years inclusive: Diagnosis of Major Depressive Disorder (MDD) using Structured Clinical Interview for DSM-IV Axis I Disorders, patient version (SCID); Score on the MADRS of 20 or greater, indicating depression of at least moderate severity; Ability to provide written informed consent
Exclusion criteria
First episode psychosis (at least one positive symptom occurring daily for at least one week, or at least three times per week if the symptom lasts for longer than one hour on each occasion); Lifetime or current SCID-I diagnosis of bipolar I or II disorder; Acute or unstable medical disorder that would interfere with treatment; Severe disturbance such that the young person would be unable to comply with the requirements of informed consent or comply with the study protocol; Current treatment with an antidepressant medication for at least 2 weeks; Previous treatment with fluoxetine that was either ineffective or poorly tolerated
Outcome results
None listed