Ignite Creation Date:
2024-05-06 @ 4:30 PM
Last Modification Date:
2024-10-26 @ 2:11 PM
Study NCT ID:
NCT05002309
Status:
RECRUITING
Last Update Posted:
2023-02-08
First Post:
2021-07-26
Brief Title:
Treatment Interrupts Depression Early
Sponsor:
Rudolf Uher
Organization:
Nova Scotia Health Authority
Study Overview
Official Title:
Treatment Interrupts Depression Early
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TIDE
Brief Summary:
The TIDE project aims to establish personal indicators for initial treatment choice for youth with first episode depression Specifically 100 adolescents and young adults age 12 to 25 with untreated major depressive disorder of recent onset will be randomly allocated in 11 ratio to one of two evidence-based regimens for youth depression A Individual cognitive-behavioural therapy and B Optimized pharmacological treatment with an antidepressant All participants will be offered active treatment for up to 1 year and follow-up for 2 years to establish short- and long-term outcomes including change in depressive symptoms maintenance of remission core role functioning achievement of educational occupational and social milestones and quality of life Baseline characteristics including duration of untreated depression pre-existing anxiety attention-deficithyperactivity disorder substance use symptoms of reduced interest and activity sleep rhythm and melody of speech brain function history of childhood adversity coping style repetitive thinking and family history of depression and bipolar disorder will be tested as potential moderators of outcome Characteristics that differentially predict outcomes in those allocated to initial cognitive-behavioural therapy and those allocated to initial treatment with antidepressants will be combined into a personalized allocation algorithm
Detailed Description:
Design TIDE is an open-label randomized trial with two parallel arms and long-term follow-up
Participants Youth and young adults with major depressive disorder will participate
Recruitment Young people aged 12 to 25 will be recruited through family physicians child and adolescent mental health services NSHA IWK Central referral student health traditional advertisement posters and social media advertisement Instagram Facebook Reddit and Twitter
Random allocation Consenting eligible participants will be randomly allocated in 11 ratio to intervention A cognitive-behavioral therapy or intervention B optimized antidepressant treatment by an independent statistician using random blocks block size 4 to 8 stratified by participant age 18 18 The allocation sequence will be held by a statistician at a separate location the Research Methods Unit and will remain concealed from the assessment and treatment team until the baseline assessment is completed
Interventions It is our aim to personalize the choice between established active treatments not to test an active treatment against an inactive control Therefore the investigator will offer every participant entering the study an intervention that is established as safe and effective Within the established interventions the investigator chose two that have the largest amount of evidence for efficacy cognitive-behavioural therapy and the antidepressant fluoxetine These two interventions are at equipoise meaning that the investigator has equally high expectation of treatment success from both approaches Yet the two treatment strategies represent distinct choices with intervention A relying on intensive psychological treatment and intervention B on optimized delivery of the best-established medication treatment for depression in youth
Because the first episode of depression is a dynamic state with a variety of outcomes the intervention will proceed in stages
Stage 0 Lead in Participants may enter the study at different stages of the first episode onset with some starting at a point where the indications for treatment or eligibility criteria are uncertain or at a time when the participant is undecided on whether they need or want to start active treatment To accommodate these early stages there is a lead-in of 1-4 weeks to establish the diagnosis assess severity and support the participant while deciding on whether they want to start active treatment This stage will include up to four weekly meeting with a clinician psychiatrist psychologist or CBT therapist that may involve information gathering information provision risk monitoring and supportive contact but no cognitive-behavioural therapy or pharmacotherapy If the participant and the clinician agree that treatment is indicated the participant can transition to Stage 1 active intervention Stage 0 is not randomized If the participant recovers and no longer meets inclusion criteria or decides that they do not need active treatment they may transition directly to Stage 3 Follow-up
Stage1 Active interventions At this stage all participants will be offered active treatment for depression Radom allocation will occur at the beginning of Stage 1 and will determine whether the participant is offered Intervention A or Intervention B
Intervention A Cognitive-behavioural therapy CBT This intervention starts with a course of 20 sessions of individual CBT offered over 16 weeks The sessions will be conducted one-on-one with a trained and supervised CBT therapist giving full attention to one participant at a time Over the course of treatment participants will develop an understanding of the cognitive behavioural emotional and environmental factors which contribute to maintaining their depression They will learn and apply skills to interrupt unhelpful cognitive and behavioural patterns and engage in guided exploration to improve self-understanding CBT is a structured and collaborative treatment and as such each session will follow a similar pattern and commence with a collaboratively set agenda Weekly homework will be used to maximize opportunities for practice and consolidation of new skills with the aim of the participant being able to apply these skills well beyond the termination of therapy The individual sessions can be combined with optional familyparentpartner sessions depending on the situation and preferences of the participant All sessions will be video-recorded to allow high-quality supervision fidelity- and quality-assurance This way of delivery corresponds to the best evidence available for CBT for adolescents and young adults that is established as the best practice through rigorous trials
Intervention B Antidepressant pharmacotherapy The choice of antidepressants follows the best established evidence for treating depression in adolescents and young adults The investigator will initially offer treatment with fluoxetine starting at 10mg once daily and increasing to 20mg once daily after one week if tolerated a protocol established as safe and effective in both adolescents and adults across multiple trials Additional dose increases to 40 or 60mg will be possible based on balance of positive effects and side-effects and clinical judgement consistent with recommendations in this age group In cases of intolerance or adverse reaction to fluoxetine the investigator will switch to sertraline 25 to 200mg or escitalopram 5 to 20mg the other two antidepressants licensed by the Food and Drug Administration for major depressive disorder in adolescents The treatment with fluoxetine or sertraline or escitalopram will be optimized over 16 weeks a time-frame comparable to the CBT intervention The investigator expects that most participants will only use the antidepressant for as long as required to minimized overall exposure to pharmacotherapy Pharmacotherapy will be managed and prescribed by qualified psychiatrists referred to as pharmacotherapists through this protocol The pharmacotherapist will hold appointments when starting the treatment after 1 week two weeks and then in two-weekly intervals for the reminder of the 16 weeks acute treatment period
Stage 2 Continuation treatment and cross-over options After completion of a course of CBT or antidepressant further decisions depend on the outcome of the initial treatment and will be personalized based on a discussion between the participant and a clinician If a full remission of depression is achieved the next stage may involve continuation of the same treatment up to 4 booster sessions of CBT continued treatment with an antidepressant If a remission is not achieved the best recommended next step is the cross-over to or the addition of the other established treatment Therefore participants who received CBT in Stage 1 and did not reach remission will be offered treatment with an antidepressant and participants who received the antidepressant in Stage 1 will be offered CBT The decision of whether to continue Stage 1 treatment will be based on the balance of benefits and adverse effects for the participant Participants who started antidepressant in Stage 1 and did not achieve full remission may decide to continue the antidepressant while also receiving CBT or to stop the antidepressant with coordinated support from the pharmacotherapist and the CBT therapist
Stage 3 Follow-up The investigators will follow participants once every 3 months for up to 2 years The purpose of this follow-up stage is to monitor the stability of remission and functional outcomes If the investigators identify re-emergence of depressive symptoms the investigators will offer Stage 2 interventions or appropriate clinical referral as appropriate based on consultation with the principal investigator or other qualified psychiatrist For participants who do not achieve remission in stages 1 and 2 the clinically advisable next steps may involve augmentation with additional treatment Such augmentation treatment is beyond the scope of the present protocol Participants will be allowed to remain in the follow-up stage even if they receive additional treatment through regular clinical services or additional studies
Participants Youth and young adults with major depressive disorder will participate
Recruitment Young people aged 12 to 25 will be recruited through family physicians child and adolescent mental health services NSHA IWK Central referral student health traditional advertisement posters and social media advertisement Instagram Facebook Reddit and Twitter
Random allocation Consenting eligible participants will be randomly allocated in 11 ratio to intervention A cognitive-behavioral therapy or intervention B optimized antidepressant treatment by an independent statistician using random blocks block size 4 to 8 stratified by participant age 18 18 The allocation sequence will be held by a statistician at a separate location the Research Methods Unit and will remain concealed from the assessment and treatment team until the baseline assessment is completed
Interventions It is our aim to personalize the choice between established active treatments not to test an active treatment against an inactive control Therefore the investigator will offer every participant entering the study an intervention that is established as safe and effective Within the established interventions the investigator chose two that have the largest amount of evidence for efficacy cognitive-behavioural therapy and the antidepressant fluoxetine These two interventions are at equipoise meaning that the investigator has equally high expectation of treatment success from both approaches Yet the two treatment strategies represent distinct choices with intervention A relying on intensive psychological treatment and intervention B on optimized delivery of the best-established medication treatment for depression in youth
Because the first episode of depression is a dynamic state with a variety of outcomes the intervention will proceed in stages
Stage 0 Lead in Participants may enter the study at different stages of the first episode onset with some starting at a point where the indications for treatment or eligibility criteria are uncertain or at a time when the participant is undecided on whether they need or want to start active treatment To accommodate these early stages there is a lead-in of 1-4 weeks to establish the diagnosis assess severity and support the participant while deciding on whether they want to start active treatment This stage will include up to four weekly meeting with a clinician psychiatrist psychologist or CBT therapist that may involve information gathering information provision risk monitoring and supportive contact but no cognitive-behavioural therapy or pharmacotherapy If the participant and the clinician agree that treatment is indicated the participant can transition to Stage 1 active intervention Stage 0 is not randomized If the participant recovers and no longer meets inclusion criteria or decides that they do not need active treatment they may transition directly to Stage 3 Follow-up
Stage1 Active interventions At this stage all participants will be offered active treatment for depression Radom allocation will occur at the beginning of Stage 1 and will determine whether the participant is offered Intervention A or Intervention B
Intervention A Cognitive-behavioural therapy CBT This intervention starts with a course of 20 sessions of individual CBT offered over 16 weeks The sessions will be conducted one-on-one with a trained and supervised CBT therapist giving full attention to one participant at a time Over the course of treatment participants will develop an understanding of the cognitive behavioural emotional and environmental factors which contribute to maintaining their depression They will learn and apply skills to interrupt unhelpful cognitive and behavioural patterns and engage in guided exploration to improve self-understanding CBT is a structured and collaborative treatment and as such each session will follow a similar pattern and commence with a collaboratively set agenda Weekly homework will be used to maximize opportunities for practice and consolidation of new skills with the aim of the participant being able to apply these skills well beyond the termination of therapy The individual sessions can be combined with optional familyparentpartner sessions depending on the situation and preferences of the participant All sessions will be video-recorded to allow high-quality supervision fidelity- and quality-assurance This way of delivery corresponds to the best evidence available for CBT for adolescents and young adults that is established as the best practice through rigorous trials
Intervention B Antidepressant pharmacotherapy The choice of antidepressants follows the best established evidence for treating depression in adolescents and young adults The investigator will initially offer treatment with fluoxetine starting at 10mg once daily and increasing to 20mg once daily after one week if tolerated a protocol established as safe and effective in both adolescents and adults across multiple trials Additional dose increases to 40 or 60mg will be possible based on balance of positive effects and side-effects and clinical judgement consistent with recommendations in this age group In cases of intolerance or adverse reaction to fluoxetine the investigator will switch to sertraline 25 to 200mg or escitalopram 5 to 20mg the other two antidepressants licensed by the Food and Drug Administration for major depressive disorder in adolescents The treatment with fluoxetine or sertraline or escitalopram will be optimized over 16 weeks a time-frame comparable to the CBT intervention The investigator expects that most participants will only use the antidepressant for as long as required to minimized overall exposure to pharmacotherapy Pharmacotherapy will be managed and prescribed by qualified psychiatrists referred to as pharmacotherapists through this protocol The pharmacotherapist will hold appointments when starting the treatment after 1 week two weeks and then in two-weekly intervals for the reminder of the 16 weeks acute treatment period
Stage 2 Continuation treatment and cross-over options After completion of a course of CBT or antidepressant further decisions depend on the outcome of the initial treatment and will be personalized based on a discussion between the participant and a clinician If a full remission of depression is achieved the next stage may involve continuation of the same treatment up to 4 booster sessions of CBT continued treatment with an antidepressant If a remission is not achieved the best recommended next step is the cross-over to or the addition of the other established treatment Therefore participants who received CBT in Stage 1 and did not reach remission will be offered treatment with an antidepressant and participants who received the antidepressant in Stage 1 will be offered CBT The decision of whether to continue Stage 1 treatment will be based on the balance of benefits and adverse effects for the participant Participants who started antidepressant in Stage 1 and did not achieve full remission may decide to continue the antidepressant while also receiving CBT or to stop the antidepressant with coordinated support from the pharmacotherapist and the CBT therapist
Stage 3 Follow-up The investigators will follow participants once every 3 months for up to 2 years The purpose of this follow-up stage is to monitor the stability of remission and functional outcomes If the investigators identify re-emergence of depressive symptoms the investigators will offer Stage 2 interventions or appropriate clinical referral as appropriate based on consultation with the principal investigator or other qualified psychiatrist For participants who do not achieve remission in stages 1 and 2 the clinically advisable next steps may involve augmentation with additional treatment Such augmentation treatment is beyond the scope of the present protocol Participants will be allowed to remain in the follow-up stage even if they receive additional treatment through regular clinical services or additional studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None