Treatment Interrupts Depression Early

NCT05002309 | Recruiting Phase 2 DMC

• 1 other identifier: TIDE01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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 1:1 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-deficit/hyperactivity 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.

Conditions

Depression

Keywords

Severe mental illness

Outcome Measures

Primary Outcomes (3)

• Severity of depressive symptoms

  The primary outcome measure at Stage 1 will be the severity of depressive symptoms, indexed with the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The MADRS is scored on a scale from 0-60, the higher the score the higher the severity of symptoms.

  1-16 weeks

• Severity of depressive symptoms

  The primary outcome measure at Stage 2 will be the severity of depressive symptoms, indexed with the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The MADRS is scored on a scale from 0-60, the higher the score the higher the severity of symptoms.

  16-32 weeks

• Proportion of time spent depression free

  At Stage 3 follow-up, the primary outcome will be the proportion of time spent depression free, defined as a score of 1 or 0 on Longitudinal Interval Follow-up Evaluation (LIFE).

  16-104 weeks

Secondary Outcomes (9)

• Self-reported measure of depression.

  1-104 weeks

• Self-reported measure of generalized anxiety.

  1-104 weeks

• Self-reported measure of social anxiety.

  1-104 weeks

• Self-reported measures of general psychopathology.

  1-104 weeks

• Self-reported measure of quality of life.

  1-104 weeks

Other Outcomes (2)

• Functioning score

  1-104 weeks

• Developmental milestones achievement

  1-104 weeks

Study Arms (2)

Psychotherapy

EXPERIMENTAL

Cognitive-behavioural therapy

Behavioral: Cognitive-Behavioural Therapy

Pharmacotherapy

EXPERIMENTAL

Antidepressant medication

Drug: Antidepressant medication

Interventions

Cognitive-Behavioural Therapy BEHAVIORAL

20 sessions of individual CBT are offered over 16 weeks, conducted 1-on-1, with a trained and supervised therapist. Participants will learn about the cognitive, behavioural, emotional, and environmental factors which contribute to maintaining their depression. They will 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. Weekly "homework" will be used to maximize opportunities for practice and consolidation of new skills. The individual sessions can be combined with optional family/parent/partner 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 corresponds to evidence available for CBT for adolescents and young adults that is established as the best practice through rigorous trials.

Also known as: CBT

Psychotherapy

Antidepressant medication DRUG

The choice of antidepressants follows best-established evidence for treating depression in adolescents and young adults. We will offer treatment with fluoxetine, starting at 10mg a day, increasing to 20mg a day after 1 week if tolerated; a protocol established as safe and effective in adolescents and adults in multiple trials. Additional increases to 40 or 60mg will be possible based on positive effects and side-effects and clinical judgement, as recommended in this age group. In cases of intolerance or adverse reaction to fluoxetine, we will switch to sertraline (25-200mg) or escitalopram (5-20mg), two antidepressants licensed by the FDA for major depressive disorder in adolescents. Treatment will be optimized over 16 weeks, a time-frame comparable to the CBT arm. Pharmacotherapy will be managed and prescribed by qualified psychiatrists when starting treatment and reviewed after 1 week, 2 weeks and then in 2-weekly intervals for the remainder of the 16 weeks acute treatment period.

Also known as: ADM

Pharmacotherapy

Eligibility Criteria

• Age: 12 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 12-25 years
• Diagnosis of major depressive disorder, onset of the major depressive disorder within the last 12 months. Depression considered the most significant problem in need of treatment.
• Verbal ability sufficient to participate in psychological treatment.

You may not qualify if:

• Personal history of a manic or hypomanic episode, diagnosis of a psychotic disorder, pervasive developmental disorder or autism spectrum disorder, intellectual disability, mental disorders secondary to neurological or other medical condition, active substance use disorder.
• Previous trial of any treatment for major depressive disorder lasting 4 weeks or longer, current use of antipsychotic, antidepressant or mood-stabilizer medication.
• Recent (past 6 weeks) change in any psychotropic medication (including stimulants, hypnotics, anxiolytics) or receipt of 4 of more sessions of cognitive-behavioural therapy.
• Pregnancy or breastfeeding. If participants become pregnant or learn of pregnancies during the study, we will consult with Dr. Tanya Tulipan and jointly make the best decision for the participant with the option to either continue or end study treatment.
• No one will be excluded based on sex, gender, race, ethnicity, or living arrangements.

Sponsors & Collaborators

• Nova Scotia Health Authority: lead

Study Sites (2)

Nova Scotia Health

Halifax, Nova Scotia, B#H 2E2, Canada

RECRUITING

Centre intégré universitaire de santé et de services sociaux de l'Ouest-de-l'Île-de-Montréal / Centre de Recherche Douglas (Montreal West Island IUHSSC / Douglas Research Center)

Montreal, Quebec, H4H 1R3, Canada

RECRUITING

MeSH Terms

Conditions

Depression; Mental Disorders

Interventions

Cognitive Behavioral Therapy; Antidepressive Agents

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Rudolf Uher, MD, PhD

  Nova Scotia Health Authority

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rudolf Uher, MD, PhD

CONTACT

902-473-7209; uher@dal.ca

Jill Cumby, RN, MN

CONTACT

902-473-1781; jill.cumby@nshealth.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 12, 2021
• Study Start: December 2, 2021
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)