Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD)

Official title

Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD): a Pragmatic Clinical Trial

Overview

This project aims to investigate the effectiveness of existing common antidepressants and to provide new evidence for depressed children and adolescents who are not responding to their first treatment.

Detailed description

This is an open-label Sequential Multiple Assignment Randomized Trial (SMART) of 16 weeks duration with two levels, each stage 8 weeks. In phase 1, adolescents with MDD will be selected into fluoxetine or fluoxetine combination CBT therapy groups and the choice of treatment will be at the discretion of the patient. Subjects who fail to respond will enter phase 2 randomization， where patients will be randomly assigned to oral sertraline, votioxetine, duloxetine or adding one of aripiprazole, lithium carbonate, and olanzapine to fluoxetine. The primary outcome of the treatment phase is the treatment remission rate and response rate. Secondary outcomes included: symptom scale; Quality of life; Sleep therapy; Symptoms of anxiety; Rumination and safety assessment.

Interventions

• Drug Fluoxetine
  Commonly used oral antidepressant.
• Drug Sertraline
  Commonly used oral antidepressant.
• Drug Vortioxetine
  Commonly used oral antidepressant.
• Drug Duloxetine
  Commonly used oral antidepressant.
• Drug Aripiprazole
  Commonly used oral augmentation therapy for antidepressants
• Drug Lithium Carbonate
  Commonly used oral augmentation therapy for antidepressants.
• Drug Olanzapine
  Commonly used oral augmentation therapy for antidepressants.
• Behavioral GCBT
  Commonly used intervention therapy of psychotherapy.

Primary outcome measures

• Change in CDRS-R (Children's Depression Rating Scale) scores from baseline [Time frame: Baseline of treatment period, 2 weeks, 1 month, 2 months, 3 months，4months; The follow-up period was 1 month, 3 months, 6 months and 12 months]

Secondary outcome measures (9)

• Change in BDI-II (Baker Depression Scale) scores from baseline [Time frame: Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
• Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline [Time frame: Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
• Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale) [Time frame: Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
• Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline [Time frame: Baseline of treatment period, 2 month, 4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
• Change in PedsQL4.0 (The Pediatric Quality of Life Inventory) scores from baseline [Time frame: Baseline of treatment period, 2 month, 4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
• Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline [Time frame: Baseline of treatment period, 1 month, 2 months, 3 months，4 months.]
• Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline [Time frame: The treatment period was 1 month, 2 months, 3 months，4 months.]
• Change in RSS (Ruminative Responses Scale) [Time frame: The treatment period was 1 month, 2 months.]
• Change in HCL-32（Hypomania Symptom Checklist-32） [Time frame: Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]

Eligibility criteria

Inclusion criteria

• Age 13 - 18
• As assessed by K-SADS-PL, it meets the DSM-V criteria for MDD with non-psychotic symptoms
• Score≥40 on the CDRS-R
• Participants with suicidal ideation are eligible, as long as clinicians consider outpatient treatment to be safe
• Sufficient audio-visual level to complete this study
• Written informed consent was obtained from patients and at least one of their parents

Exclusion criteria

• History of bipolar disorder, schizophrenia, autism, eating disorders, primary obsessive compulsive disorder, pervasive developmental disorder, or psychosis not otherwise specified
• History of serious physical illnesses
• Substance abuse or dependence
• Current depressive episode with clear suicidal plans or suicidal behavior
• Requires inpatient treatment for psychiatric disorders
• Severe mental disorders requiring
• 2 or more failed trials of antidepressant drugs: each trial for at least 8 weeks, with the last 4 weeks at full dose (e.g. fluoxetine 40mg/d, citalopram 40mg/d, escitalopram 20mg/d, sertraline 150mg/d )
• History of clear-cut intolerability of, or lack of effect with, an adequate trial of at least one protocol treatment option
• Taking any medicine that contraindicates in combination with or interferes with the efficacy of the treatment
• Taking or administering antidepressants within 5 half-lives
• Received modified electroconvulsive therapy within 12 months
• If female, is pregnant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Chongqing Medical University — Chongqing

Publications

• Gunlicks-Stoessel M, Mufson L, Bernstein G, Westervelt A, Reigstad K, Klimes-Dougan B, Cullen K, Murray A, Vock D. Critical Decision Points for Augmenting Interpersonal Psychotherapy for Depressed Adolescents: A Pilot Sequential Multiple Assignment Randomized Trial. J Am Acad Child Adolesc Psychiatry. 2019 Jan;58(1):80-91. doi: 10.1016/j.jaac.2018.06.032. Epub 2018 Oct 27. PMID 30577943
• Hawton K, van Heeringen K. Suicide. Lancet. 2009 Apr 18;373(9672):1372-81. doi: 10.1016/S0140-6736(09)60372-X. PMID 19376453
• van Ettekoven KM, Rasing SPA, Vermulst AA, Engels RCME, Kindt KCM, Creemers DHM. Cross-Lagged Associations between Depressive Symptoms and Response Style in Adolescents. Int J Environ Res Public Health. 2020 Feb 21;17(4):1380. doi: 10.3390/ijerph17041380. PMID 32098035
• Twenge JM, Cooper AB, Joiner TE, Duffy ME, Binau SG. Age, period, and cohort trends in mood disorder indicators and suicide-related outcomes in a nationally representative dataset, 2005-2017. J Abnorm Psychol. 2019 Apr;128(3):185-199. doi: 10.1037/abn0000410. Epub 2019 Mar 14. PMID 30869927
• McCarty CA, Weisz JR. Effects of psychotherapy for depression in children and adolescents: what we can (and can't) learn from meta-analysis and component profiling. J Am Acad Child Adolesc Psychiatry. 2007 Jul;46(7):879-86. doi: 10.1097/chi.0b013e31805467b3. PMID 17581452
• Birmaher B, Brent D; AACAP Work Group on Quality Issues; Bernet W, Bukstein O, Walter H, Benson RS, Chrisman A, Farchione T, Greenhill L, Hamilton J, Keable H, Kinlan J, Schoettle U, Stock S, Ptakowski KK, Medicus J. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry. 2007 Nov;46(11):1503-26. doi: 10.1097/ch PMID 18049300
• Luxton R, Kyriakopoulos M. Depression in children and young people: identification and management NICE guidelines. Arch Dis Child Educ Pract Ed. 2022 Feb;107(1):36-38. doi: 10.1136/archdischild-2020-320020. Epub 2021 May 10. No abstract available. PMID 33972346
• MacQueen GM, Frey BN, Ismail Z, Jaworska N, Steiner M, Lieshout RJ, Kennedy SH, Lam RW, Milev RV, Parikh SV, Ravindran AV; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Can J Psychiatry. 2016 Sep;61(9):588-603 PMID 27486149

Identifiers

NCT: NCT05814640 · 1stChongqingMU--ZXY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗