Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth

NCT02553161 | Completed DMC

• 2 other identifiers: DelBello/Singh AIMR01MH105469
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 2

Brief Summary

A 16-week double blind, placebo-controlled investigation of escitalopram in adolescents with depression and/or anxiety with a family history of Bipolar Disorder. Subjects will be evaluated using semi-structured diagnostic interviews and symptom ratings, participate in a MRI scan and then randomized to treatment. Following randomization, high-risk youth will have visits every week for the first 4 weeks of treatment then biweekly up to 16 weeks during which time tolerability and ratings will be performed. MRI scan will be repeated at week 4.

Conditions

Depression; Anxiety; Bipolar Disorder

Keywords

Depression

Outcome Measures

Primary Outcomes (1)

• Baseline-endpoint change in prefrontal-amygdala functional connectivity by Scan.

  Study the neural mechanisms of antidepressant-related dysfunctional arousal by ensuring that the treatment assignment precedes the 4-week scan, and the 4-week scan precedes the assessment of highest arousal measured between 4 and 16 weeks.The change in amygdala hyperactivity from the baseline to 4-week scan will be treated as the outcome and the treatment status (MED vs. No MED) will be treated as the predictor variable. The primary outcome is the level of post-treatment arousal (highest after the 4-week scan). The early change (baseline to 4 weeks) in amygdala hyperactivity, treatment assignment (MED vs. No MED), and the interaction between the two will be the predictors of arousal.

  Baseline to 16 weeks

Secondary Outcomes (1)

• Week 4- endpoint change in mood by and arousal ratings

  Between week 4 and 16

Study Arms (3)

MED - Escitalopram with psychotherapy

EXPERIMENTAL

Youth will also be assigned a board certified child psychiatrist (Drs. Singh or Chang at Stanford; Drs. DelBello or Patino at UC), who will be blind to treatment condition and see youth weekly for the first 4 weeks, then biweekly until 16 weeks. Youth in the MED condition will be given the USFDA (US Food \& Drug Administration) approved antidepressant, escitalopram for the treatment of depression or anxiety in youth and follow a standard dose titration schedule of 5 mg/day for 1 week, 10mg/day for 1 week, then with a target dose of 20-30 mg/day by 4 weeks.

Drug: Escitalopram

No MED -Psychotherapy

PLACEBO COMPARATOR

All participants (No MED and MED) will be assigned a study-trained therapist who will provide hour-long weekly individual cognitive behavioral psychotherapy (CBT) based on current evidence-based practices for the treatment of anxiety and depressive symptoms for youth.

Behavioral: Cognitive behavioral Psychotherapy

Healthy Control

NO INTERVENTION

60 (30 at Stanford, 30 at University of Cincinnati) 12- to 17-year old male and female typically developing healthy controls. Healthy controls will receive behavioral, neural, and physiological assessments at baseline only. healthy controls will be scanned at baseline only and serve as a reference group to determine whether MRI changes observed in the high-risk group from baseline to week 4 are toward or away from normal.

Interventions

Escitalopram DRUG

Youth in the MED condition will be given the USFDA approved antidepressant, escitalopram for the treatment of depression or anxiety in youth and follow a standard dose titration schedule of 5 mg/day for 1 week, 10mg/day for 1 week, then with a target dose of 20-30 mg/day by 4 weeks. Titration will be no faster than 5mg/week. This titration guideline was drawn from the escitalopram package insert for pediatric dosing, which states that target doses may be achieved by 4 weeks.

Also known as: Lexapro

MED - Escitalopram with psychotherapy

Cognitive behavioral Psychotherapy BEHAVIORAL

All participants (No MED and MED) will be assigned a study-trained therapist who will provide hour-long weekly individual cognitive behavioral psychotherapy (CBT) based on current evidence-based practices for the treatment of anxiety and depressive symptoms for youth.

Also known as: CBT

No MED -Psychotherapy

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• age 12 years, 0 mos. - 17 years, 11 mos.;
• at least one parent or step-parent/guardian with whom the subject lives is willing to participate in research sessions;
• the child and relative(s) are able and willing to give written informed assent/consent to participate, respectively;
• the youth meets criteria for high-risk:
• has at least one first degree relative with Bipolar I Disorder, as assessed by the Structured Clinical Interview for DSM (SCID; First et al. 1995), the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-PL, Kaufman et al., 1997), and the Family History-Research Diagnostic Criteria (FH-RDC; Andreasen et al., 1977);
• the youth shows evidence of current significant depressive or anxiety symptoms as determined by a current Childhood Depression Rating Scale-Revised (CDRS-R, Poznanski et al.,1984) score \> 35 and/or a current Pediatric Anxiety Rating Scale (PARS, 2002) score \> 15.
• age 12 years, 0 mos. - 17 years, 11 mos.;
• at least one parent or step-parent/guardian with whom the subject lives is willing to participate in research sessions;
• the child and relative(s) are able and willing to give written informed assent/consent to participate, respectively;
• no personal or family history of any psychopathology as assessed by the KSADS-PL structured clinical interview (Kaufman et al., 1997) and the Family History-Research Diagnostic Criteria (FH-RDC; Andreasen et al., 1977).

You may not qualify if:

• any history of syndromal bipolar I or II disorder (i.e., history of mania, mixed episode, or major depression with hypomania);
• a history of previous antidepressant exposure
• a DSM-5 diagnosis of autism, pervasive developmental disorder, OCD(Obsessive-Compulsive Disorder), PTSD, Tourette's disorder, or any psychotic disorder including schizophrenia;
• evidence of mental retardation (IQ \< 70) as determined by the Weschler Abbreviated Scale of Intelligence (WASI; Psychological Corporation, 1999);
• comorbid neurologic diseases such as seizure disorder;
• Drug or alcohol abuse or dependence disorders in the 4 months prior to study recruitment, although a lifetime history of substance or alcohol disorders can be present if the child has been abstinent for at least 6 months (see further discussion below);
• evidence of an unstable medical or psychiatric disorder that requires immediate hospitalization or other emergency medical treatment;
• a positive pregnancy test; participants will be encouraged but not mandated to discuss a positive pregnancy test with their guardians and we will follow local laws.
• any contraindication for MRI, including metal in the body related to an injury or surgery (e.g., surgical clips, metal fragments in the eyes), piercings that cannot be removed, braces, or permanent retainers.

Sponsors & Collaborators

• University of Cincinnati: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Stanford University

Stanford, California, 94305-2004, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Related Publications (1)

• Honeycutt DC, Blom TJ, Ramsey LB, Strawn JR, Bruns KM, Welge JA, Patino LR, Singh MK, DelBello MP. Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study. J Child Adolesc Psychopharmacol. 2024 Feb;34(1):42-51. doi: 10.1089/cap.2023.0073.

  PMID: 38377518 DERIVED

MeSH Terms

Conditions

Depression; Anxiety Disorders; Bipolar Disorder

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders; Bipolar and Related Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Melissa P DelBello, MD, MS

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Manpreet K Singh, MD,MS

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: September 17, 2015
• Study Start: December 1, 2015
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2022
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)