Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety

NCT ID: NCT02818751

Last Updated: 2020-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2020-05-31

Brief Summary

Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents with Anxiety. To determine the effects of escitalopram on functional activation patterns during a Continuous Performance Task with Emotional and Neutral Distracters, the CPT-END. To examine baseline functional activity and functional connectivity profiles in the ventrolateral prefrontal cortex as markers of subsequent treatment response to escitalopram in adolescents with generalized anxiety disorder (GAD). To use proton magnetic resonance spectroscopy (1H MRS) to examine glutamatergic and γ-aminobutyric acid (GABA)-related abnormalities in the anterior cingulate in adolescents with GAD as compared to healthy adolescents.

Detailed Description

The long-term goal of this study is to explore the neurobiological basis of generalized anxiety disorder (GAD) using a validated functional MRI (fMRI) paradigm and functional connectivity analyses with a cohort of GAD patients and healthy subjects and generating feasibility and preliminary data regarding treatment-related effects of escitalopram on brain functional activation and Fc patterns in pediatric GAD. An additional goal is to identify biological markers in saliva and urine that will predict treatment response in pediatric subjects with GAD. The central hypothesis of this proposal is that core dysfunction within the prefrontal-amygdala network, which the investigators and others have observed in GAD, will be normalized by successful treatment. The rationale underlying this hypothesis is that, despite the high prevalence of GAD, there is a need to understand its neurobiology and to identify biomarkers of treatment response and the mechanisms by which selective serotonin reuptake inhibitors (SSRIs) putatively effect changes in the neurocircuitry of pediatric GAD.

Conditions

Anxiety

Keywords

Anxiety; Adolescents with Anxiety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Escitalopram

Patients being randomized to receive escitalopram, at an initial dose of 5 mg (oral) daily for 2 days. On day 3, escitalopram will be increased to 10 mg daily and continued for 7 days. Then, on day 10, escitalopram will be increased to 15 mg. At the week 4 visit, the dose of escitalopram may be increased to 20 mg, based on the investigator's clinical judgment and if significant anxiety symptoms are still present.

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

Patients being randomized to receive escitalopram.

Placebo

Patients will receive placebo (sugar pill) at an initial dose of 5 mg daily for 2 days. On day 3, placebo will be increased to 10 mg daily and continued for 7 days to match the experimental group.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patients being randomized to receive placebo.

Healthy Controls

Healthy adolescents will receive fMRI scans at the same time points, which will provide assessments of the stability of neurophysiologic measures and will be used to adjust and interpret comparisons within the patients (i.e., whether patient values are changing toward or away from those of healthy adolescents).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Escitalopram

Patients being randomized to receive escitalopram.

Intervention Type: DRUG

Placebo

Patients being randomized to receive placebo.

Intervention Type: OTHER

Other Intervention Names

Lexapro; Sugar Pill

Eligibility Criteria

Inclusion Criteria

Inclusion - Anxiety Subjects:

• Diagnostic and Statistical Manual-IV (Text Revision) criteria for generalized anxiety disorder diagnosed by the Anxiety Disorders Interview Schedule (ADIS-IV)
• Baseline Pediatric Anxiety Rating Scale (PARS) score ≥15 at baseline
• Ages 12-17 years 11 months old
• Fluent in English
• Provision of written informed consent by a legal guardian and written assent by the subject
• Tanner scale stages II-V, in order to include only post-pubescent subjects and minimize brain changes associated with the onset of puberty
• Does not have a history of intolerance, non-response or hypersensitivity to escitalopram
• No co-occurring Diagnostic and Statistical Manual-IV (Text Revision) diagnosis mood (except dysthymia, depression not otherwise specified), eating, pervasive developmental disorder or psychotic disorders
• Subjects will be excluded if there are any lifetime diagnosis of mental retardation (intelligence quotient < 70)
• Subjects with any history of alcohol or drug dependence or any alcohol abuse within the past 6 months (nicotine dependence is permitted) will be excluded
• No new psychotherapy will be permitted during study participation and if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline
• Females will not be eligible to participate if pregnant, breast feeding or lactating.

Inclusion - Healthy Subjects:

• Ages of 12-17 years and 11 months
• No history of any Diagnostic and Statistical Manual-IV (Text Revision) Axis I disorders (nicotine dependence is permitted)
• No first-degree relatives with an affective or psychotic disorder
• No medications with central nervous system effects within 5 half-lives
• Fluent in English
• Tanner stage II-V
• Provision of informed consent and assent.

Exclusion Criteria

Exclusion - Generalized Anxiety Disorder Patients & Healthy Subjects:

• Contraindication to an magnetic resonance imaging (MRI) scan (e.g., braces or claustrophobia)
• An unstable medical or neurological illness that could influence fMRI or magnetic resonance spectroscopy results
• Subjects will be excluded if there are any lifetime diagnosis of mental retardation or intelligence quotient < 70)
• A positive pregnancy test
• Adolescents will be excluded for treatment with a medication with central nervous system effects that requires more than 5 days of a screening period in order to minimize the length of time between screening and baseline and maximize patient safety, while recognizing that a longer taper period is required of some medications
• Adolescents with any history of major medical or neurological disorders that may result in neurofunctional or neurochemical abnormalities including loss of consciousness for >10 minutes will be excluded
• No co-occurring Diagnostic and Statistical Manual-IV (Text Revision) diagnosis mood (other than dysthymia or Depression Not Otherwise Specified), eating, pervasive developmental disorder or psychotic disorders
• Subjects will be excluded if there are any lifetime diagnosis of mental retardation or intelligence quotient < 70
• Subjects with any history of alcohol or drug dependence or any alcohol abuse within the past 6 months (nicotine dependence is permitted) will be excluded
• No new psychotherapy will be permitted during study participation and if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline
• Females will not be eligible to participate if pregnant, breast feeding or lactating
• The patient lives >100 miles from the University of Cincinnati or is not able to attend follow-up visits

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Strawn, MD

Associate Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Strawn

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, United States

Countries

United States

References

Strawn JR, Mills JA, Schroeder H, Mossman SA, Varney ST, Ramsey LB, Poweleit EA, Desta Z, Cecil K, DelBello MP. Escitalopram in Adolescents With Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled Study. J Clin Psychiatry. 2020 Aug 25;81(5):20m13396. doi: 10.4088/JCP.20m13396.

Reference Type: RESULT

PMID: 32857933 (View on PubMed)

Lu L, Li H, Mills JA, Schroeder H, Mossman SA, Varney ST, Cecil KM, Huang X, Gong Q, Levine A, DelBello MP, Sweeny JA, Strawn JR. Greater Dynamic and Lower Static Functional Brain Connectivity Prospectively Predict Placebo Response in Pediatric Generalized Anxiety Disorder. J Child Adolesc Psychopharmacol. 2020 Dec;30(10):606-616. doi: 10.1089/cap.2020.0024. Epub 2020 Jul 24.

Reference Type: RESULT

PMID: 32721213 (View on PubMed)

Marusak HA, Zundel CG, Shakir T, Ely SL, Carpenter C, Shampine M, Tamimi R, Matsko M, Rogers S, Losiowski J, O'Mara E, Jaster AM, Sharma K, deRoon-Cassini TA, Hillard CJ, Schroeder HK, Mills JA, Strawn JR, Barcelona J. Circulating endocannabinoids in children and adolescents: associations with anxiety and the impact of selective serotonin reuptake inhibitors. Neuropsychopharmacology. 2025 Sep;50(10):1606-1614. doi: 10.1038/s41386-025-02155-7. Epub 2025 Jun 27.

Reference Type: DERIVED

PMID: 40579470 (View on PubMed)

Lu L, Li H, Baumel WT, Mills JA, Cecil KM, Schroeder HK, Mossman SA, Huang X, Gong Q, Sweeney JA, Strawn JR. Acute neurofunctional effects of escitalopram during emotional processing in pediatric anxiety: a double-blind, placebo-controlled trial. Neuropsychopharmacology. 2022 Apr;47(5):1081-1087. doi: 10.1038/s41386-021-01186-0. Epub 2021 Sep 27.

Reference Type: DERIVED

PMID: 34580419 (View on PubMed)

Lu L, Mills JA, Li H, Schroeder HK, Mossman SA, Varney ST, Cecil KM, Huang X, Gong Q, Ramsey LB, DelBello MP, Sweeney JA, Strawn JR. Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial. J Am Acad Child Adolesc Psychiatry. 2021 Oct;60(10):1309-1318. doi: 10.1016/j.jaac.2020.11.023. Epub 2021 Feb 4.

Reference Type: DERIVED

PMID: 33548492 (View on PubMed)

Other Identifiers

K23MH106037

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Strawn FiESTAA

Identifier Type: -

Identifier Source: org_study_id