TDM-Guided Treatment With SSRIs in Hospitalized Adults and Children

NCT07478796 | Recruiting Phase 4

• 1 other identifier: 213/25
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Depression in childhood and adolescence is a serious and increasing public-health problem associated with profound short- and long-term consequences, including impaired social and educational functioning, increased risk of somatic illness and substance use, and elevated mortality from suicide. Up to half of depressive disorders beginning in youth persist into adulthood, and the COVID-19 pandemic, with its attendant social isolation, has further increased the incidence of clinically significant depressive illness in children and young adults. Despite the high burden of disease, pharmacotherapeutic guidance for pediatric depression remains limited. Selective serotonin reuptake inhibitors (SSRIs) are first-line agents, yet dosing recommendations for youth do not adequately account for major sources of variability such as developmental pharmacokinetics, body size, age, comorbid diagnoses, and pharmacogenetic differences. Fluoxetine is commonly recommended in pediatric populations largely for historical reasons, while newer SSRIs such as escitalopram and sertraline are increasingly prescribed off-label without robust comparative evidence. This randomized clinical trial evaluates therapeutic drug monitoring (TDM)-guided treatment with fluoxetine, sertraline, or escitalopram in children and adults diagnosed with Major Depressive Disorder. TDM procedures will be implemented across all randomized arms to capture drug exposure and enable dose adjustments according to predefined safety and efficacy criteria. Treatments will be initiated at the lower end of recommended pediatric doses and titrated if prespecified clinical nonresponse or tolerability thresholds are met, allowing evaluation of dose-response dynamics while prioritizing patient safety. The study combines prospective, randomized comparative effectiveness methodology with intensive pharmacokinetic/pharmacodynamic (PK/PD) assessment. Repeated plasma concentration measurements will be collected at multiple timepoints to characterize within- and between-patient PK variability for each SSRI. Standardized clinical instruments will be used longitudinally to assess depressive symptom severity, response and remission rates, time to onset of therapeutic effect, adverse events (including early activation and worsening of suicidal ideation), treatment adherence, and functional outcomes (academic performance, social functioning, and quality of life). Pharmacogenetic testing will be performed to evaluate the contribution of genetic variants (including but not limited to CYP enzymes, serotonin transporter and MAO-A related polymorphisms) to PK parameters and clinical response. Integrated population PK and PK/PD modeling will (1) quantify concentration-effect and concentration-adverse-effect relationships over time, (2) identify demographic, clinical and genetic moderators of exposure and response, (3) evaluate nonlinearity in PK (e.g., dose-dependent absorption or clearance patterns), and (4) derive evidence-based therapeutic concentration ranges and individualized dosing algorithms for pediatric practice. Secondary objectives include head-to-head comparison of efficacy, tolerability, time to response, and persistence on treatment between the three SSRIs, as well as exploratory analyses of diagnostic subtypes and comorbidities that may influence outcomes. By filling critical gaps in controlled PK/PD data for the most commonly prescribed SSRIs in youth, this trial aims to move beyond meta-analytic inference toward actionable, individualized dosing recommendations. The expected outcomes are earlier identification of atypical pharmacokinetics, safer and more effective dose optimization, reduced adverse events and early discontinuation, shortened time to symptomatic improvement, and ultimately improved functional recovery and quality of life for children and young adults with depression. The study's translational PK/PD outputs will inform clinical TDM protocols, pediatric dosing guidelines, and future precision-medicine strategies in adolescent psychopharmacology.

Conditions

Depression - Major Depressive Disorder; Depressive Episodes

Keywords

Therapeutic Drug Monitoring (TDM); SSRI; Pharmacokinetics; Pharmacodynamics; Personalized Medicine; Pediatrics; Adolescents; Fluoxetine; Escitalopram; Sertraline; Biomarkers

Outcome Measures

Primary Outcomes (2)

• Change in Depression Severity (CDI)

  Change in depression severity score from Baseline to Week 8 using the Children's Depression Inventory (CDI) for adolescents (12-17 years). The CDI is a 27-item scale. Total scores range from 0 to 54. Higher scores indicate more severe depressive symptoms (a worse outcome).

  Baseline and Week 8

• Change in Depression Severity (MADRS)

  Change in depression severity score from Baseline to Week 8 using the Montgomery-Asberg Depression Rating Scale (MADRS) for adults. The MADRS is a 10-item questionnaire. Total scores range from 0 to 60. Higher scores indicate greater depression severity (a worse outcome).

  Baseline and Week 8

Secondary Outcomes (6)

• Therapeutic Drug Concentration (PK)

  14 timepoints over 8 weeks (T0 to T13)

• Incidence of Treatment-Emergent Adverse Events (UKU Scale)

  Weekly from Baseline through Week 8

• Changes in Molecular and Biochemical Biomarker Levels

  Baseline and Week 8

• Change in Global Illness Severity and Improvement (CGI)

  Baseline through Week 8 (assessed weekly)

• Change in Anxiety Symptoms (STAI)

  Baseline through Week 8 (assessed weekly)

Study Arms (3)

Fluoxetine Group

ACTIVE COMPARATOR

Oral Fluoxetine once daily. Initial dose: 10 mg (children/adolescents/elderly \>64y) or 20 mg (adults 18-64y). Dose may be increased after 3 weeks in case of non-response (\<25% improvement).

Drug: Fluoxetine

Escitalopram Group

ACTIVE COMPARATOR

Oral Escitalopram once daily. Initial dose: 5 mg (children/adolescents/elderly \>64y) or 10 mg (adults 18-64y). Dose may be increased after 3 weeks in case of non-response (\<25% improvement)

Drug: Escitalopram

Sertraline Group

ACTIVE COMPARATOR

Oral Sertraline once daily. Initial dose: 25 mg (children/adolescents/elderly \>64y) or 50 mg (adults 18-64y). Dose may be increased after 3 weeks in case of non-response (\<25% improvement).

Drug: Sertralin

Interventions

Fluoxetine DRUG

Oral fluoxetine administered once daily in the morning. Dosing is stratified by age: Children/adolescents (12-17 years) and elderly (\>64 years) start at 10 mg/day; adults (18-64 years) start at 20 mg/day. If clinical improvement is \<25% after 3 weeks, the dose is escalated to 20 mg/day for children/elderly and 40 mg/day for adults. Treatment duration is 8 weeks, with therapeutic drug monitoring (TDM) performed weekly to assess plasma concentrations.

Fluoxetine Group

Escitalopram DRUG

Oral escitalopram administered once daily in the morning. Dosing is stratified by age: Children/adolescents (12-17 years) and elderly (\>64 years) start at 5 mg/day; adults (18-64 years) start at 10 mg/day. If clinical improvement is \<25% after 3 weeks, the dose is escalated to 10 mg/day for children/elderly and 20 mg/day for adults. Treatment duration is 8 weeks, with therapeutic drug monitoring (TDM) performed weekly to assess plasma concentrations.

Escitalopram Group

Sertralin DRUG

Oral sertraline administered once daily in the morning. Dosing is stratified by age: Children/adolescents (12-17 years) and elderly (\>64 years) start at 25 mg/day; adults (18-64 years) start at 50 mg/day. If clinical improvement is \<25% after 3 weeks, the dose is escalated to 50 mg/day for children/elderly and 100 mg/day for adults. Treatment duration is 8 weeks, with therapeutic drug monitoring (TDM) performed weekly to assess plasma concentrations.

Sertraline Group

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female gender.
• Age 12 years or older.
• Diagnosis of moderate or severe depressive episode requiring SSRI treatment (fluoxetine, escitalopram, or sertraline).
• Written informed consent provided by patient and/or legal guardian.
• Women of childbearing potential must agree to use effective contraception or sexual abstinence.

You may not qualify if:

• Pregnancy, breastfeeding, or planning pregnancy.
• Diagnosis of other mental disorders (schizophrenia, bipolar disorder, intellectual disability).
• Decompensated severe somatic disorders (e.g., endocrine disorders, asthma exacerbation, hepatic/renal failure).
• Treatment with fluoxetine, sertraline, or escitalopram at an adequate dose for at least 4 weeks for the current episode (unless washout of 5x half-life is observed).
• Use of medications with high risk of CYP enzyme interactions.

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead

Study Sites (1)

Szpital Kliniczny im. Karola Jonschera UMP (Poznan University of Medical Sciences)

Poznan, Greater Poland Voivodeship, 60-572, Poland

RECRUITING

Related Publications (14)

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MeSH Terms

Interventions

Fluoxetine; Escitalopram

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, open-label, active-controlled trial with three parallel arms.

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: March 18, 2026
• Study Start: April 3, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will become available following the publication of the primary study results and the completion of the project (anticipated November 2027).
• Access Criteria: Anonymized data will be available as supplementary data for the manuscripts. For more detailed data, access requests will be reviewed to ensure compliance with ethical guidelines and data protection regulations (GDPR/RODO).

Locations

PL (1)