Personalized Escitalopram Dosing in Patients With Depression

NCT ID: NCT05210140

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 148 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-07-16
• Study Completion Date: 2023-11-30

Brief Summary

The aims of this study are to:

1. Determine the proportion of participants who are underdosed or overdosed under recommended dosing regimen of escitalopram for the depression treatment (10 mg/day)

2. Determine and quantify clinical benefits of personalized escitalopram dosing regimen based on the escitalopram blood level monitoring

3. Retrospectively estimate whether the information on CYP2C19 genotype is useful in the prediction of escitalopram blood level.

Detailed Description

Escitalopram is an antidepressant extensively metabolized by the polymorphic CYP2C19 enzyme. Based on CYP2C19 genotype, patients can be classified either as:

• Normal metabolizers (Normal CYP2C19 enzyme capacity)
• Intermediate metabolizers (Decreased CYP2C19 enzyme capacity)
• Poor metabolizers (Absent CYP2C19 enzyme capacity)
• Ultra rapid metabolizers (Increased CYP2C19 enzyme capacity)

Adequate escitalopram exposure is needed to achieve optimal clinical response in the treatment of depression: too low drug plasma levels can lead to the lack of pharmacological effect, whereas too high drug plasma levels increases the incidence of adverse effects. There is evidence that patients with variant CYP2C19 genotypes have abnormal escitalopram exposure and could benefit from escitalopram dose personalization, but precise evidence-based protocol for personalized dosing of escitalopram has not been developed yet. This multicentric observational clinical trial is designed to collect crucial information for the development of such protocol that will be based on drug plasma level monitoring and/or CYP2C19 genotyping.

The course of the study will be as follows:

Initial Visit (V0):

Participant will be enrolled at this point if inclusion criteria are met. Escitalopram therapy will be initiated at the standard dose of 10 mg/day during next 2 weeks, or alternatively, started with 5 mg/day during first week and then increased to 10 mg/day during second week. General and socio-demographic information about the participant will be collected together with the baseline measurements: clinical questionnaires, anthropometric measurements, cardiology assessments, and the blood sample will be taken for biochemical analyses.

Mid-Visit (VK):

This visit takes place two weeks after the initial visit (V0) when escitalopram blood level is expected to reach the steady state. Blood sample will be taken from the participants at the end of the dose interval (before the morning dose) for the purpose of therapeutic drug monitoring. Plasma escitalopram levels will then be measured before the next visit and an independent clinician will allocate patients into one out of two cohorts based on whether or not escitalopram levels were optimal (25 - 50 ng/ml). If escitalopram levels were outside this interval, independent clinician will adjust the dose; escitalopram level lower than 5 ng/ml indicates noncompliance and results in dropout, level between 5 and 15 ng/ml results in dose increase to 20 mg/day, level between 15 and 25 ng/ml results in dose increase to 15 mg/day, level between 25 and 50 ng/ml results in treatment continuation with 10 mg/day, and level higher than 50 ng/ml results in dose decrease to 5 mg/day.

Visit 1 (V1):

Visit 1 takes place two weeks after VK and 4 weeks after the initiation of the escitalopram therapy. Without the knowledge of the attending clinician, independent clinician will adjust escitalopram doses accordingly. Attending clinician will then assess the participants using standardized questionnaires, participants will be anthropometrically and cardiologically examined, and blood samples will be taken for the purposes of therapeutic drug monitoring and biochemical analyses.

Visit 2 (V2):

Visit 2 is the final follow-up visit and it will be performed 4 weeks after the Visit 1 and 8 weeks after the escitalopram initiation. All participants will be assessed for psychometrical, anthropometrical and cardiological parameters, and blood samples will be taken again for the purposes of therapeutic drug monitoring and biochemical analysis.

If needed, additional participants, who are already on the stable escitalopram monotherapy, can be enrolled into study starting from VK. In this case, besides the blood sample for the therapeutic drug monitoring, all assessment usually done at initial visit (V0) will be performed during VK.

Conditions

Depressive Disorder, Major

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Standard dose

Patients are allocated to this group at visit V1 if 10 mg/day escitalopram treatment resulted in optimal escitalopram exposure (25-50 ng/ml) as measured at VK. These patients will continue their treatment with 10 mg/day during the V1-V2 period.

Escitalopram

Intervention Type: DRUG

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), is commercially known as ELORYQA®, Elicea®, Escital®,PRAMES® or Lata® in Serbia. The recommended dose for Major depressive disorder is 10mg/day. Based on the individual response, dose can be adjusted and the maximum dose is 20 mg/day; 5 mg/day dose is also available. Escitalopram is also indicated for treatment of Obsessive-compulsive disorder, Generalized anxiety disorder, Social anxiety disorder (Social phobia) and Panic disorder (with or without agoraphobia) by Medicines and Medical Devices Agency of Serbia.

In known CYP2C19 poor metabolizers, initial dose should be 5mg/day during first 2 weeks, and based on the individual response it can be increased up to maximum of 10 mg of escitalopram per day, according to the guidelines of Medicines and Medical Devices Agency of Serbia.

Adjusted dose

Patients are allocated to this group at visit V1 if 10 mg/day escitalopram dose resulted in to high (\>50 ng/ml) or to low (\<25 ng/ml) escitalopram exposure, as measured at VK. These patients will be treated with the adjusted escitalopram dose, different from 10 mg/day, during the V1-V2 period.

Escitalopram

Intervention Type: DRUG

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), is commercially known as ELORYQA®, Elicea®, Escital®,PRAMES® or Lata® in Serbia. The recommended dose for Major depressive disorder is 10mg/day. Based on the individual response, dose can be adjusted and the maximum dose is 20 mg/day; 5 mg/day dose is also available. Escitalopram is also indicated for treatment of Obsessive-compulsive disorder, Generalized anxiety disorder, Social anxiety disorder (Social phobia) and Panic disorder (with or without agoraphobia) by Medicines and Medical Devices Agency of Serbia.

In known CYP2C19 poor metabolizers, initial dose should be 5mg/day during first 2 weeks, and based on the individual response it can be increased up to maximum of 10 mg of escitalopram per day, according to the guidelines of Medicines and Medical Devices Agency of Serbia.

Interventions

Escitalopram

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), is commercially known as ELORYQA®, Elicea®, Escital®,PRAMES® or Lata® in Serbia. The recommended dose for Major depressive disorder is 10mg/day. Based on the individual response, dose can be adjusted and the maximum dose is 20 mg/day; 5 mg/day dose is also available. Escitalopram is also indicated for treatment of Obsessive-compulsive disorder, Generalized anxiety disorder, Social anxiety disorder (Social phobia) and Panic disorder (with or without agoraphobia) by Medicines and Medical Devices Agency of Serbia.

In known CYP2C19 poor metabolizers, initial dose should be 5mg/day during first 2 weeks, and based on the individual response it can be increased up to maximum of 10 mg of escitalopram per day, according to the guidelines of Medicines and Medical Devices Agency of Serbia.

Intervention Type: DRUG

Other Intervention Names

Lexapro; Citalex

Eligibility Criteria

Inclusion Criteria

• Diagnosed Major Depressive Disorder
• Starting monotherapy with escitalopram
• Signed written informed consent

Exclusion Criteria

• Patient's requests to leave the study
• Patients who had taken escitalopram before
• Dementia
• Severe liver function impairment (abnormal AST/ALT ratio)
• Severe kidney function impairment (abnormal creatinine clearance)
• History of drug addiction (sporadic use is permitted)
• Suicide risk
• Patients who are taking strong CYP2C19 inhibitors
• Severe adverse drug reaction

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Centre of Serbia

OTHER

Sponsor Role: collaborator

Institute of Mental Health, Serbia

UNKNOWN

Sponsor Role: collaborator

Military Medical Academy, Belgrade, Serbia

OTHER

Sponsor Role: collaborator

University of Belgrade

OTHER

Sponsor Role: lead

Responsible Party

Marin Jukic

Assistant Professor, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Clinical Centre of Serbia

Belgrade, , Serbia

Site Status: RECRUITING

Military Medical Academy

Belgrade, , Serbia

Site Status: NOT_YET_RECRUITING

Institute of Mental Health

Belgrade, , Serbia

Site Status: RECRUITING

Countries

Serbia

Central Contacts

Marin M Jukić, PhD

Role: CONTACT

marin.jukic@pharmacy.bg.ac.rs

+381 11 3951 314

Facility Contacts

Zorana Pavlović, M.D.

Role: primary

zorana.pavlovic@med.bg.ac.rs

+381 11 366 2093

Zvezdana Stojanović, M.D.

Role: primary

vma@mod.gov.rs

+381 11 3609386

Čedo Miljević, M.D.

Role: primary

cedo.miljevic@med.bg.ac.rs

+381 11 3307 500

References

Pennebaker JW, Susman JR. Disclosure of traumas and psychosomatic processes. Soc Sci Med. 1988;26(3):327-32. doi: 10.1016/0277-9536(88)90397-8.

Reference Type: BACKGROUND

PMID: 3279521 (View on PubMed)

Jukic MM, Haslemo T, Molden E, Ingelman-Sundberg M. Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients. Am J Psychiatry. 2018 May 1;175(5):463-470. doi: 10.1176/appi.ajp.2017.17050550. Epub 2018 Jan 12.

Reference Type: BACKGROUND

PMID: 29325448 (View on PubMed)

Milosavljevic F, Bukvic N, Pavlovic Z, Miljevic C, Pesic V, Molden E, Ingelman-Sundberg M, Leucht S, Jukic MM. Association of CYP2C19 and CYP2D6 Poor and Intermediate Metabolizer Status With Antidepressant and Antipsychotic Exposure: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Mar 1;78(3):270-280. doi: 10.1001/jamapsychiatry.2020.3643.

Reference Type: BACKGROUND

PMID: 33237321 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

6066800-E

Identifier Type: -

Identifier Source: org_study_id