Non-interventional, Retrospective Cohort Study to Explore Antidepressant Treatment in Korea

Comparison of Antidepressants in the Real-World: Retrospective Cohort Study Using Big Data

The primary purpose of this study is to investigate medication utilization pattern and risk of adverse outcomes among commonly used antidepressants by using nationwide claims database, in order to assess overall clinical benefit of antidepressant therapy in real-world practice.

Study Overview

• Status: Completed
• Conditions: Major Depression
• Intervention / Treatment: Drug: Escitalopram; Drug: Paroxetine; Drug: Fluoxetine; Drug: Mirtazapine; Drug: Duloxetine; Drug: Sertraline; Drug: Venlafaxine; Drug: Tianeptine; Drug: Vortioxetine; Drug: Desvenlafaxine; Drug: Bupropion

Detailed Description

While there are many antidepressants from which physicians can select based on efficacy and tolerability profile, evidence on effectiveness and safety outcomes of new antidepressants in real clinical practice among Korean MDD population is limited.

Hence, this study will explore the following primary, secondary objectives using national health insurance database :

1. Explore baseline characteristics and drug utilization patterns of 11 commonly used antidepressant therapy during 90 days of acute treatment phase
2. Explore drug utilization patterns such as therapy changes, medication compliance and recurrence relationship, and risk of adverse outcomes during maintenance phase
3. Choice of antidepressants and drug utilization patterns in patients with various comorbidities
4. The relationship of non-pharmacologic treatment and discontinuation, medication compliance
5. Choice of antidepressants by non-psychiatric specialty

• Study Type: Observational
• Enrollment (Actual): 370212

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Pfizer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Subjects who newly initiated antidepressant therapies between Jan 01, 2017 to Jun 30, 2018 in the National Health Insurance Service (NHIS) database

Description

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for inclusion in the study:

1. Patients aged 18 years or older on the index date
2. Patients who had at least one inpatient claim or two outpatient claims in the intake period with any of the following diagnosis codes F06.3 Organic mood [affective] disorders F32* Depressive episode F33* Recurrent depressive disorder F34.1 Neurotic depression F38.1 Other recurrent mood [affective] disorder F41.2 Mixed anxiety and depressive disorder
3. Patients prescribed any of the following antidepressant during intake period (from January 1, 2017 to June 30, 2018)

Exclusion Criteria

Patients meeting any of the following criteria will not be included in the study:

1. Patients with a claim of diagnosis codes in Table 1 during the 12 month pre-index period
2. Patients with a claim of prescription in Table 2 during the 12 month pre-index period
3. Patient who had a claim as a beneficiary of Medical Aid program (Korean Medicaid program with free or minimum copay)
4. Patients who are hospitalized at the index date
5. Patients who are under hospice care (procedure codes WG*-WO*)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

11

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1. Escitalopram Cohort	Drug: Escitalopram; Treatment for depression
2. Paroxetine Cohort	Drug: Paroxetine; Treatment for depression
3. Fluoxetine Cohort	Drug: Fluoxetine; Treatment for depression
4. Mirtazapine Cohort	Drug: Mirtazapine; Treatment for depression
5. Duloxetine Cohort	Drug: Duloxetine; Treatment for depression
6. Sertraline Cohort	Drug: Sertraline; Treatment for depression
7. Venlafaxine Cohort	Drug: Venlafaxine; Treatment for depression
8. Tianeptine Cohort	Drug: Tianeptine; Treatment for depression
9. Vortioxetine Cohort	Drug: Vortioxetine; Treatment for depression
10. Desvenlafaxine Cohort	Drug: Desvenlafaxine; Treatment for depression
11. Bupropion Cohort	Drug: Bupropion; Treatment for depression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication Possession Ratio (MPR) During First 180 Days of Treatment	MPR= Days of medication possession from the prescriptions filled in the 180 days divided by (180 days plus + extra days of drug supply from the last prescription fill during the 180 days). MPR by each index drug including escitalopram, paroxetine, fluoxetine, mirtazapine, duloxetine, sertraline, venlafaxine, tianeptine, vortioxetine, desvenlafaxine and bupropion is reported in this outcome measure. Index date was first prescription date of study drugs during intake period.	From index date (anytime between 01-Jan-2018 to 31-Dec-2019) up to 180 days of treatment (data collected and observed retrospectively)
Persistence During First 180 Days of Treatment	Persistence was defined as the average length of treatment on the index drugs (escitalopram, paroxetine, fluoxetine, mirtazapine, duloxetine, sertraline, venlafaxine, tianeptine, vortioxetine, desvenlafaxine and bupropion), allowing 14-day permissible gap. Index date was first prescription date of study drugs during intake period.	From index date (anytime between 01-Jan-2018 to 31-Dec-2019) up to 180 days of treatment (data collected and observed retrospectively)
Percentage of Participants Who Discontinued Treatment in the First 90 Days From the Index Date	Percentage of participants who discontinued the treatment in first 90 days from the index date is reported in this outcome measure. Index date was the first prescription date of study treatment during the intake period.	From the index date (anytime between 01-Jan-2018 to 30-Jun-2019) up to 90 days of treatment (data collected and observed retrospectively)
Percentage of Participants Who Adhered to Treatment Measured by MPR (More Than or Equal to [>=] 75 Percent [%])	Adherence was defined when MPR >= 75%. MPR = (Days of medication possession from the prescriptions filled in the 180 days) / (180 days + extra days of drug supply from the last prescription fill during the 180 days. Index date was the first prescription date of study drugs during the intake period.	From the index date (anytime between 01-Jan-2018 to 30-Jun-2019) up to 180 days of treatment (data collected and observed retrospectively)
Percentage of Participants Experiencing Recurrence During the Acute Treatment Phase	Recurrence during the acute treatment phase was defined as either one of the following: 1) Inpatient episode with a diagnosis code. 2) Inpatient episodes via the department of psychiatry or emergency medicine. 3) Inpatient episode via nursing hospital. 4) Emergency room visit with a diagnosis code. 5) Suicide attempt. Acute phase considered as the first 90-day period starting from the index date. Index date was the first prescription date of study treatment during the intake period. Diagnosis codes used for inclusion were: F06.3-Organic mood(affective) disorders, F32*- Depressive episode, F33*- Recurrent depressive disorder, F34.1- Neurotic depression, F38.1- Other recurrent mood(affective) disorders, F41.2- Mixed anxiety and depressive disorder.	From the index date (anytime between 01-Jan-2018 to 30-Jun-2019) up to 90 days of treatment (data collected and observed retrospectively)
Percentage of Participants Experiencing Recurrence After the Acute Treatment Phase	Recurrence was defined as either one of the following: 1) Inpatient episode with a diagnosis code. 2) Inpatient episodes via the department of psychiatry or emergency medicine. 3) Inpatient episode via nursing hospital. 4) Emergency room visit with a diagnosis code. 5) Suicide attempt; antidepressant prescription after 30 days of drug holiday. Acute phase considered as the first 90-day period starting from the index date. Index date was the first prescription date of study treatment during the intake period.	From day 91 to day 180 from the index date (anytime between 01-Jan-2018 to 30-Jun-2019) (data collected and observed retrospectively)
Percentage of Participants With Adverse Events (AE) Within Maintenance Phase of Treatment	An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. Maintenance phase was during the second 90-day period (91 to 180 days) starting from the index date. Index date was the first prescription date of study treatment during the intake period. Index date was the first prescription date of study treatment during the intake period.	From 91 up to 180 days of treatment from index date (anytime between 01-Jan-2018 to 30-Jun-2019) (data collected and observed retrospectively)
Percentage of Prescriptions for Commonly Used Antidepressants in Acute Treatment Phase	Percentage of prescriptions for commonly used antidepressants in acute treatment phase were assessed. Acute treatment phase was during the first 90-day period starting from the index date. Index date was the first prescription date of study treatment during the intake period.	From the index date (anytime between 01-Jan-2018 to 30-Jun-2019) up to 90 days of treatment (data collected and observed retrospectively)
Average Daily Dosage at Index Date	Index date was the first prescription date of study treatment during the intake period.	At index date (anytime between 01-Jan-2018 to 30-Jun-2019) (data collected and observed retrospectively)
Average Daily Dosage During the Acute Treatment Phase	Acute treatment phase was during the first 90-day period starting from the index date.	From the index date (anytime between 01-Jan-2018 to 30-Jun-2019) up to 90 days of treatment (data collected and observed retrospectively)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug utilization pattern in acute phase	Percentage of patients on monotherapy, combination therapy, augmentation therapy during 90 days of treatment	90 days
Drug utilization pattern in maintenance phase	Precentage of patients on monotherapy, combination therapy, augmentation therapy during 90-180 days of treatment	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants on Monotherapy, Combination Therapy, Augmentation Therapy During Acute Treatment Phase	Percentage of participants who received monotherapy, combination therapy and augmentation therapy during 90 days of treatment were assessed in this outcome measure. Acute treatment phase was during initial 90 days from the index date.	From the index date (anytime between 01-Jan-2018 to 30-Jun-2019) up to 90 days of treatment (data collected and observed retrospectively)
Drug Utilization Pattern of Participants During 90-180 Days of Treatment	The drug utilization pattern is presented according to the average treatment duration for each antidepressant during the maintenance treatment phases.	From 90 days to 180 days of treatment (data collected and observed retrospectively)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2022
• Primary Completion (Actual): November 3, 2022
• Study Completion (Actual): November 3, 2022

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 9, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Serotonin and Noradrenaline Reuptake Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Central Nervous System Depressants; Sensory System Agents; Analgesics; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Membrane Transport Modulators; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Adrenergic Agents; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Adrenergic Antagonists; Serotonin 5-HT2 Receptor Antagonists; Adrenergic alpha-Antagonists; Histamine H1 Antagonists; Serotonin Receptor Agonists; Serotonin 5-HT1 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Antidepressive Agents, Tricyclic; Duloxetine Hydrochloride; Vortioxetine; Desvenlafaxine Succinate; Venlafaxine Hydrochloride; Mirtazapine; Escitalopram; Fluoxetine; Bupropion; Paroxetine; Sertraline; Tianeptine
• Other Study ID Numbers: B2061147; CAR-BIG Study (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes