Depression is common after acute coronary syndrome (ACS), adversely affecting cardiac course and prognosis. There have been only a few evidence-based treatment options for depression in ACS. Accordingly, we planned the Korean Depression in ACS (K-DEPACS) study, which investigated depressive disorders in patients with ACS using a naturalistic prospective design, and the Escitalopram for DEPACS (EsDEPACS) trial, which assessed the efficacy and safety of escitalopram for treating major or minor depression in patients with ACS. Participants in the K-DEPACS study were consecutively recruited from patients with ACS who were recently hospitalized at Chonnam National University Hospital, Gwangju, South Korea. Diagnoses were confirmed by coronary angiography from 2005. Data on depressive and cardiovascular characteristics were obtained at 2 weeks, 3 months, 12 months, and every 6 months thereafter following the index ACS admission. The K-DEPACS participants who met the DSM-IV criteria for major or minor depressive disorder were randomly assigned to groups in the 24-week, double-blind, placebo-controlled EsDEPACS trial beginning in 2007. The outcome of treatments for depressive and other psychiatric symptoms, issues related to safety, including general adversity, and cardiovascular factors were assessed. The K-DEPACS study can significantly contribute to research on the complex relationships between depression and ACS. The results of the EsDEPACS trial provide an additional treatment option for clinicians treating these patients.
Depression is common in acute coronary syndrome [ACS; including myocardial infarction (MI) or unstable angina (UA)]. The prevalence of major depression was estimated to range from 15% to 27%.
A number of randomized controlled trials, mostly with selective serotonin reuptake inhibitors (SSRIs), have examined the impact of pharmacological interventions on depression in patients with ACS. However, the trials conducted addressing this theory have produced mixed results. Fluoxetine was shown to be effective and safe for treating patients with post-MI depression.
First, previous clinical trials have focused primarily on major depressive disorders.
We designed the Korean Depression in Acute Coronary Syndrome (K-DEPACS) to complement previous studies. The present study investigated depressive disorders in patients with ACS using a naturalistic prospective design. Patients with a diagnosis of a major or minor depressive disorder were enrolled in a 24-week, double-blind, placebo-controlled trial to assess the efficacy and safety of Escitalopram for Depression in ACS (EsDEPACS). The trial is registered at www.clinicaltrials.gov, registry number: NCT00419471. Escitalopram was chosen because of its antiplatelet effects in depressed patients,
The K-DEPACS study investigated the occurrence, risk factors, and longitudinal course of psychological disorders (depression in particular) in survivors of recently developed ACS as well as the effects of depression on cardiac course and prognosis. The EsDEPACS study evaluated the efficacy and safety of escitalopram in the treatment of depressed patients with ACS and determined the effects of escitalopram on other psychiatric outcomes, including social functioning, disability, and quality of life.
The outlines of the K-DEPACS and EsDEPACS studies are presented in
All patients who visited the study site with angina symptoms and were hospitalized were approached for enrollment in the K-DEPACS study at 2 week after the index ACS. Patients who met the depression criteria in that hospitalized setting or at an outpatient setting, every 1 month thereafter up to 3 months were qualified for inclusion in the EsDEPACS study. Inclusion and exclusion criteria for both studies are summarized in
General information on socio-demographic characteristics and health status were obtained. Cardiovascular medications were recorded. Measurements of depressive symptoms included the 17-item Hamilton Depression Rating Scale (HAMD),
The efficacy and safety of flexible doses of escitalopram (5 mg, 10 mg, 15 mg, or 20 mg) were investigated using a double-blind, placebo-controlled design. The escitalopram and placebo were provided by H. Lundbeck A/S (Copenhagen, Denmark). Patients were randomized in a 1 : 1 ratio for assignment into the ecsitalopram or placebo group according to computer-generated randomization codes. Patient visits were scheduled at baseline and at 4, 8, 12, 16, 20, and 24 weeks (±7-day visit window was allowed) thereafter. Patients received one tablet of escitalopram 5 mg, 10 mg, or 20 mg or two tablets of escitalopram (5 mg plus 10 mg) for a 15-mg dose per day or a matched placebo. The initial dose at baseline evaluation was typically 10 mg/day, but subjects aged 65 years or over and those with hepatic dysfunction received 5 mg/day. After the second evaluation (week 4), the medication doses could be changed and were determined by the investigators' clinical judgment based on the response to and tolerability of treatment. Medications were taken orally once daily within 30 min after supper. Adherence to the medication regimen was confirmed by pill counts at every visit and was defined as acceptable when at least 75% of the medication was taken. At the end of 24 weeks of double-blind treatment, the study was completed, and study medication was tapered. To ensure patient safety, follow-up treatment was provided at the outpatient clinic of the psychiatric department when the clinician determined a need for further treatment. Concomitant medications, such as any other antidepressants, psychostimulants, antipsychotics, and anticholinergics, were not permitted. However, transient use of analgesics, antipyretics, and cold medicines, as well as hypnotics such as zolpidem, triazolam, and benzodiazepines, was allowed.
The primary efficacy outcome measure was the HAMD. The secondary depression outcome measures were the MADRS, BDI, and CGI-s. Other psychiatric outcome measures included the SOFAS, WHODAS-12, WHOQOL-BREF, and Chonnam National University Hospital-Leeds Sleep Evaluation Questionnaire (CNUH-LSEQ).
The overall sample size was estimated from the number of subjects needed for the EsDEPACS trial. The ESDEPACS trial was designed to produce 80% power to detect small to medium effect sizes (0.35) on the primary efficacy outcome for both treatments (i.e., a mean score difference of 2 on the HAMD assuming a SD of 5-6) in the ITT analyses for all randomized participants when performing two-sided tests at α=0.05. These assumptions yielded a sample size of 106 patients per group. As a previous study reported that a considerable proportion of Korean patients who were depressed (30%) discontinued the study after the baseline evaluation,
The K-DEPACS study is a meaningful and significant contribution to the research on the complex relationships between depression and ACS. The particular prospective naturalistic study design might facilitate other related studies and enhance the understanding on this issue.
This research was supported by a grant of the Korea Health 21 R&D, Ministry of Health and Welfare, Republic of Korea (HI10C2020) and an unrestricted research grant from H. Lundbeck A/S. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Flow chart of the K-DEPACS and EsDEPACS studies. BDI: Beck Depression Inventory, ACS: acute coronary syndrome, K-DEPACS: Korean Depression in Acute Coronary Syndrome study, MINI: Mini-International Neuropsychiatric Interview, EsDEPACS: Escitalopram for Depression in Acute Coronary Syndrome.
Selection criteria
K-DEPACS: Korean Depression in Acute Coronary Syndrome study, EsDEPACS: Escitalopram for Depression in Acute Coronary Syndrome, ACS: acute coronary syndrome, MI: myocardial infarction, UA: unstable angina, BDI: Beck Depression Inventory, DSM-IV: Diagnostic and Statistical Manual, 4th edition, MINI: Mini-International Neuropsychiatric Interview, BP: blood pressure