Correlates and Escitalopram Treatment Effects on Sleep Disturbance in Patients with Acute Coronary Syndrome: K-DEPACS and EsDEPACS.
ABSTRACT: To investigate the correlates of sleep disturbance and to assess escitalopram treatment effects of depression on sleep disturbance in patients with acute coronary syndrome (ACS).A cross-sectional study in patients with ACS within 2 w post-ACS, and a 24-w double-blind controlled trial of escitalopram against placebo for patients with ACS who have comorbid depressive disorders.A university hospital in South Korea.There were 1,152 patients with ACS who were consecutively recruited. Of 446 patients with comorbid depressive disorders, 300 were randomized to the trial.Sleep disturbance was evaluated by the Leeds Sleep Evaluation Questionnaire. Demographic and clinical characteristics were assessed, including cardiovascular risk factors, current cardiac status, and depressive symptoms. Depressive symptoms were most strongly and consistently associated with sleep disturbance. In addition, older age, female sex, hypertension, and more severe ACS status were associated with certain aspects of sleep disturbance. Escitalopram was significantly superior to placebo for improving sleep disturbance over the 24-w treatment period. These effects were substantially explained by improvement in depressive symptoms.Depression screening is indicated in patients with acute coronary syndrome with sleep disturbance. Successful treatment of depression has beneficial effects on sleep outcomes in these patients.ClinicalTrial.gov identifier for the 24-w drug trial, NCT00419471.
Project description:This study aimed to investigate the effect of statins for the treatment of depression in individuals with acute coronary syndrome (ACS). We used 1-year follow-up data of a 24-week double-blind, placebo-controlled trial of escitalopram and a naturalistic prospective observational cohort study. Of 446 participants with comorbid depressive disorders and ACS at baseline, 300 participated in a randomised escitalopram trial and the remaining 146 participated in a naturalistic observational study. The participants in the two studies were approached for a 1-year follow-up investigation. Treatment response rates, defined as a ? 50% reduction in the Hamilton Depression Rating Scale (HAM-D) and Beck Depression Inventory (BDI) scores, were used as the outcome variables. In the escitalopram trial, both HAM-D and BDI response rates were highest in patients taking escitalopram and statins together and lowest in patients receiving neither medication. Logistic regression analyses revealed that statin use was significantly associated with higher response rates on both the HAM-D and BDI at 1 year, whereas no such associations were found for escitalopram. In the naturalistic observational study, the response rates at 1 year did not differ significantly by statin use. Instead, the HAM-D response rate was significantly higher in patients taking lipophilic statins than in those who did not. In conclusion, statins may be effective for the treatment of depression independent of medical status and escitalopram use, and they may potentiate the antidepressant action of serotonergic antidepressants in patients with ACS.
Project description:Objective:There are no evidence-based practices for treating anxiety in patients with acute coronary syndrome (ACS). Thus, we investigated the effects of escitalopram on anxiety in this population. Methods:We enrolled 217 patients with ACS who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for depressive disorders into a randomized double-blind placebo-controlled study. Patients received either escitalopram or placebo over a 24-week period. Anxiety symptoms were evaluated using the Hospital Anxiety and Depression Scale-anxiety subscale (HADS-A). A HADS-A score >7 was classified as an anxiety disorder. Baseline evaluations included sociodemographic and clinical characteristics, such as depressive symptoms, cardiovascular risk factors, and current cardiac status. Results:Independent of improvements in depression and without any differences in safety profiles, escitalopram treatment was significantly more efficacious in treating and reducing anxiety than placebo over a 24-week period. Conclusion:Escitalopram can be recommended as an effective and safe treatment option for anxiety in patients with ACS.
Project description:Genes related to serotonin are associated with responses to treatment for depression. We examined associations between the serotonin transporter (5-HTT) and serotonin 2a receptor (5-HTR2a) genes and responses to treatment for depressive disorders in acute coronary syndrome (ACS). A total of 255 patients who met the DSM-IV major or minor depressive disorder and recently developed ACS were randomly assigned to the escitalopram (n=127) or placebo (n=128) group in this 24-week double-blind trial (ClinicalTrial.gov identifier: NCT00419471). Remission was defined as a Hamilton Rating Scale for Depression (HAMD) score ?7. Assays were performed for the 5-HTTLPR, STin2 VNTR, 5-HTR2a 102T/C, and 5-HTR2a 1438A/G genotypes. Escitalopram was superior to placebo for treating depressive disorder with ACS but there were no significant associations between serotonergic genes and treatment responses even when considering ACS severity. The effect of escitalopram was independent of 5-HTT and 5-HTR2a polymorphisms.
Project description: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.
Project description:OBJECTIVE:The role of obsessive-compulsive symptoms (OCS) in patients with acute coronary syndrome (ACS) is not well elucidated. This study investigated the association between OCS and the long-term prognosis of ACS in tandem with depression comorbidity and treatment. METHODS:A cross-sectional baseline study and a nested 24-week double-blind escitalopram-placebo controlled trial were carried out between May 2007 and March 2013, and then a 5-12-year follow-up for major adverse cardiac events (MACE) was conducted. A total of 1,152 patients with ACS were stratified by baseline depression comorbidity and treatment allocation into four groups: no depression (706 patients), depression and taking escitalopram (149 patients), depression and taking a placebo (151 patients), and depression and receiving medical care as usual (CAU; 146 patients). OCS were evaluated using the Symptom Checklist-90-Revised Obsessive-Compulsive symptom domain. During the follow-up, Kaplan-Meier event rates for MACE outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates. RESULTS:A higher OCS score at baseline was associated with a worse ACS prognosis after adjusting for relevant covariates and across MACE outcomes. This association varied according to the depression comorbidity. The association was significant in patients without depression and depressive patients receiving placebos and CAU, but not in depressive patients on escitalopram. CONCLUSION:Evaluating OCS and depression is recommended during the early phase of ACS. Treatment for OCS may improve the longterm cardiac outcomes of patients with ACS.
Project description:We investigated roles of plasma homocysteine and MTHFR gene in relation to risks and treatment responses of depression in ACS. A sample of 969 patients with recent ACS were recruited and 711 followed 1 year later. In addition, of 378 baseline participants with depressive disorder, 255 were randomized to a 24-week double blind trial of escitalopram (N = 127) or placebo (N = 128). A higher homocysteine concentration was independently associated with prevalent depressive disorder at baseline irrespective of MTHFR genotype; and with both incident and persistent depressive disorder at follow-up only in the presence of TT genotype. MTHFR genotype was not itself associated with depressive disorder after ACS. No associations were found with 24-week antidepressant treatment responses. Plasma homocysteine could be a biomarker for depressive disorder particularly in the acute phase of ACS. Focused interventions for those with higher homocysteine level and MTHFR TT genotype might reduce the risk of later depressive disorder.
Project description:Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS."The effect of MElatonin and Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms.Previously, only selective serotonin reuptake inhibitors (SSRIs) have been investigated in a primary preventive setup in patients following ACS. However, SSRIs are associated with several side effects. An ideal intervention would constitute the highest degree of prevention of depressive symptoms with the lowest risk of side effects. In this regard, melatonin may have advantages due to its low toxicity as well as its proven anxiolytic and hypnotic effects.ClinicalTrials.gov, Identifier: NCT02451293 . Registered on 12 May 2015. EudraCT nr. 2015-002116-32.
Project description:Importance:Depression has been associated with poorer medical outcomes in acute coronary syndrome (ACS), but there are few data on the effects of antidepressant treatment on long-term prognosis. Objective:To investigate the effect on long-term major adverse cardiac events (MACE) of escitalopram treatment of depression in patients with recent ACS. Design, Setting, and Participants:Randomized, double-blind, placebo-controlled trial conducted among 300 patients with recent ACS and depression enrolled from May 2007 to March 2013, with follow-up completed in June 2017, at Chonnam National University Hospital, Gwangju, South Korea. Interventions:Patients were randomly assigned to receive either escitalopram in flexible dosages of 5, 10, 15, or 20 mg/d (n?=?149) or matched placebo (n?=?151) for 24 weeks. Main Outcomes and Measures:The primary outcome was MACE, a composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI). Four secondary outcomes were the individual MACE components of all-cause mortality, cardiac death, MI, and PCI. Cox proportional hazards models were used to compare the escitalopram and placebo groups by time to first MACE. Results:Among 300 randomized patients (mean age, 60 years; 119 women [39.3%]), 100% completed a median of 8.1 (interquartile range, 7.5-9.0) years of follow-up. MACE occurred in 61 patients (40.9%) receiving escitalopram and in 81 (53.6%) receiving placebo (hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P?=?.03). Comparing individual MACE outcomes between the escitalopram and placebo groups, respectively, incidences for all-cause mortality were 20.8% vs 24.5% (HR, 0.82; 95% CI, 0.51-1.33; P?=?.43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% CI, 0.41-1.52; P?=?.48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% CI, 0.27-0.96; P?=?.04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% CI, 0.33-1.04; P?=?.07). Conclusions and Relevance:Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings. Trial Registration:ClinicalTrials.gov Identifier: NCT00419471.
Project description:Alcohol dependence comorbid with major depressive disorder poses a major challenge in the clinical setting. The results in the treatment with selective serotonin re-uptake inhibitors have been conflicting. Thus, we compared in alcohol-dependent patients with co-morbid major depressive disorder the selective serotonin re-uptake inhibitor escitalopram to a compound that acts on different transporter system and may reduce craving, the glutamate receptor antagonist memantine.Eighty alcohol-dependent patients comorbid with major depressive disorder in municipal alcohol clinics were randomized 1:1 to receive memantine 20 mg or escitalopram 20 mg in a double-blind manner. During the 26-week study period patients continued their routine treatment at the clinics. Abstinence was not required but encouraged. The patients attended visits weekly during the first month, and then at 3 and at 6 months. Outcome measures were Alcohol Use Disorders Identification Test (AUDIT), Obsessive Compulsive Drinking Scale (OCDS) and Drinking Diary.The completion rate was high in both groups, especially among the patients who had been abstinent at the beginning of the study. However, among those patients who were not abstinent at baseline, 47% in both groups discontinued the study. Numbers of abstinent days were high in both groups throughout the study. Alcohol consumption measured by the AUDIT QF (quantity-frequency) score was significantly reduced in both groups, as was the craving for alcohol measured by the OCDS. Early age at first alcohol intoxication predicted poor treatment outcomes in patients treated with escitalopram, and the same was seen with the early onset of the first depressive episode. The same predictive effects were not found in patients treated with memantine.Our results indicate that both memantine and escitalopram are useful adjunct medications for the treatment of alcohol dependence co-morbid with major depression. Memantine was at least as effective with regard to drinking as escitalopram. We believe that a direct comparison of memantine, with the commonly used escitalopram, can provide useful information for clinicians on the treatment of alcohol dependency co-morbid with MDD.
Project description:Sleep disturbance is frequently comorbid with depression and sleep complaints are the most common residual symptoms after treatment among adolescents with depression. The present analyses investigated the effect of sleep disturbance in depressed adolescents treated with Interpersonal Psychotherapy for Adolescents (IPT-A) versus Treatment as Usual (TAU) in school-based mental health clinics.63 adolescents participated in a randomized clinical trial of IPT-A versus TAU for adolescent depression. Participants were diagnosed with a DSM-IV depressive disorder and assessed for symptoms of depression, interpersonal functioning and sleep disturbance. Measures were assessed at baseline, session 4 and 8 of treatment, and session 12 for post-acute treatment follow-up. Hierarchical linear modeling (HLM) was used to model change in depression, interpersonal functioning and sleep disturbance.Ongoing sleep disturbance was significantly associated with worse depression scores as rated by clinician (? = 1.04, SE = 0.22, p < .001) and self-report (? = 1.63, SE = 0.29, p < .001), as well as worse interpersonal functioning across the course of treatment (? = 0.09, SE = 0.02, p < .001). Treatment condition did not predict change in sleep disturbance (? = -0.13, SE = 0.14, p = ns).For all patients in the study, sleep disturbance was a predictor of depression and interpersonal functioning for depressed adolescents. Sleep disturbance predicted more depression and interpersonal stress across treatments and led to a slower improvement in depression and interpersonal functioning. This data suggests that sleep disturbance should be a target for future treatment development research among depressed adolescents.