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Biomedical subjects

Alexander H Glassman

Publications and source records attributed to Alexander H Glassman.

17 recordsLinked to original sources
PubMed2006

Onset of major depression associated with acute coronary syndromes: relationship of onset, major depressive disorder history, and episode severity to sertraline benefit.

CONTEXT: Depression observed following acute coronary syndrome (ACS) is common and associated with an increased risk of death. The Sertraline Antidepressant Heart Attack Trial (SADHART) tested the safety and efficacy of a selective serotonin reuptake inhibitor in this population. No evidence of harm was seen, and sertraline hydrochloride had an overall beneficial effect on mood that occurred primarily in patients with a history of episodes of major depressive disorder (MDD). OBJECTIVES: To determine how frequently the MDD began before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline. DESIGN, SETTINGS, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled treatment of 369 patients with ACS and MDD was conducted in 40 outpatient clinics in 10 countries between April 1, 1997, and April 30, 2001. MAIN OUTCOME MEASURES: Diagnosis of MDD, number of previous episodes of depression, and episode onset before or after hospitalization were established using the Diagnostic Interview Schedule. Treatment response was measured with the Clinical Global Impression-Improvement scale. RESULTS: Fifty-three percent of MDD episodes began before hospitalization for the index episode of ACS (for 197 of 369 patients), and 94% of the MDD episodes began more than 30 days before the index ACS episode. Episodes of MDD that began prior to ACS responded more frequently to sertraline than to placebo (63% vs 46%, respectively; odds ratio, 2.0; 95% confidence interval, 1.13-3.55) whereas depression with onset beginning after hospitalization showed a high placebo response rate (69% vs 60%, respectively) and low sertraline-placebo response ratio (1.15). Multivariate analysis indicated that time of onset of the current episode, history of MDD, and baseline severity independently predicted the sertraline-placebo response ratio. CONCLUSIONS: Half of the episodes of major depression associated with ACS began long before ACS and therefore were not caused by ACS. Patients whose current episodes of MDD begin before ACS, those with a history of MDD, and those whose episodes are severe should be treated because they will benefit considerably from sertraline. Since these 3 predictors of sertraline response are independent, having more than 1 of them substantially increases the benefit of sertraline while reducing the chance of spontaneous recovery.

Acute Disease↗
PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression.

OBJECTIVE: In a platelet/endothelial biomarker substudy of the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART), the authors sought to determine whether plasma levels of sertraline and its primary metabolite N-desmethylsertraline affect the release of platelet/endothelial biomarkers. METHOD: Fifty-five acute coronary syndrome patients with depression were randomly assigned to receive sertraline (N=23) or placebo (N=32). Twenty-six serial plasma samples collected at week 6 (N=12) and week 16 (N=14) were analyzed. Platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B(2) (TxB(2)), prostacyclin (6-keto-PGF1alpha), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured by enzyme-linked immunosorbent assay. Concentrations of sertraline and N-desmethylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples. RESULTS: Strong, mostly time-dependent negative correlations were found for the plasma levels of sertraline and N-desmethylsertraline with PF4 (week 6: r=-0.69 and -0.33, respectively; week 16: r=-0.63 for both), beta-TG (week 6: r=-0.43 and -0.29; week 16: r=-0.66 and -0.57), PECAM-1 (week 6: r=-0.82 and -0.49; week 16: r=-0.60 for both), P-selectin (week 6: r=-0.82 and -0.49; week 16: r=-0.73 and -0.43), and TxB(2) (week 6: r=-0.66 and -0.59; and week 16: r=-0.64 and -0.41). Regression analysis revealed some borderline correlations for endothelial markers such as 6-keto- PGF1alpha and E-selectin and a positive correlation for VCAM-1. CONCLUSIONS: This is the first documented evidence that plasma release of platelet/endothelial biomarkers is directly related to the levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. The clinical significance of these findings should be assessed in the setting of a randomized clinical trial.

Biomarkers↗
PubMed2005

Pharmacoeconomic analysis of sertraline treatment of depression in patients with unstable angina or a recent myocardial infarction.

BACKGROUND: The prevalence of major depressive disorder in patients with acute coronary syndromes (ACSs) is high and associated with worse cardiovascular outcomes and higher health care costs. Sertraline is the only treatment for major depressive disorder studied in a placebo-controlled trial of patients with ACS and found to be safe and effective. The cost implications of providing antidepressant treatment in this population have not yet been examined. The objective was to evaluate from a payer perspective the potential reduction in costs and psychiatric and cardiovascular events and procedures following sertraline versus placebo treatment of major depressive disorder in patients hospitalized for ACS. METHOD: Data were analyzed from a randomized, double-blind, placebo-controlled 24-week trial (Sertraline Antidepressant Heart Attack Randomized Trial) of sertraline treatment for major depressive disorder in patients hospitalized for ACS. Main outcome measures included frequency and costs (derived from Medicare diagnosis-related group fee schedules) of psychiatric and cardiovascular events occurring during the treatment period. RESULTS: There was a trend toward significantly fewer psychiatric or cardiovascular hospitalizations in the sertraline compared with the placebo group (55/186 vs. 76/183; p = .054). The mean per patient cost associated with psychiatric and medical events over the course of treatment was 2733 US dollars for sertraline and 3326 US dollars for placebo, but the difference was not statistically significant (p = .32). After including the costs of the sertra-line (360 US dollars over 24 weeks), there was no increase in treatment costs for sertraline compared with placebo. CONCLUSION: Sertraline treatment of major depressive disorder following hospitalization for a recent myocardial infarction or unstable angina appears to be a cost-effective strategy.

Angina, Unstable↗
PubMed2005

Schizophrenia, antipsychotic drugs, and cardiovascular disease.

Since the early 1980s, concern within the psychiatric community about whether antipsychotics are associated with adverse cardiovascular events has grown. In the early 1990s, it became clear that mesoridazine could cause torsades de pointes. More recently, concern has focused on the propensity that some atypical antipsychotics have to prolong corrected QT (QTc) interval and whether this can result in torsades de pointes and sudden death. Unfortunately, it has been difficult to accurately determine what role, if any, that atypical antipsychotics may have in contributing to these events, in part because of the rarity of the events and the lack of a sound, predictable marker. The best currently available markers, QTc interval and binding to the rapid delayed rectifier potassium current, are imprecise and cannot be relied upon to accurately predict torsades de pointes. Current evidence suggests that although atypical antipsychotics may increase the QTc interval, prolongation does not result in torsades de pointes, as observed with many conventional antipsychotics. Among the marketed atypical drugs, there was considerable concern about QTc prolongation with ziprasidone, but currently available data do not support the occurrence of torsades de pointes with any of the available atypical antipsychotic drugs. However, identifying when QTc prolongation carries a risk of torsades de pointes remains a problem in developing new drugs. Psychiatric populations are at high risk for cardiovascular disease, and emerging data indicate that some atypical antipsychotics may be associated with cardiovascular adverse events unrelated to QT prolongation. Thus, it is prudent for the psychiatric community to be aware of psychiatric patients' baseline medical condition and their risk status for cardiovascular disease.

Antipsychotic Agents↗
PubMed2003

Influence of depression and effect of treatment with sertraline on quality of life after hospitalization for acute coronary syndrome.

Major depressive disorders complicate recovery from acute coronary syndrome in approximately 1 in 5 patients, and have been found to be associated with significant impairments of quality of life and functioning. The aim of the present analysis was to evaluate the efficacy of sertraline in improving quality of life and functioning in patients diagnosed with major depression who had recently been hospitalized for acute coronary syndrome. Three hundred sixty-nine patients hospitalized in the previous month for acute coronary syndrome (myocardial infarction, 74%; unstable angina, 26%) who also met criteria for major depressive disorder were randomized to 24 weeks of double-blind treatment with sertraline (50 to 200 mg/day) or placebo. Quality-of-life and functional status were assessed using the Quality of Life, Enjoyment, and Satisfaction scale (Q-LES-Q) and the Medical Outcomes Study SF-36. Data from the total sample, and the recurrent depression subgroup, were analyzed. Severe baseline impairment was found in the Q-LES-Q and all subscales of the SF-36. A multivariate regression analysis identified depression as the strongest predictor of baseline quality-of-life impairment (partial r, -0.37, p = 0.001). In the recurrent depression group, treatment with sertraline resulted in significantly greater improvement than placebo in the Q-LES-Q total score and SF-36 mental component summary score, as well as the SF-36 role limitations, emotional, and mental health factors. Depression has a substantial negative impact on quality of life and functioning in patients hospitalized for acute coronary syndrome. Sertraline was associated with clinically meaningful improvement in multiple quality-of-life domains in patients with acute coronary syndrome and recurrent depression.

Acute Disease↗
PubMed2003

Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy.

BACKGROUND: Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity. Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART). METHODS AND RESULTS: Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (n=28) or placebo (n=36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, beta-thromboglobulin (betaTG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for betaTG (P=0.03) at weeks 6 and 16 and for P-selectin (P=0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and betaTG concentrations across the entire treatment period. CONCLUSIONS: Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.

Biomarkers↗
PubMed2003

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective analysis of the data from several clinical trials reveals that clinical depression is associated with enhanced activation of platelet/endothelial biomarkers even above the level expected in ACS. These findings may contribute to the unfavorable outcome associated with clinical depression in patients with ACS.

Acute Disease↗
PubMed2002

Sertraline treatment of major depression in patients with acute MI or unstable angina.

CONTEXT: Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease. OBJECTIVE: To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001. PATIENTS: A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%). INTERVENTION: After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks. MAIN OUTCOME MEASURES: The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD. RESULTS: Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline. CONCLUSION: Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.

Angina, Unstable↗
PubMed2002

A randomized trial of sertraline as a cessation aid for smokers with a history of major depression.

OBJECTIVE: Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated. METHOD: The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits. RESULTS: Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed. CONCLUSIONS: Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.

Adult↗
PubMed2002

Clinical management of cardiovascular risks during treatment with psychotropic drugs.

The treatment of schizophrenia--as well as dementia, psychotic depression, and bipolar disorder--was greatly improved by the development of new atypical antipsychotic drugs in the past decade. However, cardiovascular and metabolic risks that are associated with some of these agents have become worrisome to clinicians and researchers. In this article, I will review psychotropic and other agents that have been associated with cardiovascular changes during treatment. Screening for cardiac vulnerability at baseline, as well as at regular intervals during treatment if the patient has certain risk factors, is important when treating patients with psychotropic agents.

Aged↗
PubMed2002

Assessing cardiovascular risks versus clinical benefits of atypical antipsychotic drug treatment.

The atypical antipsychotic drugs are a major advance in the treatment of psychosis in spite of concerns about metabolic and cardiovascular side effects that affect morbidity and mortality. Concerns about weight gain, hypoglycemia, diabetes, and increases in lipids as well as sudden death due to torsades de pointes and other cardiovascular events can temper enthusiasm about the atypical antipsychotics. The challenge for the clinician is to weigh the benefits and risks for each drug for each patient and develop a treatment plan with the individual patient in mind. This article discusses both risks and benefits of antipsychotic treatment and presents a treatment algorithm to aid the clinician in choosing medications for the psychotic patient.

Algorithms↗
PubMedDate not supplied

Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report.

OBJECTIVE: The National Heart, Lung, and Blood Institute convened an interdisciplinary working group of experts to develop recommendations for the assessment and treatment of depression in patients with coronary heart disease (CHD). METHOD: Consensus of experts. RESULTS: Our current recommendations are that the Beck Depression Inventory-I be employed for epidemiological studies of depression and CHD, that the Patient Health Questionnaire 2-item version be employed for screening for trial eligibility, that the Depression Interview and Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial inclusion, and that the Hamilton rating scale, which is part of the DISH, be employed for both depression symptom reduction and the remission criterion in any trial. We further recommend that a randomized controlled trial be undertaken to determine whether selective serotonin reuptake inhibitors, psychotherapy, or combined treatment can reduce the risk of CHD events and mortality associated with depression in CHD patients. CONCLUSIONS: This report summarizes the recommendations made by the working group and discusses the rationale for each recommendation, the strengths and weaknesses of alternative approaches to assessment and treatment, and the implications for future research in this area.

Antidepressive Agents↗