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ABSTRACT: The CREATE trial reported that coronary artery disease (CAD) patients suffering from a first depression derived less benefit from citalopram relative to placebo than those with a recurrent depression. The present investigation sought to determine whether the differential benefit of citalopram between those with a first depression and those with recurrent depression could be explained by indicators of vascular depression and cardiac disease severity.
Secondary analyses of data from CREATE, a 12-week, randomized placebo-controlled trial of 284 patients with major depressive disorder and CAD were used. Recurrence subgroups were compared on baseline characteristics reflecting vascular depression and cardiac disease severity. Outcome measures were the mean change from baseline to 12 weeks on the 24-item Hamilton Depression Rating Scale administered centrally by telephone. ANCOVA was used to assess the potential interaction of each baseline variable with citalopram/placebo treatment in predicting outcomes.
Few baseline differences differentiated patients with a first versus recurrent depression, and none accounted for the differential treatment efficacy in these subgroups. Patients with a cardiac event in the past 6 months (P=.02) and taking angiotensin-converting enzyme inhibitors (P=.03) experienced less change with citalopram relative to placebo. Older age, worse functional status, taking beta-blockers, presence of angina (all P<.05), and later age of first depression (P=.05) predicted smaller changes in depression, independent of treatment assignment.
There was limited evidence that the lack of improvement with citalopram relative to placebo in CAD patients with a first depression can be attributed to vascular depression.
Journal of psychosomatic research 08/2010; 69(2):133-41. · 2.91 Impact Factor
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ABSTRACT: Major depressive disorder (MDD) associated with acute coronary syndrome (ACS) increases the risk of mortality. Decreased heart rate variability (HRV), also a predictor of mortality, is reduced in patients with MDD after ACS, and has been suggested to be a mediator of MDD mortality after ACS. Although selective serotonin reuptake inhibitors may reduce mortality post-ACS, little is known about their effects on HRV.
To examine the influence of both sertraline and improvement in mood on HRV.
The Sertraline Antidepressant Heart Attack Randomized Trial assessed HRV from 24-hour Holter electrocardiogram recordings at baseline in 290 patients and from a second recording in 258 of these patients 16 weeks after randomization to sertraline or placebo. Frequency domain measures of HRV included high-frequency power, low-frequency power, very low-frequency power, ultra low-frequency power, and total power. Depression severity was measured by the Hamilton Rating Scale for Depression. Clinical response was measured with the Clinical Global Impressions Improvement scale.
At baseline, prior episodes of MDD were associated with lower HRV. Sertraline significantly increased ultra low-frequency power, while improvement in mood was associated with higher low-frequency power independent of treatment. However, the expected recovery in HRV following ACS was not observed in patients with MDD. Higher ultra low-frequency during sertraline treatment and higher low-frequency power in patients whose mood improved resulted primarily from these measures decreasing in their comparison groups.
Heart rate variability recovery is impaired in depressed patients after ACS. Previously reported differences in baseline HRV between patients with and without depression after ACS grew larger in the 16 weeks following a coronary event. Both sertraline treatment and symptomatic recovery from depression were associated with increased HRV compared with placebo-treated and nonrecovered post-ACS control groups, respectively, but this results primarily from decreased HRV in the comparison groups.
Archives of General Psychiatry 10/2007; 64(9):1025-31. · 12.02 Impact Factor
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ABSTRACT: Antipsychotics are frequently used in the management of delirium, although there is limited information regarding the safety and efficacy of antipsychotics in treating delirium. The purpose of this study was to systematically evaluate the evidence for the efficacy and safety of antipsychotics in treating delirium.
MEDLINE (July 1980 to July 2005) and Cochrane databases were searched for English language articles using keywords.
Prospective studies with standardized criteria for diagnosing delirium and evaluating its severity.
In total, 14 studies (9 single agent studies and 5 comparison trials) met inclusion criteria. Study medications included haloperidol, chlorpromazine, olanzapine, risperidone, and quetiapine. Improvements in delirium severity were reported with all of these antipsychotic medications. No study included a placebo comparison to account for spontaneous improvements in delirium. Other methodological limitations included inadequate blinding, randomization, and handling of participant withdrawals. The improvements in delirium tended to occur soon after initiation of treatment, and most of the studies examined used relatively low doses of antipsychotic medication. Serious adverse events attributable to antipsychotic medication were uncommon in studies, although side effects were not evaluated systematically in most studies.
To date, there are no published double-blind, randomized, placebo-controlled trials to establish the efficacy or safety of any antipsychotic medication in the management of delirium. There is limited evidence from uncontrolled studies that supports the use of low-dose, short-term treatment of delirium with some antipsychotics. Further study with well-designed clinical trials is required in this area.
The Journal of Clinical Psychiatry 02/2007; 68(1):11-21. · 5.80 Impact Factor
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François Lespérance,
Nancy Frasure-Smith,
Diana Koszycki,
Marc-André Laliberté, Louis T van Zyl,
Brian Baker,
John Robert Swenson,
Kayhan Ghatavi,
Beth L Abramson,
Paul Dorian,
Marie-Claude Guertin
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ABSTRACT: Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy.
To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression.
The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 x 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher.
Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142).
The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .017).
Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (-2.26 points; 96.7% CI, -4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, -1.90 to 4.16; P = .37; effect size = 0.11).
This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression.
isrctn.org Identifier: ISRCTN15858091.
JAMA The Journal of the American Medical Association 02/2007; 297(4):367-79. · 30.03 Impact Factor
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ABSTRACT: To describe the administrative functioning of all current Canadian psychiatry residency training programs (RTPs) and to suggest available improvements to existing systems.
We obtained data about the 2004 RTPs by distributing 2 questionnaires to all Canadian psychiatry RTPs.
Residency program committees (RPCs) are mainly consultative and carry only a small amount of the workload of managing a residency program. Program directors (PDs) manage more than 80% of the work and report that the time allowance to perform their duties is suboptimal. PDs remain in office for about 5 years, departing during or at the end of a predetermined second term.
RPCs bear only a small amount of the workload generated by the RTP. We piloted administrative changes that led to more equitable work distribution.
Canadian journal of psychiatry. Revue canadienne de psychiatrie 06/2006; 51(6):377-81. · 2.42 Impact Factor
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ABSTRACT: Delirium is a common neuropsychiatric condition that affects 15% to 70% of elderly medical and surgical patients. It tends to be a transient disorder, although long-term complications are not uncommon. Medical comorbidity is the rule, and predisposing, as well as precipitating, factors are important to consider in its management. Major risk factors for delirium include advanced age, cognitive impairment, and chronic medical illness. Delirium is associated with several adverse outcomes including mortality, increased length of hospital stay, increased risk of dementia, and high rates of institutional placement. Delirium is distressing for patients, families, and staff. Nonpharmacologic-integrated intervention programs may improve outcome and may be incorporated into the overall medical management.
Geriatrics 04/2006; 61(3):18-21. · 1.35 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
American Journal of Psychiatry 07/2005; 162(6):1165-70. · 12.54 Impact Factor
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ABSTRACT: 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.
The American Journal of Cardiology 01/2004; 92(11):1271-6. · 3.37 Impact Factor
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ABSTRACT: Delirium, an important event in hospital, is associated with significant mortality and morbidity. Most patients with delirium recover fully; however, when left untreated, delirium may progress to stupor, coma, or death. Delirium is less likely to resolve completely in elderly patients in whom persistent cognitive deficits commonly occur. The extent to which this information is available to family doctors after discharge was investigated.
A total of 31 patients with delirium who were referred to consultation-liaison psychiatry were assessed using standardized measures. Medical services completed discharge summaries on these patients; a chart review captured the extent to which the diagnosis of delirium and the involvement of psychiatry was recorded in the discharge summaries.
In structured discharge summaries, a reference to delirium occurrence was found in 55% of cases. In unstructured discharge summaries, the reporting was much lower (16% of cases). Delirium was more likely to be reported in women than in men, when it was more severe, or when it was the principal reason for admission, rather than when it occurred during an admission for some other reason.
Delirium episodes that occur during a period of hospitalization for treatment of any medical disorder are underreported, even when specifically diagnosed. Structured discharge summaries tend to increase the rate of reporting.
Canadian journal of psychiatry. Revue canadienne de psychiatrie 10/2003; 48(8):555-60. · 2.42 Impact Factor
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Victor L Serebruany,
Alexander H Glassman,
Alex I Malinin,
Charles B Nemeroff,
Dominique L Musselman, Louis T van Zyl,
Mitchell S Finkel,
K Ranga R Krishnan,
Michael Gaffney,
Wilma Harrison,
Robert M Califf,
Christopher M O'Connor
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ABSTRACT: 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).
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.
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.
Circulation 09/2003; 108(8):939-44. · 14.74 Impact Factor
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Alexander H Glassman,
Christopher M O'Connor,
Robert M Califf,
Karl Swedberg,
Peter Schwartz,
J Thomas Bigger,
K Ranga Rama Krishnan, Louis T van Zyl,
J Robert Swenson,
Mitchell S Finkel,
Charles Landau,
Peter A Shapiro,
Carl J Pepine,
Jack Mardekian,
Wilma M Harrison,
David Barton,
Michael Mclvor
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ABSTRACT: 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.
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.
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.
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%).
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.
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.
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.
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.
JAMA The Journal of the American Medical Association 08/2002; 288(6):701-9. · 30.03 Impact Factor
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ABSTRACT: Canadian residency training programs (RTP) have a program director (PD) and a residency program committee (RPC) overseeing program administration. Limited guidance is available about the ideal administrative structure of an RTP. This article describes administrative load in Canadian RTPs, presents a novel approach to delegating core administrative tasks within the RTP, and provides initial impressions of positive outcomes following implementation of this new system.
All PDs of Canadian psychiatry RTPs were surveyed with respect to their program administrative structure, involvement of their training committees, and the percentage of work done by the PD compared to the rest of the RPC. At Queen's University, program domains were created representing well-defined areas within the RTP, each being assigned a program domain manager.
RPCs were mainly consultative, averaging 14 members. The average PD: RPC workload ratio was 80:20. Three programs allowed for 50% of the program director's time to be dedicated to serving that position, with an average time dedication of 37%.
The position of PD in psychiatry requires an average of 37% of the program director's time, while carrying an estimated 82% of the administrative workload. The program domain manager administration system implemented at Queen's University enabled the PD to be simultaneously up to date with all major areas of the program while experiencing a substantial decrease in the administrative workload, achieved through increased work contribution of the RPC. This system encourages closer involvement of RPC members in decision making and development of their program domains, allowing the PD more time for developing, implementing and overseeing innovations across the RTP spectrum. Furthermore, it has led to a PD: RPC workload shift from a ratio of 90:10 to one of about 60:40. Essentially, this resulted in a more efficient and adaptable RPC and RTP.
Academic Psychiatry 29(5):464-70. · 0.81 Impact Factor
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ABSTRACT: There is increasing evidence linking depression and cardiovascular disease. However, the authors could find no literature directly linking depression with atrial fibrillation or atrial flutter. The authors report the case of a patient with uncontrolled atrial arrhythmia who cardioverted to normal sinus rhythm after treatment of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) with venlafaxine. The authors discuss comorbidity of MDD and atrial fibrillation, and explore evidence of venlafaxine as an antiarrhythmic agent. Further research is needed to establish the clinical role of venlafaxine as a Class 1 antiarrhythmic agent and any association between atrial arrhythmias and MDD and PTSD.
Psychosomatics 47(6):533-6. · 2.12 Impact Factor
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ABSTRACT: Recognition that depression is associated with increased morbidity and mortality in coronary artery disease (CAD) patients has augmented the need for evidence-based treatment guidelines. This article presents the design of a multisite, Canadian trial of the efficacy, safety, and tolerability of interpersonal psychotherapy (IPT), an empirically supported, depression-focused therapy, and the selective serotonin reuptake inhibitor citalopram, alone or in combination, in the treatment of major depression in CAD patients.
Two hundred eighty stable CAD patients with a current major depressive episode of at least 4 weeks' duration, based on the Structured Clinical Interview for Depression (SCID), and who have a baseline score >19 on a centralized, telephone-administered, 24-item Hamilton Depression Rating Scale (HAM-D) will be randomly assigned to receive 12 weekly IPT sessions or 12 weekly sessions of standardized clinical management (CM). Patients are also randomly assigned to receive 20 to 40 mg per day of citalopram or pill-placebo. This results in a 2-by-2 factorial design with four groups: IPT plus pill-placebo, IPT plus citalopram, CM plus pill-placebo, and CM plus citalopram. This permits the evaluation of both IPT and citalopram. Blinded, centralized, 24-item, HAM-D telephone ratings constitute the primary outcome variable. The self-report Beck Depression Inventory-II is the secondary outcome. Analyses will involve the intent-to-treat principle with last observation carried forward for incomplete assessments.
Not applicable.
The results of this trial will contribute to the development of evidence-based clinical guidelines for managing depression in the context of CAD.
Psychosomatic Medicine 68(1):87-93. · 3.97 Impact Factor
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François Lespérance,
Nancy Frasure-Smith,
Diana Koszycki,
Marc-André Laliberté, Louis T. van Zyl,
Brian Baker,
John Robert Swenson,
Kayhan Ghatavi,
Beth L. Abramson,
Paul Dorian,
Marie-Claude Guertin,
for the CREATE Investigators
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ABSTRACT: Context
Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy.Objective
To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression.Design, Setting, and Participants
The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 × 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher.Interventions
Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142).Main Outcome Measures
The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at α = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at α = .017).Results
Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (−2.26 points; 96.7% CI, −4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, −1.90 to 4.16; P = .37; effect size = 0.11).Conclusions
This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression.Trial Registration
isrctn.org Identifier: ISRCTN15858091
Figures in this Article
Since the early 1990s, studies have reported prevalences of major depression between 17% and 27% in hospitalized patients with coronary artery disease (CAD).1 Most have also demonstrated that depression has a negative cardiac prognostic impact.2- 3 Only 1 large randomized trial, the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study,4 has tried to determine whether treating depression could improve cardiac prognosis in CAD patients. Although ENRICHD demonstrated that a combination of short-term individual cognitive behavior therapy (CBT) and a selective serotonin reuptake inhibitor (SSRI), when needed, was significantly better than usual care at reducing depressive symptoms over 6 months in depressed or socially isolated myocardial infarction patients, the effect size was small. The study failed to show that the ENRICHD treatment protocol was better than usual care in preventing all-cause mortality and recurrent myocardial infarctions.
While there is a clear need for additional studies evaluating interventions to prevent the cardiac prognostic impact of depression,5- 6 there have also been few adequately controlled trials evaluating whether depression treatments are effective in reducing depressive symptoms in patients with CAD.7- 8 The largest of these, the Sertraline Antidepressant Heart Attack Trial (SADHART),8 provided some evidence of the safety of sertraline in patients recently hospitalized for an acute coronary syndrome. However, the overall efficacy results were less convincing. Planned subgroup analyses showed a clear benefit of sertraline over placebo for patients with recurrent depression and those with more severe depression. Additional post hoc analyses showed that patients whose depression began before the index cardiac event benefited more from sertraline than those with more recent depression onset.9
The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) is the first trial specifically designed to evaluate the short-term efficacy and tolerability of 2 depression treatments in patients with CAD: citalopram, a first-line SSRI antidepressant10 and interpersonal psychotherapy (IPT),11 a short-term, manual-based psychotherapy focusing on the social context of depression. To help ensure the applicability of results to a wide group of cardiac patients, recruitment was not restricted to patients with a recent acute coronary syndrome hospitalization.
JAMA The Journal of the American Medical Association 297(4):367-379. · 30.03 Impact Factor
