Heart rate variability in acute coronary syndrome patients with major depression: influence of sertraline and mood improvement.

CONTEXT: 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. OBJECTIVE: To examine the influence of both sertraline and improvement in mood on HRV. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

L-Tryptophan As Treatment for Pediatric Non-Rapid Eye Movement Parasomnia.

OBJECTIVE: Parasomnias are common in childhood but there is no established treatment for parasomnias. The aim of this study was to (1) report on the outcome of using L-tryptophan to manage parasomnias in children and (2) examine sleep architecture and subjective psychological/sleep symptoms in children with parasomnia. METHOD: A retrospective analysis was conducted of charts of children (3-18 years old) who underwent polysomnographic testing and were diagnosed with primary parasomnia. Study patients were either prescribed L-tryptophan (daily dose range: 500-4500 mg, mean dose of 2400 mg) to manage their parasomnias or administered no treatment whereby parents/guardians declined treatment. Questionnaires assessing sleep and psychosocial symptoms were administered at the initial clinical consultation and a follow-up parasomnia outcome questionnaire was administered over the phone to parents/guardians. RESULTS: One hundred and sixty-five children (106 boys, 59 girls) received a sleep diagnosis of primary parasomnia. A significantly (p < 0.001) higher proportion (84%) of children taking L-tryptophan experienced improvements in their parasomnia symptoms compared with those (47%) who chose not to use L-tryptophan. Polysomnography revealed that children with parasomnias had an altered sleep architecture based on age-related normative values. Children with a diagnosis of parasomnia were also subjectively more fatigued and endorsed more depressive symptoms. CONCLUSIONS: This study finds that parasomnias in children are not benign and that treatment with L-tryptophan provides a favorable outcome. Children diagnosed with parasomnia had altered sleep architecture, were more fatigued, and endorsed depressive symptoms. This study supports the need to diagnose and treat parasomnias in children.

Antiplatelet properties of escitalopram in patients with the metabolic syndrome: a dose-ranging in vitro study.

There is an increasing body of evidence suggesting that selective serotonin reuptake inhibitors exhibit clinical benefit beyond treating depression, by simultaneously inhibiting platelet activity. We recently demonstrated that escitalopram (ESC), but not its major metabolites, inhibits multiple platelet biomarkers in healthy volunteers. Considering that the metabolic syndrome represents one of the major risk factors for vascular disease, we here determined how ESC affects platelet activity in such patients. We assessed the in vitro effects of preincubation with escalating (50-200 nM/l) concentrations of ESC on platelet aggregation, expression of major surface receptors by flow cytometry, and quantitatively by platelet function analyzers. Blood samples were obtained from 20 aspirin-naïve patients with documented metabolic syndrome. Pretreatment of blood samples with medium (150 nM/l), or high (200 nM/l) doses of ESC resulted in a significant inhibition of platelet aggregation induced by ADP (p=0.007) and by collagen (p=0.004). Surface platelet expression of GPIb (CD42, p=0.03), LAMP-3 (CD63, p=0.04), and GP37 (CD165, p=0.03) was decreased in the ESC-pretreated samples. Closure time by the PFA-100 analyzer was prolonged after the 200 nM/l dose (p=0.02), indicating platelet inhibition under high shear conditions. On the other hand, the lowest tested concentration of ESC (50 nM/l) did not affect platelet activity in these patients. The in vitro antiplatelet characteristics of ESC in patients with the metabolic syndrome are similar to those in healthy volunteers. However, higher ESC doses are required to induce equally potent platelet inhibition. These data justify prospective ex vivo studies with the highest therapeutic dose to determine the potential clinical advantage of ESC in high-risk patients with vascular disease.

Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial.

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 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. 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 alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .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.

Design and rationale for a randomized, controlled trial of interpersonal psychotherapy and citalopram for depression in coronary artery disease (CREATE).

OBJECTIVE: 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. METHODS: 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. RESULTS: Not applicable. CONCLUSIONS: The results of this trial will contribute to the development of evidence-based clinical guidelines for managing depression in the context of CAD.

Delirium concisely: condition is associated with increased morbidity, mortality, and length of hospitalization.

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.

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.

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.

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.

Cefditoren pivoxil versus cefpodoxime proxetil for community-acquired pneumonia: results of a multicenter, prospective, randomized, double-blind study.

BACKGROUND: According to recently issued treatment guidelines, appropriate empiric choices for ambulatory patients with community-acquired pneumonia (CAP) are a macrolide, doxycycline (for patients aged > or = 8 years), or an oral beta-lactam agent with good activity against pneumococci. OBJECTIVE: This study was designed to compare cefditoren pivoxil, a new beta-lactam, with cefpodoxime proxetil, a beta-lactam with an established role in the treatment of CAP. METHODS: This was a multicenter, prospective, randomized, double-blind study conducted in the United States and South Africa. Ambulatory patients with a diagnosis of CAP were randomized to 14 days of treatment with cefditoren 200 or 400 mg BID or cefpodoxime 200 mg BID. Assessments of clinical cure and pathogen eradication were conducted at 2 visits during treatment, 1 posttreatment visit (s48 hours after completion of treatment), and 1 follow-up visit (7-14 days after completion of treatment). The development of resistant pathogens was assessed at the follow-up visit but not thereafter. The relative cost of treatment was not assessed. RESULTS: The study enrolled 851 patients. Comparable clinical cure rates were observed among evaluable patients in the 3 treatment groups at both the posttreatment and followup visits: at the posttreatment visit, cure rates were 90.5% (162/179) for cefditoren 200 mg, 89.7% (148/165) for cefditoren 400 mg, and 92.2% (153/166) for cefpodoxime 200 mg; at the follow-up visit, they were a respective 88.4% (160/181), 87.2% (143/164), and 90.4% (151/167). Of the 171 strains of Streptococcus pneumoniae isolated before treatment, 22 (12.9%) had reduced susceptibility to penicillin, 5 (2.9%) of them penicillin resistant (minimum inhibitory concentration > or = 2 microg/mL). At the posttreatment visit, the overall eradication rates of pathogens isolated from microbiologically evaluable patients were 88.7% (134/151), 89.9% (134/149), and 95.7% (134/140) in the respective treatment groups (P = 0.031, cefditoren 200 mg vs cefpodoxime). Eradication rates of S pneumoniae were 93.8% (45/48), 95.7% (45/47), and 95.6% (43/ 45) in the respective treatment groups; those of Haemophilus influenzae were 90.2% (46/51), 97.7% (43/44), and 97.4% (37/38). The rates of resolution and/or improvement in clinical signs and symptoms were comparable between groups. The study drugs were well tolerated, with 1.7%, 2.5%, and 1.4% of patients in the respective groups discontinuing study drug prematurely due to a treatment-related adverse event, the majority of these associated with the digestive system. CONCLUSION: The results of this study suggest that cefditoren may have a role in the treatment of CAP in ambulatory patients.

First episode of major depressive disorder and vascular factors in coronary artery disease patients: Baseline characteristics and response to antidepressant treatment in the CREATE trial.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Platelet and endothelial activity in comorbid major depression and coronary artery disease patients treated with citalopram: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial (CREATE) biomarker sub-study.

BACKGROUND AND PURPOSE: Major depression is an independent risk factor for increased morbidity and mortality in patients with coronary artery disease (CAD). Increased platelet activity and vascular endothelial dysfunction are possible pathways through which depression may increase cardiovascular risk. Citalopram exhibits strong selective inhibition of human platelet activation, but little is known about its effects on vascular endothelium. We assessed whether treatment of depressed CAD patients with citalopram alters platelet/endothelial biomarkers. The study was performed within the framework of the CREATE trial. METHODS: We assessed the effect of citalopram on P-selectin, beta-thromboglobulin (betaTG), soluble intercellular cell adhesion molecule-1 (sICAM-1), and total nitric oxide (tNO). Plasma samples were obtained at baseline and week 12 from subjects randomized to citalopram 20-40 mg daily (n = 36), or placebo (n = 21). Anticoagulants, aspirin, and clopidogrel were permitted. RESULTS: Treatment with citalopram was associated with greater increase in tNO over 12 weeks compared to placebo (P = 0.005). There were no differences for the other biomarkers such as P-selectin (P = 0.70), betaTG (P = 0.46) and ICAM (P = 0.59). CONCLUSION: Treatment with citalopram for 12 weeks in depressed CAD patients is associated with enhanced production of nitric oxide despite the co-administration of commonly prescribed anti-platelet regimens including aspirin and clopidogrel. Clinical implications of these findings are unclear, but improved endothelial function is implied by the increased NO production, suggesting that citalopram may be of particular benefit for patients with comorbid depression and vascular disease including CAD, stroke, peripheral artery disease, and diabetes.

Effects of antidepressant treatment on heart rate variability in major depression: a quantitative review.

BACKGROUND: The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed. METHODS: Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately. RESULTS: Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times.Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported. LIMITATIONS: Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies. CONCLUSION: We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.

Antipsychotics in the treatment of delirium: a systematic review.

OBJECTIVE: 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. SOURCES: MEDLINE (July 1980 to July 2005) and Cochrane databases were searched for English language articles using keywords. STUDY SELECTION: Prospective studies with standardized criteria for diagnosing delirium and evaluating its severity. DATA SYNTHESIS: 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. CONCLUSION: 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.

Fluorimetric quantitation of citalopram and escitalopram in plasma: developing an express method to monitor compliance in clinical trials.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) in general, and citalopram/escitalopram in particular, are widely used to treat clinical depression. However, SSRI bioavailability and non-compliance represent major issues, especially in the clinical trials setting. In this context, frequent drug-level measurements for compliance monitoring would be a desirable tool to improve clinical outcomes with SSRIs. However, the liquid chromatography techniques available are expensive, requiring excessive sample preparation, and suffer from high complexity. We sought to develop a rapid method for the measurement of citalopram/escitalopram levels in human plasma by fluorimetry. METHODS: A total of 34 frozen human plasma samples were thawed at room temperature and repeatedly centrifuged in cellulose to remove aggregates, proteins and solids. Fluorescence spectra were measured in the range 270-450 nm with excitation at 240 nm on a FluoroMax 3 spectrofluorimeter. Control samples contained known concentrations of SSRIs. RESULTS: SSRI absorbance spectra were recorded in the range 230-320 nm. The shape of the spectra and the absorbance of citalopram and escitalopram were very similar, with UV maximum absorbance at 239 nm. The maximum extinction coefficient was epsilon239=15,930 M-1 cm-1 for citalopram and epsilon239=13,630 M-1 cm-1 for escitalopram. The fluorescence spectra of SSRIs are unique and are characterized by the presence of two well-defined conjugated spectra with maxima at 300 and 382 nm. CONCLUSIONS: Fluorimetry is very suitable for assessment of plasma SSRI levels. This inexpensive and efficient technique can objectively and reliably quantify drug levels in biological fluids, thereby directly determining the level of patient adherence to the prescribed drug regimen. This method will be useful in a broad spectrum of applications, from compliance/bioavailability assessments in animal and human experiments to utilization in large-scale clinical trials.

Cardioversion of persistent atrial arrhythmia after treatment with venlafaxine in successful management of major depression and posttraumatic stress disorder.

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.

Canadian psychiatry residency training programs: A glance at the management structure.

OBJECTIVES: To describe the administrative functioning of all current Canadian psychiatry residency training programs (RTPs) and to suggest available improvements to existing systems. METHOD: We obtained data about the 2004 RTPs by distributing 2 questionnaires to all Canadian psychiatry RTPs. RESULTS: 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. CONCLUSION: RPCs bear only a small amount of the workload generated by the RTP. We piloted administrative changes that led to more equitable work distribution.

Escitalopram, but not its major metabolites, exhibits antiplatelet activity in humans.

BACKGROUND: Clinical depression has been identified as an independent risk factor for increased mortality during follow-up in patients suffered from acute coronary events, whereas increased platelet activity has been proposed as one of the mechanisms for this association. Some evidence suggests that selective serotonin reuptake inhibitors and/or their metabolites exhibit potent antiplatelet properties. METHODS: We assessed the in vitro effects of preincubation with escalating (50-200 nmol/L) concentrations of escitalopram (ESC) S-desmethyl-citalopram (S-DCT), and S-di-desmethyl-citalopram, (S-DCT) on platelet aggregation through the expression of major surface receptors using flow cytometry and quantitatively using platelet function analyzers in 20 healthy volunteers. RESULTS: Pretreatment of blood samples with ESC with ESC resulted in a significant inhibition of platelet aggregation induced by ADP (P = 0.0001) and by collagen with the highest dose (P = 0.001). Surface platelet expressions of glycoprotein Ib (CD42) (P = 0.04), lysosome associated membrane protein-3 (CD63) (P = 0.02), and GP37 (CD165) (P = 0.03) was decreased in the ESC-pretreated samples. Closure time by the Platelet Function Analyzer-100 analyzer was prolonged for the 200 nmol/L dose (P = 0.02), indicating platelet inhibition under high shear conditions. Two major metabolites of ESC, namely S-DCT and S-DDCT, did not affect platelet activity. CONCLUSION: Escitalopram, but not its metabolites, exhibited selective inhibition of human platelet properties. The direct antiplatelet effect of ESC requires further prospective or ex vivo testing to determine the possible clinical advantage of this finding.

Administrative restructuring of a residency training program for improved efficiency and output.

OBJECTIVES: 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. METHOD: 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. RESULTS: 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%. CONCLUSION: 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.

Delirium in hospital: an underreported event at discharge.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.