Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

AIM: Treatment-resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health-care costs than non-affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment-resistant depression based on prior work in animals and humans. METHODS: Twelve subjects with mild or moderate treatment-resistant depression were randomized into a double-blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5-day washout in between the 8-day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire-9. RESULTS: We found a difference in serum magnesium from day 2 to 8 (pre-infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire-9 24 h post-treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire-9 decreased from baseline to day 7 (P = 0.02). CONCLUSION: Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge.

Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review.

BACKGROUND: Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. OBJECTIVES: We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. METHODS: We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. RESULTS: In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have more than double the prevalence of steatohepatitis or rejection on biopsy and graft failure and more frequent mortality resulting from recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest drinking at 6y posttransplantation) alcohol users do. Fortunately, pretransplantation screening combined with a structured pretransplantation management program and a 12-step program attendance reduced recidivism. No randomized clinical trials have been performed that target pretransplantation risk factors in individuals with alcoholic liver disease before or after OLT to improve post-OLT outcomes. CONCLUSIONS: Recent research findings suggest that screening can reveal individuals who are vulnerable to alcohol relapse and targeted intervention can prevent their relapse to alcohol. Based on existing addiction treatments (e.g., relapse prevention plan construction), randomized clinical trials tailored to post-OLT patients should be conducted to improve their survival and quality of life.

The biology of depression in cancer and the relationship between depression and cancer progression.

The prevalence of depressive symptoms in patients with cancer exceeds that observed in the general population and depression is associated with a poorer prognosis in cancer patients. The increased prevalence is not solely explained by the psychosocial stress associated with the diagnosis. Pro-inflammatory cytokines, which induce sickness behaviour with symptoms overlapping those of clinical depression, are validated biomarkers of increased inflammation in patients with cancer. A growing literature reveals that chronic inflammatory processes associated with stress may also underlie depression symptoms in general, and in patients with cancer in particular. Therapeutic modalities, which are frequently poorly tolerated, are used in the treatment of cancer. These interventions are associated with inflammatory reactions, which may help to explain their toxicity. There is evidence that antidepressants can effectively treat symptoms of depression in cancer patients though the database is meager. Novel agents with anti-inflammatory properties may be effective alternatives for patients with treatment-resistant depression who exhibit evidence of increased inflammation.

Decision-making in diabetes mellitus type 1.

Decreased treatment adherence in patients with diabetes mellitus type 1 (type 1 DM) may reflect impairments in decision-making and underlying associated deficits in working memory and executive functioning. Other factors, including comorbid major depression, may also interfere with decision-making. The authors sought to review the clinically relevant characteristics of decision-making in type 1 DM by surveying the literature on decision-making by patients with type 1 DM. Deficiencies in decision-making in patients with type 1 DM or their caregivers contribute to treatment nonadherence and poorer metabolic control. Animal models of type 1 DM reveal deficits in hippocampal-dependent memory tasks, which are reversible with insulin. Neurocognitive studies of patients with type 1 DM reveal lowered performance on ability to apply knowledge to solve problems in a new situation and acquired scholarly knowledge, psychomotor efficiency, cognitive flexibility, visual perception, speed of information-processing, and sustained attention. Other factors that might contribute to poor decision-making in patients with type 1 DM, include "hypoglycemia unawareness" and comorbid major depression (given its increased prevalence in type 1 DM). Future studies utilizing novel treatment strategies to help patients with type 1 DM make better decisions about their disease may improve their glycemic control and quality of life, while minimizing the impact of end-organ disease.

Treatment of depression in individuals living with HIV/AIDS.

BACKGROUND: Depression is common in patients with HIV/AIDS, and can have an impact on quality of life, as well as various health outcomes. This study was designed to observe the efficacy of standard treatment of depression in human immunodeficiency virus (HIV) (+) individuals in an urban psychiatric clinic. METHODS: This study consisted of a retrospective chart review of patients presenting for psychiatric services between January 1, 2008 and December 31, 2010. A total of 211 charts were examined for factors including diagnosis given at initial visit, health status, sociodemographic factors and comorbid illnesses, as well as treatment plan prescribed; of these, 132 patients were determined to be depressed at the initial evaluation (Beck Depression Inventory (BDI> 13) and to return for at least one follow-up visit. RESULTS: Of the 132 depressed patients, 48 (36.4%) reached remission (BDI <13) at some point at follow-up, and an additional 12 (50.7%) achieved response (decrease in BDI of 50%). Remission correlated with having disability income and having a viral load that was not detectable. CONCLUSIONS: Depression is common in HIV/AIDS, and is important to treat. Furthermore, individuals with depression and HIV/AIDS respond at rates similar to what is seen in other depressed populations.

Depression and platelet activation in outpatients with stable coronary heart disease: findings from the Heart and Soul Study.

Depression is associated with increased morbidity and mortality in patients with coronary heart disease (CHD). Increased platelet activation has been proposed as a potential mechanism by which depression may lead to adverse cardiovascular outcomes. In this cross-sectional study, we measured platelet activation in 104 patients with stable CHD, including 58 with a current episode of major depression and 46 without past or current major depression. Participants were instructed not to take aspirin for 7 days prior to the study appointment. Platelet activation was measured by plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), and by 24-h urinary concentrations of 11-dehydro-thromboxane B(2) (TBXB2). We observed no differences in the mean levels of PF4, B-TG or TBXB2 in patients with and without major depression. Results were unchanged after adjustment for age, smoking, use of aspirin, and use of any psychotropic medication. We found no evidence of an association between major depression and platelet activation as measured by plasma concentrations of PF4 and beta-TG, or urinary TBXB2 in 104 outpatients with stable CHD. These findings do not support a role for platelet activation in the association between depression and cardiovascular disease among patients with stable CHD.

Stress, depression, and coronary artery disease: modeling comorbidity in female primates.

Depression and coronary heart disease (CHD) are leading contributors to disease burden in women. CHD and depression are comorbid; whether they have common etiology or depression causes CHD is unclear. The underlying pathology of CHD, coronary artery atherosclerosis (CAA), is present decades before CHD, and the temporal relationship between depression and CAA is unclear. The evidence of involvement of depression in early CAA in cynomolgus monkeys, an established model of CAA and depression, is summarized. Like people, monkeys may respond to the stress of low social status with depressive behavior accompanied by perturbations in hypothalamic-pituitary-adrenal (HPA), autonomic nervous system, lipid metabolism, ovarian, and neural serotonergic system function, all of which are associated with exacerbated CAA. The primate data are consistent with the hypothesis that depression may cause CAA, and also with the hypothesis that CAA and depression may be the result of social stress. More study is needed to discriminate between these two possibilities. The primate data paint a compelling picture of depression as a whole-body disease.

Depression and whole blood serotonin in patients with coronary heart disease from the Heart and Soul Study.

OBJECTIVE: To evaluate whether depression is associated with whole blood serotonin in outpatients with stable coronary heart disease (CHD). Depression is associated with incident CHD and with adverse cardiovascular outcomes. Dysregulation of peripheral serotonin, common to both depression and CHD, may contribute to this association. METHODS: We performed a cross-sectional study of 791 participants with stable CHD enrolled in the Heart and Soul Study and not taking antidepressant medication. We assessed major depression using the Computerized Diagnostic Interview Schedule (CDIS-IV) and measured whole blood serotonin (WBS) from fasting venous samples. RESULTS: Of the 791 participants, 114 (14%) had current (past month) major depression, 186 (24%) had past (but not current) major depression, and 491 (62%) had no history of depression. Age-adjusted mean WBS was higher in participants with current major depression (139 +/- 6.5 ng/ml) than in those with past depression (120 +/- 5.0 ng/ml) or no history of depression (119 +/- 3.1 ng/ml) (p = .02). This association was unchanged after adjustment for demographic characteristics, medical comorbidities, medication use, and cardiac disease severity (p = .02). When serotonin was analyzed as a dichotomous variable, current depression was associated with a 70% greater odds of having WBS in the highest quartile (adjusted odds ratio = 1.71; 95% Confidence Interval = 1.03-2.83; p = .04). CONCLUSIONS: In this sample of patients with stable CHD, current major depression was independently associated with higher mean WBS levels. Future studies should examine whether elevated WBS may contribute to adverse outcomes in patients with depression and CHD.

Sequential multiple-assignment randomized trial design of neurobehavioral treatment for patients with metastatic malignant melanoma undergoing high-dose interferon-alpha therapy.

BACKGROUND: Interferon-alpha therapy, which is used to treat metastatic malignant melanoma, can cause patients to develop two distinct neurobehavioral symptom complexes: a mood syndrome and a neurovegetative syndrome. Interferon-alpha effects on serotonin metabolism appear to contribute to the mood and anxiety syndrome, while the neurovegetative syndrome appears to be related to interferon-alpha effects on dopamine. PURPOSE: Our goal is to propose a design for utilizing a sequential, multiple assignment, randomized trial design for patients with malignant melanoma to test the relative efficacy of drugs that target serotonin versus dopamine metabolism during 4 weeks of intravenous, then 8 weeks of subcutaneous, interferon-alpha therapy. METHODS: Patients will be offered participation in a double-blinded, randomized, controlled, 14-week trial involving two treatment phases. During the first month of intravenous interferon-alpha therapy, we will test the hypotheses that escitalopram will be more effective in reducing depressed mood, anxiety, and irritability, whereas methylphenidate will be more effective in diminishing interferon-alpha-induced neurovegetative symptoms, such as fatigue and psychomotor slowing. During the next 8 weeks of subcutaneous interferon therapy, participants whose symptoms do not improve significantly will be randomized to the alternate agent alone versus escitalopram and methylphenidate together. RESULTS: We present a prototype for a single-center, sequential, multiple assignment, randomized trial, which seeks to determine the efficacy of sequenced and targeted treatment for the two distinct symptom complexes suffered by patients treated with interferon-alpha. LIMITATIONS: Because we cannot completely control for external factors, a relevant question is whether or not 'short-term' neuropsychiatric interventions can increase the number of interferon-alpha doses tolerated and improve long-term survival. CONCLUSIONS: This sequential, multiple assignment, randomized trial proposes a framework for developing optimal treatment strategies; however, additional studies are needed to determine the best strategy for treating or preventing neurobehavioral symptoms induced by the immunotherapy interferon-alpha.

The effects of roux en y gastric bypass surgery on neurobehavioral symptom domains associated with severe obesity.

BACKGROUND: Neurobehavioral symptoms and cognitive dysfunction related to mood disorders are present in individuals with severe obesity. We sought to determine acute improvements in these symptoms and relationships with adiposity, inflammation, and insulin sensitivity after roux-en-y gastric bypass (RYGB) surgery. METHODS: The self-report Zung Depression Rating (ZDRS) and Neurotoxicity Rating (NRS) scales were administered before, and at 6-months after RYGB surgery in severely obese women (body mass index > 35 kg/m2; N = 19). Symptom domains corresponding to depressed mood/suicide ideation, anxiety, cognitive, somatic, and neurovegetative symptoms were assessed. Biologic measures were of adiposity [leptin, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue], inflammation [IL-6, C-reactive protein (CRP)], and insulin sensitivity (Si). Spearman correlations and linear regression (adjusted for biologic measures) assessed relationships between changes in biologic measures and changes in neurobehavioral domains. RESULTS: By 6-months after RYGB, VAT, SAT, Si, CRP, and IL-6 had improved (p < .05). Anxiety, somatic, and neurovegetative symptoms domains improved (p < .05), but depressed mood/suicidal ideation and cognitive domains did not. Reductions in VAT were associated with decreases in neurovegetative symptoms (beta = 295 ±â€¯85, p < .01). We also found significant positive longitudinal associations between IL-6 concentrations and minor changes in cognitive symptoms. CONCLUSION: Anxiety, somatic and neurovegetative symptoms, improved within 6 months after RYGB, but depressed mood/suicidal ideation and cognitive symptoms did not improve. Associations between visceral adiposity, IL-6 concentrations and neurovegetative and cognitive symptoms support links between obesity, inflammation and distinct neurobehavioral symptoms.

A multidimensional analysis of the longitudinal effects of roux en y gastric bypass on fatigue: An association with visceral obesity.

BACKGROUND AND OBJECTIVES: Severe obesity is associated with fatigue, however, the effects of weight loss after bariatric surgery on particular dimensions of fatigue are unknown. In a secondary analysis of a prospective cohort study of women undergoing roux-en-y gastric bypass (RYGB) we explored relationships among multiple dimensions of fatigue and improving adiposity, insulin resistance and inflammation. METHODS: Before, and 1 and 6 months after RYBG, dimensions of fatigue were assessed using the validated, self-report, Multidimensional Fatigue Inventory. Total, abdominal visceral (VAT) and subcutaneous (SAT) adiposity, insulin sensitivity (Si and HOMA) and plasma concentrations of leptin, C-reactive protein (CRP) and interleukin-6 (Il-6) were measured using air displacement plethysmography, computed tomography, glucose tolerance testing and enzyme-linked immunoassay. Associations were assessed using Spearman correlations and linear regression. RESULTS: At baseline, the majority of our female participants (N = 19, body mass index, 46.5 kg/m2, age 37.2 years) were experiencing elevated levels of fatigue. By 6 months, dimensions of physical (-43%), reduced activity (-43%), reduced motivation (-38%), general (-31%; all p < .005), and mental (-18%, p < .05) fatigue improved, concomitant with decreases in markers of adiposity, inflammation and insulin resistance. The decrease in VAT was associated with improvement in mental fatigue (beta, 0.447 ±â€¯0.203, p = .045), independent of other indices of adiposity, IL-6 concentrations, or Si. CONCLUSIONS: In the 6 months after RYGB, fatigue improved, especially physical fatigue. Decreases in mental fatigue were strongly associated with decreases in visceral adiposity. Nevertheless, the biologic mechanisms underlying changes in these specific fatigue dimensions remain undetermined.

Platelet thromboxane A2 secretion in patients with major depression responsive to electroconvulsive therapy.

OBJECTIVE: To determine a) whether clinical response to electroconvulsive therapy (ECT) is associated with decreased platelet activation in patients with major depressive disorder (MDD) and b) if any medical/demographic characteristics predict response to ECT or changes in platelet activation. Increased platelet activation may underlie the increased risk of coronary artery disease (CAD) in patients with MDD. METHODS: Before their first and sixth ECT treatments, study patients (n = 44) completed the Beck Depression Inventory (BDI) to assess the severity of depressive symptoms. Activity of the platelet thromboxane (TBX) A(2) pathway was assessed by measuring the morning spot urinary concentrations of 11-dehydroxy-thromboxane B(2) (11-D-TBX B(2)), a major metabolite of platelet-derived TBX A(2). RESULTS: Multivariate logistic regression analyses revealed that improvement on the BDI was significantly more likely in patients without a history of hypertension (p = .02) and in patients who were prescribed a greater number of "platelet-altering" medications (p = .03). During a course of ECT, a decrease in urinary 11-D-TBX B(2) was significantly more likely to occur in ECT nonresponders (p = .01) and younger patients (p = .02). CONCLUSIONS: Clinical response to ECT coadministered may not be associated with decreases in platelet-derived TBX. Future studies will confirm which somatic "antidepression" treatments offer optimal thrombovascular benefits for depressed patients with multiple risk factors for, or clinically evident, cerebral disease or CAD.

Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.

OBJECTIVE: Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown. METHODS: We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test. RESULTS: At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance. CONCLUSIONS: This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.

Seizure Induced by a Therapeutic Dose of Venlafaxine ER: A Case Report.

Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor commonly used for the treatment of depression. Although listed as an adverse reaction, seizure activity associated with a therapeutic dose of venlafaxine has rarely been documented. A review of the literature reveals only 2 cases of venlafaxine-induced seizures, both of which were generalized tonic-clonic seizures in patients on doses at the higher end of the therapeutic range. We report the case of a 44-year-old woman undergoing antituberculosis therapy who suffered complex partial seizures after ingestion of a low therapeutic dose of venlafaxine extended release (ER). Her first seizure was observed soon after venlafaxine ER was titrated from 37.5 to 75 mg daily, with a total of 9 witnessed complex partial seizures. After titrating the dose of the venlafaxine ER back down to 37.5 mg daily and beginning lamotrigine anticonvulsant therapy, the patient exhibited no further seizures. The development of seizure activity under therapeutic dosing of venlafaxine should be brought to the attention of the health care prescriber. The potential for drug-drug interactions involving venlafazine, particularly in combination with multiple drugs, such as isoniazid and levofloxacin, needs to be recognized.

Intravenous infusion of magnesium sulfate is not associated with cardiovascular, liver, kidney, and metabolic toxicity in adults.

BACKGROUND: Magnesium (Mg) deficiency contributes to the pathophysiology of numerous diseases. The therapeutic use of Mg has steadily increased over time. The increased in-hospital use of intravenous (IV) magnesium sulfate (MgSO4) warrants more extensive investigation regarding the safety of the therapy. The aim of this study was to determine the safety of IV MgSO4 infusion on cardiovascular, liver, kidney, and metabolic markers in adults. METHODS: Twelve volunteers were randomized to one of two cross-over conditions: (a) IV infusion of MgSO4 in 5% dextrose followed by IV infusion of 5% dextrose 1 week later or (b) IV infusion of 5% dextrose followed by IV infusion of MgSO4 in 5% dextrose 1 week later. An electrocardiogram was recorded continuously during the infusions. Blood was drawn pre- and post-infusion for blood count (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides). Results: Serum Mg increased from pre- to post-infusion in the MgSO4 + 5% dextrose group (p < 0.0001). The QRS interval length increased from pre- to post-infusion in the MgSO4 + 5% dextrose group (p < 0.04). Additionally, serum glucose concentration increased in the MgSO4 + 5% dextrose group (p = 0.04). These significant findings were modeled with gender and age as covariates. No other significant differences were found. CONCLUSIONS: The administration of IV infusion of MgSO4 (4 g/100 mL) in 5% dextrose over a 4-hour treatment period poses no significant deleterious effects on cardiovascular, liver, kidney, or metabolic function. RELEVANCE FOR PATIENTS: IV infusion of MgSO4 may be used for certain treatment indications without significant concern for systemic or organ toxicity.

Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress.

OBJECTIVE: The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress. METHOD: Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test. RESULTS: Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress. Natural killer (NK) cell percentages also increased following stress. However, there were no differences between groups and no correlation between NK cell percentage and stress-induced NF-kappaB DNA-binding or IL-6. CONCLUSIONS: Male major depression patients with increased early life stress exhibit enhanced inflammatory responsiveness to psychosocial stress, providing preliminary indication of a link between major depression, early life stress and adverse health outcomes in diseases associated with inflammation.

A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.

OBJECTIVE: This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. METHOD: In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. RESULTS: Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. CONCLUSION: The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.

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.

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.