Article

Aspirin for prevention of cardiovascular events in bipolar disorders

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  • Université Paris-Est Créteil Val de Marne - Inserm- AP-HP
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... Putative factors underlining the link between BD and metabolic syndrome include behavioural features, shared metabolic derangements, and adverse effects of antipsychotics. Valproate and olanzapine are widely used as mood stabilizers in BDs, which could trigger weight gain and diabetes, conditions that enhance risk of mortal cardiovascular events (Fond et al., 2014). ...
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Neuropsychiatric disorders place a very high burden on the global health and economy. The efficacies of currently available drugs in the psychiatric armamentarium are suboptimal and almost all of them target several neurotransmitter pathways. But it is more and more recognized that the neuroinflammation and associated oxidative pathways are important players in the etiopathogenesis of psychiatric disorders. In parallel to this new concept, recent investigations indicate that adjunction of acetylsalicylic acid (ASA) to the orthodox psychiatric treatments augments therapeutic efficacy in bipolar disorder and schizophrenia. Gentisic acid is a redox active quinonoid ASA metabolite and an endogenously produced siderophore with much more potent antioxidant effects than its parent compound. Moreover, it harbours molecular features that provide its selective conversion to even more potent anti-inflammatory quinonoid molecules within the inflammatory micromilieu. We believe that ASA alone and its combination with gentisic acid should be studied in animal models of psychiatric disorders to reveal their potential in regard to the augmentation of currently available treatments. If several animal studies prove their potential, clinical trials could easily be conducted, as both ASA and gentisic acid have a relatively high biosafety and a long history of clinical use. Behavioural Pharmacology 30: 627-641
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Objective: The weight impact produced by the atypical antipsychotic olanzapine has been explored in meta- analyses focusing on patients with schizophrenia. However, outcomes identified for schizophrenia patients cannot always be generalized to patients with bipolar disorder. This study aims to quantitatively estimate the impact of olanzapine on the weight of patients with bipolar disorder. Data Sources: EMBASE, Medline, and PsycINFO were searched using the keywords olanzapine AND (bipolar OR acute mania) in conjunction with (weight gain OR weight increase) (last search: October 2010, with no restrictions on dates of publication). English language was used as a restriction. Study Selection: The search identified 110 articles for review. The inclusion criteria for the chosen studies were a diagnosis of bipolar disorder, the presence of an olanzapine monotherapy group, a comparator placebo or monotherapy group, and mean weight gain and/or incidences of weight gain data. This process identified 13 studies for inclusion. Data Extraction: The primary outcome measure was the mean weight change between olanzapine monotherapy and comparator monotherapy, reported in kilograms. Standard deviation was extracted directly from studies when possible and imputed for 3 studies. The secondary outcome measure was the reported incidences of ≥ 7% weight gain. Data Synthesis: The mean difference in weight gain was calculated for the continuous data of the primary outcome. Olanzapine monotherapy was associated with more weight gain when compared to placebo (mean difference = 2.10 kg; 95% CI, 1.16–3.05; P < .001) and other bipolar monotherapy (mean difference = 1.34 kg; 95% CI, 0.95–1.72; P < .001). Odds ratio analysis of the dichotomous secondary outcome also showed more weight gain with olanzapine monotherapy compared to placebo (odds ratio [OR] = 10.12; 95% CI, 1.93– 53.14; P = .006) and other bipolar monotherapy (OR = 2.09; 95% CI, 1.27–3.44; P = .004). Conclusions: Currently available data suggest that olanzapine is associated with significant weight gain in bipolar patients. Issues related to side effect profiles and their impact on treatment compliance and physical health outcomes need to be considered when selecting pharmacotherapy.
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Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler's method. The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter. Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.
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Background Studies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation. Methods The Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regression Results We found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population. Conclusions This study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men.
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Despite recent evidence that patients with bipolar disorder are at increased risk of premature mortality resulting from general medical disorders, there has been no systematic review of published studies. The authors reviewed the literature to determine whether there is evidence of increased risk of mortality from general medical causes among patients with bipolar spectrum disorders. MEDLINE was searched from 1959 to 2007 with a focus on bipolar disorder and medical mortality. Published studies in English with more than 100 patients were included. Seventeen studies were identified involving 331,000 patients with bipolar disorder, affective psychosis, affective disorder severe enough to require inpatient psychiatric care or treatment with lithium, or schizoaffective disorder (that is, bipolar spectrum disorders) meeting the inclusion criteria. Compared with age- and sex-matched control samples without mental illness in the general population, mortality ratios for death from natural causes and from specific general medical conditions, such as cardiovascular, respiratory, cerebrovascular, and endocrine disorders, were significantly higher among patients with bipolar spectrum disorders in most studies. This finding was more consistent in larger studies with more than 2,500 patients with bipolar spectrum disorders. Cumulatively, cardiovascular disorder appeared to be the most consistent cause of excess mortality in larger studies. The available evidence suggests that bipolar spectrum disorders are associated with increased premature mortality secondary to general medical illnesses. Unhealthy lifestyle, biological factors, adverse pharmacologic effects, and disparities in health care are possible underlying causes for this excess mortality.
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Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia and lipid dysregulation in patients treated with second-generation (or atypical) antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. This comprehensive literature review considers the evidence for and against an association between glucose or lipid dysregulation and eight separate second-generation antipsychotics currently available in the US and/or Europe, specifically clozapine, olanzapine, risperi-done, quetiapine, zotepine, amisulpride, ziprasidone and aripiprazole. This review also includes an assessment of the potential contributory role of treatment-induced weight gain in conferring risk for hyperglycaemia and dyslipidaemia during treatment with different antipsychotic medications.
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We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials in acute bipolar mania to summarize available data on drug treatment of mania. We included trials of medications licensed in the USA or UK for the treatment of any phase of bipolar disorder. Outcomes investigated were changes in mania scores, attrition, extrapyramidal effects and weight change. Data were combined through meta-analyses. We included 13 studies (involving 3,089 subjects) and identified 2 studies for each of the following medications: carbamazepine, haloperidol, lithium, olanzapine, quetiapine, risperidone, valproate semisodium and aripiprazole. All drugs showed significant benefit compared with placebo for reduction in mania scores. Compared with placebo, for all antipsychotics pooled, response to treatment (> or =50% reduction in Young Mania Rating Scale scores) was increased more than 1.7 times [relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.54, 1.96]; for all mood stabilizers pooled, response to treatment was doubled (RR 2.01, 95% CI = 1.66, 2.43). Overall withdrawals were 34% fewer (24-43%) with antipsychotics, and 26% fewer (10-39%) with mood stabilizers. However, for carbamazepine, aripiprazole and lithium an increase in risk of withdrawal could not be excluded. Small but significant increases in extrapyramidal side effects occurred with risperidone and aripiprazole. Antipsychotics and mood stabilizers are significantly more effective than placebo for the treatment of acute mania. Their effect sizes are similar. Small differences between effect sizes may be due to differences in the patients included in the studies or to chance. Carbamazepine and lithium may be more poorly tolerated, and antipsychotics cause more extrapyramidal side effects.
Article
Background Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention. Methods We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95000 individuals at low average risk, 660000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17000 individuals at high average risk, 43 000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period. Findings in the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year, p=0.0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0.18% vs 0.23% per year, p<0.0001). The net effect on stroke was not significant (0.20% vs 0.21% per year, p=0.4: haernorrhagic stroke 0.04% vs 0.03%, p=0.05; other stroke 0.16% vs 0.18% per year, p=0.08). Vascular mortality did not differ significantly (0.19% vs 0.19% per year, p=0.7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0.10% vs 0.07% per year, p<0.0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6.7% vs 8.2% per year, p<0.0001), with a non-significant increase in haernorrhagic stroke but reductions of about a fifth in total stroke (2.08% vs 2.54% per year, p=0.002) and in coronary events (4.3% vs 5.3% per year, p<0.0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women. Interpretation In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, and the European Community Biomed Programme.
Article
To perform a detailed, qualitative review of existing literature on the co-occurrence of bipolar disorder and metabolic syndrome, the impact of metabolic dysregulation on patients with bipolar disorder, and treatment considerations, with a focus on bipolar depression. Searches of the PubMed database (October 23, 2012) and Cochrane Library (September 20, 2013) were conducted for English-language articles published from January 1980 onward containing the keywords bipolar AND metabolic, weight, obesity, diabetes, dyslipidemia, OR hypertension in the title or abstract. The searches yielded 1,817 citations from which case reports, conference abstracts, and pediatric studies were excluded. Abstracts and titles were evaluated for relevance to the stated objectives. Full texts of 176 articles were obtained for further evaluation; additional articles were identified from reference lists. Metabolic risk factors are highly prevalent yet undertreated in patients with bipolar disorder. Putative factors accounting for the link between bipolar disorder and metabolic syndrome include behavioral/phenomenological features, shared neurobiologic abnormalities, and adverse effects of psychotropic medications. A comprehensive assessment of metabolic risk and regular monitoring of body mass index, waist circumference, lipid profile, and plasma glucose are important for patients with bipolar disorder. Management strategies for the bipolar patient with metabolic risk factors include use of bipolar disorder medications with better metabolic profiles, lifestyle interventions, and adjunctive pharmacotherapy for dyslipidemia, hypertension, and/or hyperglycemia. Adequate management of metabolic syndrome may improve clinical outcomes in patients with bipolar disorder, as well as prevent adverse cardiovascular events and the development of diabetes.
Article
Bipolar Disorders (BD) are currently regarded as a multidimensional disease involving both psychological and physical determinants. If mood dimension and thymic instability have usually been considered as the « core » aspect of bipolar disorders, it's crucial to note that somatic problems frequently occur in BD, deeply worsening the prognosis of this affection. Indeed, comorbid somatic illnesses of bipolar disorder are mainly represented by cardiovascular and metabolic disorders, which are shortening life expectancy by 25 to 30 years as compared to the general population. In this review, the authors examine epidemiological data about this comorbidity, then they attempt to provide etiologic and physiopathologic hypotheses about the links between bipolar disorders and metabolic diseases. Despite the absence of strong scientific explanation for this link, its existence highlights the need for more integrated care and interdisciplinary collaboration in order to improve patients'outcome. Copyright © 2012 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.
Article
In secondary prevention among a wide range of patients who have survived a prior occlusive vascular event, as well as during acute myocardial infarction and acute occlusive stroke, aspirin produces statistically significant and clinically important reductions in the risk of subsequent myocardial infarction, stroke, and vascular death. In primary prevention, aspirin reduces risk of a first myocardial infarction, but the data on stroke and vascular deaths remain inconclusive. In addition, the average absolute risk of subjects randomized in the primary prevention trials was so low that it is not possible to get reliable estimates of the benefit-to-risk ratio in primary prevention in subjects at moderate risk. Until the results of ongoing trials are available, nobody would disagree that a nonfatal myocardial infarction or stroke is more likely to be disabling than a nonfatal bleed. Thus, in primary prevention at present, the appropriate and judicious use of aspirin by clinicians based on individual clinical judgments that weigh their absolute benefits against the absolute risks of the drug, will avoid premature morbidity and possibly, mortality.
Article
Importance: Bipolar disorder is associated with premature mortality, but the specific causes and underlying pathways are unclear. Objective: To examine the physical health effects of bipolar disorder using outpatient and inpatient data for a national population. Design, setting, and participants: National cohort study of 6,587,036 Swedish adults, including 6618 with bipolar disorder. Main outcomes and measures: Physical comorbidities diagnosed in any outpatient or inpatient setting nationwide and mortality (January 1, 2003, through December 31, 2009). Results: Women and men with bipolar disorder died 9.0 and 8.5 years earlier on average than the rest of the population, respectively. All-cause mortality was increased 2-fold among women (adjusted hazard ratio [aHR], 2.34; 95% CI, 2.16-2.53) and men (aHR, 2.03; 95% CI, 1.85-2.23) with bipolar disorder, compared with the rest of the population. Patients with bipolar disorder had increased mortality from cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide for both women and men and cancer for women only. Suicide risk was 10-fold among women (aHR, 10.37; 95% CI, 7.36-14.60) and 8-fold among men (aHR, 8.09; 95% CI, 5.98-10.95) with bipolar disorder, compared with the rest of the population. Substance use disorders contributed only modestly to these findings. The association between bipolar disorder and mortality from chronic diseases (ischemic heart disease, diabetes, COPD, or cancer) was weaker among persons with a prior diagnosis of these conditions (aHR, 1.40; 95% CI, 1.26-1.56) than among those without a prior diagnosis (aHR, 2.38; 95% CI, 1.95-2.90; P(interaction) = .01). Conclusions and relevance: In this large national cohort study, patients with bipolar disorder died prematurely from multiple causes, including cardiovascular disease, diabetes, COPD, influenza or pneumonia, unintentional injuries, and suicide. However, chronic disease mortality among those with more timely medical diagnosis approached that of the general population, suggesting that better provision of primary medical care may effectively reduce premature mortality among persons with bipolar disorder.
Article
Background: Although transient psychotic disorders are currently classified as a category separate from schizophrenia (SZ) and affective disorders, their distinctive features remain uncertain. This study examines the family psychiatric morbidity of the ICD-10 category of 'acute and transient psychotic disorders' (ATPDs), pointing out differences from SZ and bipolar disorder (BD). Method: From a cohort of 2.5 million persons, we identified all patients enrolled in the Danish Psychiatric Register who were ever admitted with ATPDs (n=2537), SZ (n = 10639) and BD disorder (n=5292) between 1996 and 2008. The relative risk (RR) of ATPDs, SZ and BD associated with psychiatric morbidity in first-degree relatives (FDRs) was calculated as the incidence rate ratio using Poisson regression. Results: The RR of ATPDs [1.93, 95% confidence interval (CI) 1.76-2.11] was higher if patients with ATPDs had at least one FDR admitted with any mental disorder than patients without family psychiatric antecedents. An additional risk arose if they had FDRs admitted not only with ATPDs (RR 1.60, 95% CI 1.33-1.92) but also with SZ (RR 2.06, 95% CI 1.70-2.50) and/or BD (RR 1.55, 95% CI 1.23-1.96). Despite some overlap, the risk of SZ (RR 2.80, 95% CI 2.58-3.04) and BD (RR 3.68, 95% CI 3.29-4.12) was markedly higher if patients with SZ and BD had FDRs admitted with the same condition. Conclusions: These findings suggest that family psychiatric predisposition has a relatively modest impact on ATPDs and argue against a sharp differentiation of ATPDs from SZ and BD.
Article
Background: Olanzapine is prescribed for a number of psychiatric disorders, including schizophrenia, bipolar mania, and unipolar and bipolar depression. Olanzapine treatment is associated with tolerability issues such as metabolic adverse effects (e.g. weight gain, increase in blood glucose, triglycerides and total cholesterol levels), extrapyramidal symptoms [EPS] (e.g. parkinsonism, akathisia, tardive dyskinesia) and sedative adverse effects. Metabolic issues lead to some long-term consequences, which include cardiovascular diseases (CVD) and type 2 diabetes mellitus, and these complications cause high rates of mortality and morbidity among patients with severe mental illnesses. The expanded indications of olanzapine in psychiatry suggest a need to investigate whether there is a difference in the incidence and severity of adverse effects related to category diagnosis. Are the adverse effects expressed differently according to phenotype? Unfortunately, there are no reported studies that investigated these differences in adverse effects associated with olanzapine treatment in psychiatric patients with different phenotypes. Objective: The aim of the present meta-analysis is to separately examine olanzapine-induced cardiometabolic adverse effects and EPS in patients with schizophrenia and affective disorders. Data Sources: A search of computerized literature databases PsycINFO (1967–2010), PubMed (MEDLINE), EMBASE (1980–2010) and the clinicaltrials.gov website for randomized clinical trials was conducted. A manual search of reference lists of published review articles was carried out to gather further data. Study Selection: Randomized controlled trials were included in our study if (i) they assessed olanzapine adverse effects (metabolic or extrapyramidal) in adult patients with schizophrenia or affective disorders; and (ii) they administered oral olanzapine as monotherapy during study. Data Extraction: Two reviewers independently screened abstracts for choosing articles and one reviewer extracted relevant data on the basis of predetermined exclusion and inclusion criteria. It should be mentioned that for the affective disorders group we could only find articles related to bipolar disorder. Data Synthesis: Thirty-three studies (4831 patients) that address olanzapine monotherapy treatment of adults with schizophrenia or bipolar disorder were included in the analysis. The primary outcomes were metabolic adverse effects (changes in weight, blood glucose, low-density lipoprotein, total cholesterol and triglyceride levels). The secondary outcomes of our study were assessing the incidence of some EPS (parkinsonism, akathisia and use of antiparkinson medication). The tolerability outcomes were calculated separately for the schizophrenia and bipolar disorder groups and were combined in a meta-analysis. Tolerability outcomes show that olanzapine contributes to weight gain and elevates blood triglycerides, glucose and total cholesterol levels in both schizophrenia and bipolar disorder patients. However, olanzapine treatment produced significantly more weight gain in schizophrenia patients than in bipolar disorder patients. In addition, increases in blood glucose, total cholesterol and triglyceride levels were higher in the schizophrenia group compared with the bipolar disorder group, even though these differences were not statistically significant. Based on our results, the incidence of parkinsonism was significantly higher in the schizophrenia group than in the bipolar disorder group. Subgroup analysis and logistic regression were used to assess the influence of treatment duration, dose, industry sponsorship, age and sex ratio on tolerability outcome. Conclusions: Our results suggest that schizophrenia patients may be more vulnerable to olanzapine-induced weight gain. The findings may be explained by considering the fact that in addition to genetic disposition for metabolic syndrome in schizophrenia patients, they have an especially high incidence of lifestyle risk factors for CVD, such as poor diet, lack of exercise, stress and smoking. It might be that an antipsychotic induces severity of adverse effect according to the phenotype.
Article
Objective: The weight impact produced by the atypical antipsychotic olanzapine has been explored in meta-analyses focusing on patients with schizophrenia. However, outcomes identified for schizophrenia patients cannot always be generalized to patients with bipolar disorder. This study aims to quantitatively estimate the impact of olanzapine on the weight of patients with bipolar disorder. Data sources: EMBASE, Medline, and PsycINFO were searched using the keywords olanzapine AND (bipolar OR acute mania) in conjunction with (weight gain OR weight increase) (last search: October 2010, with no restrictions on dates of publication). English language was used as a restriction. Study selection: The search identified 110 articles for review. The inclusion criteria for the chosen studies were a diagnosis of bipolar disorder, the presence of an olanzapine monotherapy group, a comparator placebo or monotherapy group, and mean weight gain and/or incidences of weight gain data. This process identified 13 studies for inclusion. Data extraction: The primary outcome measure was the mean weight change between olanzapine monotherapy and comparator monotherapy, reported in kilograms. Standard deviation was extracted directly from studies when possible and imputed for 3 studies. The secondary outcome measure was the reported incidences of ≥ 7% weight gain. Data synthesis: The mean difference in weight gain was calculated for the continuous data of the primary outcome. Olanzapine monotherapy was associated with more weight gain when compared to placebo (mean difference = 2.10 kg; 95% CI, 1.16-3.05; P < .001) and other bipolar monotherapy (mean difference = 1.34 kg; 95% CI, 0.95-1.72; P < .001). Odds ratio analysis of the dichotomous secondary outcome also showed more weight gain with olanzapine monotherapy compared to placebo (odds ratio [OR] = 10.12; 95% CI, 1.93-53.14; P = .006) and other bipolar monotherapy (OR = 2.09; 95% CI, 1.27-3.44; P = .004). Conclusions: Currently available data suggest that olanzapine is associated with significant weight gain in bipolar patients. Issues related to side effect profiles and their impact on treatment compliance and physical health outcomes need to be considered when selecting pharmacotherapy.
Article
Depressive symptoms and episodes dominate the course of bipolar disorder. However, the therapeutic armamentarium for bipolar depression is limited. Recent evidence points to the efficacy of second generation antipsychotics (SGAs) for the treatment of bipolar depression. We conducted a systematic review and meta-analysis of the efficacy and safety of SGAs (randomized, double-blind, placebo-controlled trials; used in monotherapy) in the treatment of adult patients with bipolar depression. Publication bias was corrected for by performing similar searches using the clinical trials register of the respective pharmaceutical companies, the Cochrane Database and ClinicalTrials.gov. Seven published papers were identified on the use of aripiprazole, olanzapine and quetiapine. Internal validity of the trials was fairly good, external validity only moderate. Different outcome measures of efficacy and safety were assessed. When the individual trials were looked at, quetiapine and to a lesser extent olanzapine demonstrated significant improvement in MADRS (Montgomery-Åsberg Depression Rating Scale) total scores. This was not demonstrated for aripiprazole. Efficacy was hampered by adverse events, such as weight gain, akathisia and somnolence/sedation. Both clinical heterogeneity of the included trials and statistical heterogeneity of the meta-analytic data were considerable. The number of quetiapine trials was disproportionate to the number of trials of aripiprazole and olanzapine. Further research is needed to assess differential efficacy of the different SGAs and their use in clinical practice.
Article
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.
Article
The role of serum lipids [total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] in the pathophysiology of mood disorders is not clear. The aim of this study was to determine lipid profiles in patients with affective disorders. The study included medication-free female subjects (41 patients with bipolar disorder, 22 in a manic and 19 in a depressive phase), 34 patients with major depression, and 50 healthy controls. Serum lipid levels were determined using standard laboratory tests. All patients had significantly lower HDL-C values than control subjects. Increased TG levels were found in patients with bipolar disorder compared with healthy subjects. The changes in lipid profiles persisted when data were adjusted for age, smoking and menopausal status. The results revealed no differences in cholesterol and LDL-C levels and body mass index, but significant differences in the ratios of cholesterol/HDL-C and LDL-C/HDL-C (atherogenic index) among groups. Our results suggest that low HDL-C levels and a high atherogenic index might be a hallmark of affective disorders. Since low HDL-C levels could be a risk factor for the development of coronary heart disease, further investigation of lipid metabolism in affective disorders is warranted.
Article
Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention. We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95,000 individuals at low average risk, 660,000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17,000 individuals at high average risk, 43,000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period. In the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year, p=0.0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0.18%vs 0.23% per year, p<0.0001). The net effect on stroke was not significant (0.20%vs 0.21% per year, p=0.4: haemorrhagic stroke 0.04%vs 0.03%, p=0.05; other stroke 0.16%vs 0.18% per year, p=0.08). Vascular mortality did not differ significantly (0.19%vs 0.19% per year, p=0.7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0.10%vs 0.07% per year, p<0.0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6.7%vs 8.2% per year, p<0.0001), with a non-significant increase in haemorrhagic stroke but reductions of about a fifth in total stroke (2.08%vs 2.54% per year, p=0.002) and in coronary events (4.3%vs 5.3% per year, p<0.0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women. In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress. UK Medical Research Council, British Heart Foundation, Cancer Research UK, and the European Community Biomed Programme.
Article
Treatment of coexisting medical comorbidities may reduce the risk of adverse outcomes among patients with bipolar disorder. We determined the prevalence of general medical conditions in a population-based sample of patients diagnosed with bipolar disorder in the Veterans Administration (VA). We conducted a cross-sectional study of patients (n = 4310) diagnosed with bipolar disorder in fiscal year 2001 receiving care at VA facilities located within the mid-Atlantic region. General medical conditions were assessed using ICD-9 codes, and we compared the prevalence of each condition in our bipolar sample with national data on the VA patient population. The mean age was 53 (SD = 13), 10% were women, and 12% African-American. The mean age of the VA national patient population was higher (58 years). The most prevalent conditions among patients with bipolar disorder included cardiovascular (e.g. hypertension, 35%), endocrine (e.g. hyperlipidemia, 23%; diabetes, 17%), and alcohol use disorder (25%). When compared with national data, the prevalence of diabetes was higher in the bipolar cohort than in the national cohort (17.2% versus 15.6%; p = 0.0035). Hepatitis C was more common in the bipolar group than the national cohort (5.9% versus 1.1%; p < 0.001). Lower back pain (15.4% versus 10.6%; p < 0.0001) and pulmonary conditions (e.g. COPD: 10.6% versus 9.4%; p = 0.005) were also more prevalent among the bipolar cohort than the VA national cohort. Individuals with bipolar disorder possess a substantial burden of general medical comorbidity, and are occurring at an earlier age than in the general VA patient population, suggesting the need for earlier detection and treatment for patients with bipolar disorder.
Article
Patients with bipolar disorder may be at greater risk for overweight and obesity than individuals in the general population. This risk may be due to the illness itself, to mediating factors (diet, life style) and/or to medications used to treat the disorder. This investigation explores the association between body weight and bipolar illness in drug-naïve patients. Weight and height were retrospectively obtained from 76 clinical charts of drug-naïve patients with bipolar disorder (DSM-IV-TR). A reference group for comparison was then selected from another psychiatric population (65 patients with obsessive-compulsive disorder) and investigated with the same methodology to estimate their BMI. A second focus was to examine the differences in baseline demographic and clinical characteristics between overweight and non-overweight bipolar patients. A total of 40.8% of the patients with bipolar disorder met criteria for obesity or overweight with significant difference in comparison with obsessive-compulsive patients (10.8%). The highest proportions of depression at index episode were in the overweight group (83.3%) with significant difference with the non-overweight patients (58.1%). Retrospective study. Weight measurement not in euthymic period. Overweight is significantly more prevalent in drug-naïve patients with bipolar disorder than in another drug-naïve psychiatric patients (OCD). In agreement with previous studies, the number of patients experiencing a depressive episode was significantly higher in the overweight than in the non-overweight group. These results suggest that the prevalence of overweight in bipolar patients is also influenced by the illness itself or mediating factors such as diet and life style than by pharmacologic treatment.
Bipolar disorders and somatic comorbidities: a focus on metabolic syndrome, diabetes and cardiovascular disease
  • J C Chauvet-Gelinier
  • I Gaubil
  • A Kaladjian
  • B Bonin
Chauvet-Gelinier, J.C., Gaubil, I., Kaladjian, A., Bonin, B., 2012. Bipolar disorders and somatic comorbidities: a focus on metabolic syndrome, diabetes and cardiovascular disease. Encephale 38 (Suppl. 4), S167-S172.
Bipolar disorders and somatic comorbidities: a focus on metabolic syndrome, diabetes and cardiovascular disease
  • Chauvet-Gelinier
Comparing tolerability of olanzapine in schizophrenia and affective disorders: a meta-analysis
  • Moteshafi
Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review
  • Newcomer