Vasculopathy related to manic/hypomanic symptom burden and first-generation antipsychotics in a sub-sample from the collaborative depression study.

BACKGROUND: Mood disorders substantially increase the risk of cardiovascular disease, though the mechanisms are unclear. We assessed for a dose-dependent relationship between course of illness or treatment with vasculopathy in a well-characterized cohort. METHODS: Participants with mood disorders were recruited for the National Institute of Mental Health Collaborative Depression Study (CDS) and followed prospectively. A cross-sectional metabolic and vascular function evaluation was performed on a sub-sample near completion after a mean follow-up of 27 years. RESULTS: A total of 35 participants from the University of Iowa (33) and Washington University (2) sites of the CDS consented to a metabolic and vascular function assessment at the Iowa site. In multivariate linear regression, controlling for age, gender, and smoking, manic/hypomanic, but not depressive, symptom burden was associated with lower flow-mediated dilation. Cumulative exposure to antipsychotics and mood stabilizers was associated with elevated augmentation pressure and mean aortic systolic blood pressure. This appeared specifically related to first-generation antipsychotic exposure and mediated by increases in brachial systolic pressure. Although second-generation antipsychotics were associated with dyslipidemia and insulin resistance, they were not associated with vasculopathy. CONCLUSIONS: These results provide evidence that chronicity of mood symptoms contribute to vasculopathy in a dose-dependent fashion. Patients with more manic/hypomanic symptoms had poorer endothelial function. First-generation antipsychotic exposure was associated with arterial stiffness, evidenced by higher augmentation pressure, perhaps secondary to elevated blood pressure. Vascular phenotyping methods may provide a promising means of elucidating the mechanisms linking mood disorders to vascular disease.

Factors associated with the prescribing of olanzapine, quetiapine, and risperidone in patients with bipolar and related affective disorders.

STUDY OBJECTIVE: To identify the factors associated with newly prescribed, first-line, second-generation antipsychotics (SgAs) associated with weight gain-olanzapine, risperidone, and quetiapine. DESIGN: Retrospective medical record review. SETTING: Outpatient and inpatient psychiatry services at a tertiary care, academic medical center. PATIENTS: Three hundred forty consecutive adults who had major depressive disorder with psychotic features, bipolar I, bipolar II, bipolar not otherwise specified, or schizoaffective disorder over two time periods (August 30-October 30, 2009, and April 1-May 31, 2010). MEASUREMENTS AND MAIN RESULTS: Clinical and sociodemographic variables associated with newly prescribed olanzapine, risperidone, and quetiapine were identified by using univariate and multivariate logistic regression. Several clinical factors were individually associated with initiation of these SgAs: mania (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.8, p=0.02), psychosis (OR 3.3, 95% CI 1.5-6.9, p=0.002), and inpatient treatment (OR 3.8, 95% CI 1.8-7.9, p=0.0005). Prevalent use of lithium (OR 0.3, 95% CI 0.1-0.9, p=0.03) and being married (OR 0.3, 95% CI 0.1-0.8, p=0.02) were inversely associated with new use of an SgA. Mania, psychosis, married status, and lithium use remained independently associated on multivariate analysis. Factors related to metabolic or vascular risk were not associated with SgA initiation. CONCLUSION: Psychiatric clinicians were influenced heavily by clinical features related to mental status and acuity when determining whether to prescribe SgAs. However, factors related to vascular risk were not associated. Future observational studies should consider current clinical status as an important factor in determining propensity to receive antipsychotics or other short-term treatments for bipolar and related disorders.

Cardiovascular morbidity and mortality in bipolar disorder.

BACKGROUND: There has been considerable interest in the elevated risk of cardiovascular disease associated with serious mental illness. Although the contemporary literature has paid much attention to major depression and schizophrenia, focus on the risk of cardiovascular mortality for patients with bipolar disorder has been more limited, despite some interest in the historical literature. METHODS: We reviewed the historical and contemporary literature related to cardiovascular morbidity and mortality in bipolar disorder. RESULTS: In studies that specifically assess cardiovascular mortality, bipolar disorder has been associated with a near doubling of risk when compared with general population estimates. This may be explained by the elevated burden of cardiovascular risk factors found in this population. These findings predate modern treatments for bipolar disorder, which may further influence cardiovascular risk. CONCLUSIONS: Given the substantial risk of cardiovascular disease, rigorous assessment of cardiovascular risk is warranted for patients with bipolar disorder. Modifiable risk factors should be treated when identified. Further research is warranted to study mechanisms by which this elevated risk for cardiovascular disease are mediated and to identify systems for effective delivery of integrated medical and psychiatric care for individuals with bipolar disorder.