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Letter to the Editor
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Because this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.
Patients with severe mental disorders have increased mortality rates compared with the general population. The leading cause of death for individuals with psychotic illnesses or bipolar disorder is cardiovascular disease (CVD), which is often the result of patients' health problems associated with their psychiatric disorders, including, but not limited to, obesity, metabolic syndrome, and diabetes. Such problems occur more often and have worse outcomes in patients with serious mental illness than the general population because of a combination of factors such as inadequate access to quality care, poor lifestyle choices, and the association between some antipsychotic medications and weight gain. Coordinated somatic and psychiatric treatment, weight-neutral or weight-reducing pharmaceuticals, and behavioral weight management programs may help lessen the burden of CVD in the mental health population.
Objective: To review extant literature implicating inflammation in the pathophysiology of bipolar disorder. Furthermore, we review evidence regarding the anti-inflammatory actions of mood-stabilizing medication, the putative reciprocal association of inflammation with behavioral parameters and medical burden in bipolar disorder, and the potential role of anti-inflammatory agents in the treatment of bipolar disorder.
Data Sources: MEDLINE and PubMed searches were conducted of English-language articles published from 1950 to April 2008 using the search terms bipolar disorder, manic, or mania, cross-referenced with inflammation, inflammatory, interleukin, cytokine, C-reactive protein, or tumor necrosis factor. The search, which was conducted most recently on August 20, 2008, was supplemented by manually reviewing reference lists from the identified publications.
Study Selection: Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality.
Data Extraction: Studies were reviewed for statistical comparisons of cytokines among persons with and without bipolar disorder, during symptomatic and non-symptomatic intervals and before and after pharmacologic treatment. Significant and nonsignificant findings were tabulated.
Data Synthesis: Available evidence indicates that bipolar disorder and inflammation are linked through shared genetic polymorphisms and gene expression as well as altered cytokine levels during symptomatic (i.e., mania and depression) and asymptomatic intervals. However, results are inconsistent. Several conventional mood stabilizers have anti-inflammatory properties. The cyclooxygenase-2-selective anti-inflammatory celecoxib may offer antidepressant effects. Inflammation is closely linked with behavioral parameters such as exercise, sleep, alcohol abuse, and smoking, as well as with medical comorbidities including coronary artery disease, obesity and insulin resistance, osteoporosis, and pain. Methodological limitations precluding definitive conclusions are heterogeneity in sample composition, cytokine assessment procedures, and treatment regimens. The inclusion of multiple ethnic groups introduces another source of variability but also increases the generalizability of study findings.
Conclusion:Inflammation appears relevant to bipolar disorder across several important domains. Further research is warranted to parse the reciprocal associations between inflammation and symptoms, comorbidities, and treatments in bipolar disorder. Studies of this topic among youth are needed and may best serve this purpose.
Received June 29, 2008; accepted Aug. 22, 2008. From the Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pa. (Dr. Goldstein); the Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio (Dr. Kemp); the Mood Disorders Psychopharmacology Unit, University Health Network, and the Institute of Medical Science, University of Toronto, Ontario, Canada (Dr. McIntyre and Ms. Soczynska); and the Departments of Psychiatry and Pharmacology, University of Toronto, Ontario, Canada (Dr. McIntyre).
Dr. Kemp has received grant/research support from the National Institutes of Health and Takeda; has received honoraria from Servier; has been a consultant for Abbott, Bristol-Myers Squibb, and Wyeth; and has received other financial or material support from Organon. Dr. McIntyre has received grant/research support from the Stanley Medical Research Institute, NARSAD, and Eli Lilly; has been a member of the speakers/advisory boards for AstraZeneca, Bristol-Myers Squibb, the France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, and Shire; and has received other financial or material support from AstraZeneca, Bristol-Myers Squibb, the France Foundation, 13CME, Solvay/Wyeth, and Physicians Postgraduate Press. Dr. Goldstein and Ms. Soczynska report no financial or other relationship relevant to the subject of this article.
Corresponding author and reprints: Benjamin I. Goldstein, M.D., Ph.D., Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O' Hara Street, Pittsburgh, PA 16213 (e-mail: [email protected]).
Background: Approximately 15% of patients with schizophrenia also meet DSM-IV criteria for obsessive-compulsive disorder (OCD) at some point in their illness, a rate considerably higher than in the general population. This study examined aripiprazole treatment of patients with comorbid schizophrenia and obsessive-compulsive symptoms (OCS) that did not meet full criteria for OCD.
Method: Physically healthy adults aged 18 to 65 years with DSM-IV schizophrenia and a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (YBOCS) were eligible to participate in this 6-week, open-label, flexible-dose trial of aripiprazole monotherapy. Patients currently taking another antipsychotic medication were concurrently down-titrated from their current antipsychotic and up-titrated with aripiprazole, starting with 15 mg/day. Coadministration of the 2 medications lasted from 7 to 14 days, until a stable therapeutic dose of 10 to 30 mg/day was reached. Subjects were recruited into the study, which was conducted at the Schizophrenia Clinic of Stanford University School of Medicine, between January 2005 and December 2006.
Results: Of 15 eligible patients, 7 completed the trial. All 7 had at least minimal improvement on the YBOCS, the Clinical Global Impressions (CGI) scale, and the Positive and Negative Syndrome Scale (PANSS). At week 6, the mean CGI-Improvement scale score was 2.3 (much improved). Mean PANSS scores decreased from 75 to 56, a mean decrease of 21%, (p < .05). On the YBOCS, 6 of 7 completers showed a change of greater than 35% from baseline to week 6.
Conclusion: These results suggest that aripiprazole monotherapy can modestly improve the outcome for some schizophrenia patients with obsessive-compulsive symptoms. Further studies with aripiprazole under controlled conditions are indicated for this population of patients. Overall, even modest improvement in global functioning due to an improvement in an OCS component may be clinically meaningful for this difficult-to-treat subset of schizophrenia patients.
Background: Primary care physicians, rather than psychiatrists, prescribe a majority of psychotropic medications in the United States. However, past research has shown significant differences in psychopharmacologic treatment practices of these 2 groups of physicians. The objective of this study was to compare patient characteristics and treatment patterns of adults in the United States treated with antidepressant medications by psychiatrists and other medical providers.
Method: Data from the National Comorbidity Survey Replication (February 2001-April 2003) were used to compare characteristics of adults (aged >= 18 years) prescribed antidepressants by psychiatrists (N = 255) or other medical providers (N = 673). The treatment groups were also compared with respect to presenting problem, antidepressant type and dose, and continuity of treatment.
Results: Approximately 1 in 10 adults (10.5%) were treated with an antidepressant in the past year, usually by a general medical provider (73.6%). Compared with those treated by psychiatrists, adults treated by general medical providers were significantly more likely to be at least 65 years of age and to reside in a nonurban area. By contrast, those treated by psychiatrists were significantly more likely to be male, to report significant distress, to present with serious mood or anxiety symptoms, and to meet DSM-IV criteria for mood and anxiety disorders. Individuals treated by psychiatrists typically received higher doses of medications, were less likely to stop the medication before 30 days, and were more likely to continue 90 days or longer.
Conclusions: Most adults treated with antidepressants receive the medication from general medical providers. In comparison with adults treated by psychiatrists, those treated by general medical providers are less likely to meet the criteria for mood or anxiety disorders or to continue medication beyond the first month. Quality improvement initiatives in general medical settings should focus on better targeting and continuity of antidepressant medications.
Objectives: To present nationally representative findings on prevalence, sociodemographic correlates, disability, and comorbidity of narcissistic personality disorder (NPD) among men and women.
Method: Face-to-face interviews with 34,653 adults participating in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions conducted between 2004 and 2005 in the United States.
Results: Prevalence of lifetime NPD was 6.2%, with rates greater for men (7.7%) than for women (4.8%). NPD was significantly more prevalent among black men and women and Hispanic women, younger adults, and separated/divorced/widowed and never married adults. NPD was associated with mental disability among men but not women. High co-occurrence rates of substance use, mood, and anxiety disorders and other personality disorders were observed. With additional comorbidity controlled for, associations with bipolar I disorder, posttraumatic stress disorder, and schizotypal and borderline personality disorders remained significant, but weakened, among men and women. Similar associations were observed between NPD and specific phobia, generalized anxiety disorder, and bipolar II disorder among women and between NPD and alcohol abuse, alcohol dependence, drug dependence, and histrionic and obsessive-compulsive personality disorders among men. Dysthymic disorder was significantly and negatively associated with NPD.
Conclusion: NPD is a prevalent personality disorder in the general U.S. population and is associated with considerable disability among men, whose rates exceed those of women. NPD may not be as stable as previously recognized or described in the DSM-IV. The results highlight the need for further research from numerous perspectives to identify the unique and common genetic and environmental factors underlying the disorder-specific associations with NPD observed in this study.
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