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ABSTRACT: Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl- D-aspartate-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore, we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery.
We recruited subjects aged 60 years and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10 mg/d for 1 week, then 10 mg twice daily) or placebo, for 12 weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes.
Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12 week randomized controlled trial. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome.
Memantine was not associated with superior affective or functional outcome compared with placebo in medically rehabilitating older adults with depressive and apathy symptoms.
International Journal of Geriatric Psychiatry 12/2011; 27(9):974-80. · 2.42 Impact Factor
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ABSTRACT: The benefits of some second-generation antipsychotics (SGAs) must be weighed against the increased risk for diabetes mellitus. This study examines whether the association between SGAs and diabetes differs by dose.
Patients were ≥18 years of age from three US healthcare systems and exposed to an SGA for ≥45 days between November 1, 2002 and March 31, 2005. Patients had no evidence of diabetes before index date and no previous antipsychotic prescription filled within 3 months before index date.49,946 patients were exposed to SGAs during the study period. Person-time exposed to antipsychotic dose (categorized by tertiles for each drug) was calculated. Newly treated diabetes was identified using pharmacy data to determine patients exposed to anti-diabetic therapies. Adjusted hazard ratios for diabetes across dose tertiles of SGA were calculated using the lowest dose tertile as reference.
Olanzapine exhibited a dose-dependent relationship for risk for diabetes, with elevated and progressive risk across intermediate (diabetes rate per 100 person-years = 1.9; adjusted Hazard Ratio (HR), 1.7, 95% confidence interval (CI), 1.0-3.1) and top tertile doses (diabetes rate per 100 person-years = 2.7; adjusted HR, 2.5, 95% CI, 1.4-4.5). Quetiapine and risperidone exhibited elevated risk at top dose tertile with no evidence of increased risk at intermediate dose tertile. Unlike olanzapine, quetiapine, and risperidone, neither aripiprazole nor ziprasidone were associated with risk of diabetes at any dose tertile.
In this large multi-site epidemiologic study, within each drug-specific stratum, the risk of diabetes for persons exposed to olanzapine, risperidone, and quetiapine was dose-dependent and elevated at therapeutic doses. In contrast, in aripiprazole-specific and ziprasidone-specific stratum, these newer agents were not associated with an increased risk of diabetes and dose-dependent relationships were not apparent. Although, these estimates should be interpreted with caution as they are imprecise due to small numbers.
BMC Psychiatry 12/2011; 11:197. · 2.55 Impact Factor
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Jeffrey F Scherrer,
Lauren D Garfield,
Patrick J Lustman,
Paul J Hauptman,
Timothy Chrusciel,
Angelique Zeringue,
Robert M Carney,
Kenneth E Freedland,
Kathleen K Bucholz,
Richard Owen, John W Newcomer,
William R True
The American journal of medicine 07/2011; 124(7):e17. · 4.47 Impact Factor
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ABSTRACT: Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function.
We examined 60 adults aged 60 years and older, who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder. All subjects had pre-treatment and post-treatment assessments that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation.
Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks (measures of working memory and set shifting). Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes: memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo.
Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory. This finding suggests a novel treatment strategy in late-life anxiety disorders: targeting hypothalamic-pituitary- adrenal axis dysfunction to improve memory.
International Journal of Geriatric Psychiatry 06/2011; 27(5):454-62. · 2.42 Impact Factor
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Marc De Hert,
Dan Cohen,
Julio Bobes,
Marcelo Cetkovich-Bakmas,
Stefan Leucht,
David M Ndetei, John W Newcomer,
Richard Uwakwe,
Itsuo Asai,
Hans-Jurgen Möller,
Shiv Gautam,
Johan Detraux,
Christoph U Correll
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ABSTRACT: Physical disorders are, compared to the general population, more prevalent in people with severe mental illness (SMI). Although this excess morbidity and mortality is largely due to modifiable lifestyle risk factors, the screening and assessment of physical health aspects remains poor, even in developed countries. Moreover, specific patient, provider, treatment and system factors act as barriers to the recognition and to the management of physical diseases in people with SMI. Psychiatrists can play a pivotal role in the improvement of the physical health of these patients by expanding their task from clinical psychiatric care to the monitoring and treatment of crucial physical parameters. At a system level, actions are not easy to realize, especially for developing countries. However, at an individual level, even simple and very basic monitoring and treatment actions, undertaken by the treating clinician, can already improve the problem of suboptimal medical care in this population. Adhering to monitoring and treatment guidelines will result in a substantial enhancement of physical health outcomes. Furthermore, psychiatrists can help educate and motivate people with SMI to address their suboptimal lifestyle, including smoking, unhealthy diet and lack of exercise. The adoption of the recommendations presented in this paper across health care systems throughout the world will contribute to a significant improvement in the medical and related psychiatric health outcomes of patients with SMI.
World psychiatry: official journal of the World Psychiatric Association (WPA) 06/2011; 10(2):138-51. · 6.23 Impact Factor
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Jeffrey F Scherrer,
Lauren D Garfield,
Patrick J Lustman,
Paul J Hauptman,
Timothy Chrusciel,
Angelique Zeringue,
Robert M Carney,
Kenneth E Freedland,
Kathleen K Bucholz,
Richard Owen, John W Newcomer,
William R True
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ABSTRACT: The long-term risk of myocardial infarction (MI) associated with use of antidepressants is uncertain, especially for nontricyclic antidepressants. The present study uses a national Veterans Affairs cohort to test whether antidepressants increase or decrease risk of MI and all-cause mortality.
US Department of Veterans Affairs patient records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 25-80 years, who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating an episode of depression (n=93,653). Incident MI and all-cause mortality were modeled in patients who received 12 weeks or more of antidepressant pharmacotherapy as compared with 0-11 weeks during follow-up. Age-adjusted Cox proportional hazard models were computed before and after adjusting for baseline sociodemographics and time-dependent covariates.
Receipt of 12 or more weeks of continuous antidepressant therapy was associated with significantly reduced rates of incident MI across classes of antidepressants: selective serotonin reuptake inhibitor (SSRIs) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.44-0.52), serotonin-norepinephrine reuptake inhibitors (SNRIs) (HR 0.35; 95% CI, 0.32-0.40), tricyclic antidepressants (TCAs) (HR 0.39; 95% CI, 0.34-0.44), and "Other" (HR 0.41; 95% CI, 0.37-0.45). Risk of all-cause mortality also was decreased with receipt of 12 weeks of pharmacotherapy with all classes of antidepressants (SSRI, SNRI, TCA, Other), with HRs ranging from 0.50 to 0.66.
Across classes of antidepressants, 12 weeks of pharmacotherapy appears to be safe in terms of MI risk. Although the mechanism for this association remains uncertain, it is possible that compliance with pharmacotherapy for depression reflects compliance with cardiovascular medications. It also is possible that a direct drug effect or improved depressed mood may attenuate the risk of MI in depressed patients.
The American journal of medicine 04/2011; 124(4):318-24. · 4.47 Impact Factor
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Marc DE Hert,
Christoph U Correll,
Julio Bobes,
Marcelo Cetkovich-Bakmas,
Dan Cohen,
Itsuo Asai,
Johan Detraux,
Shiv Gautam,
Hans-Jurgen Möller,
David M Ndetei, John W Newcomer,
Richard Uwakwe,
Stefan Leucht
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ABSTRACT: The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. This excess mortality is mainly due to physical illness. We report prevalence rates of different physical illnesses as well as important individual lifestyle choices, side effects of psychotropic treatment and disparities in health care access, utilization and provision that contribute to these poor physical health outcomes. We searched MEDLINE (1966 - August 2010) combining the MeSH terms of schizophrenia, bipolar disorder and major depressive disorder with the different MeSH terms of general physical disease categories to select pertinent reviews and additional relevant studies through cross-referencing to identify prevalence figures and factors contributing to the excess morbidity and mortality rates. Nutritional and metabolic diseases, cardiovascular diseases, viral diseases, respiratory tract diseases, musculoskeletal diseases, sexual dysfunction, pregnancy complications, stomatognathic diseases, and possibly obesity-related cancers are, compared to the general population, more prevalent among people with SMI. It seems that lifestyle as well as treatment specific factors account for much of the increased risk for most of these physical diseases. Moreover, there is sufficient evidence that people with SMI are less likely to receive standard levels of care for most of these diseases. Lifestyle factors, relatively easy to measure, are barely considered for screening; baseline testing of numerous important physical parameters is insufficiently performed. Besides modifiable lifestyle factors and side effects of psychotropic medications, access to and quality of health care remains to be improved for individuals with SMI.
World psychiatry: official journal of the World Psychiatric Association (WPA) 02/2011; 10(1):52-77. · 6.23 Impact Factor
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ABSTRACT: The American Diabetes Association and American Psychiatric Association recommend metabolic monitoring for all patients using second-generation antipsychotic (SGA) drugs. We estimated glucose and lipid testing rates among SGA-users from three state Medicaid programs and investigated small area variation and patient and geographic determinants of testing.
A retrospective new-user cohort study using Medicaid claims data from California, Missouri, and Oregon was conducted among 30,563 patients in 207 counties starting SGA medication September 2004-December 2005. Adjusted odds ratios for state, county, and patient factors associated with testing were calculated from multivariable hierarchical logistic regression models.
Mean 6-month testing rates were 51.6% (glucose) and 26.2% (lipids). Screening rates were positively associated with the number of Type 2 diabetes risk factors (RF) present: glucose -39% (0 RF) to 82% (5 RF); lipids -13% (0 RF) to 66% (5 RF). A four-fold difference in glucose testing rates (21-85%) and a greater than six-fold difference in lipid testing rates (0-62%) were observed between counties. In the adjusted regression models, age, cardiometabolic co-morbidity (diabetes, dyslipidemia), serious mental illness, persistent use of SGAs, and frequency of non-psychiatric medical office visits were significant determinants of glucose and lipid testing. Lipid testing was more likely for children and adults in California, as was glucose testing for children.
Glucose and lipid testing among SGA-users varied significantly between states, counties, and by patient characteristics. More effort is needed to understand provider and system reasons for testing disparities in order to inform risk management quality improvement interventions.
Pharmacoepidemiology and Drug Safety 01/2011; 20(1):66-75. · 2.53 Impact Factor
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ABSTRACT: There is public health interest in the identification and treatment of modifiable cardiometabolic risk factors among patients treated with antipsychotic medications. However, best-practice screening recommendations endorsed by multiple medical organizations have not translated into real-world clinical practice. Quality improvement strategies may help to address the gap between policy and implementation. This column describes the successful implementation of a best-practice glucose screening program in a large network of community mental health centers that was based on Six Sigma and diffusion of innovation theory.
Psychiatric services (Washington, D.C.) 01/2011; 62(1):12-4. · 2.81 Impact Factor
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ABSTRACT: Schizophrenia is a persistent, lifelong illness such that enduring functional improvements may only occur over the course of years [corrected].This post hoc analysis in stable outpatients with schizophrenia investigated the negative symptom efficacy and treatment outcomes of ziprasidone (80-160 mg/d given twice a day, mean modal dose of 112 mg/d; and 80-120 mg/d given every day, mean modal dose of 96 mg/d) versus haloperidol (5-20 mg/d, mean modal dose of 12 mg/d) in a randomized, 40-week, double-blind study, followed by a double-blind continuation trial that extended up to 156 additional weeks. Symptomatic and functional recovery criteria were met when subjects attained both negative symptom remission and adequate psychosocial functioning based on the 4 Quality-of-Life subscales (instrumental role, interpersonal relations, participation in community, and intrapsychic foundations). Negative symptom remission (P = 0.005), as well as sustained adequate functioning (6 months) in instrumental role (P = 0.04) and participation in community (P = 0.02), was associated with significantly shorter time to remission in the ziprasidone 80 to 160 mg group than in the haloperidol group, as was the combination of symptomatic and functional recovery during the 196-week double-blind study period. A similar pattern was observed for the ziprasidone 80 to 120 mg group, which showed significant differences versus haloperidol in negative symptom remission and instrumental role functioning (but not other Quality-of-Life subscale measures). The clinically relevant outcome differences detected in this post hoc exploratory analysis support the potential for both enhanced remission in negative symptoms and psychosocial recovery during long-term treatment with an atypical agent and add to our understanding regarding the degree to which negative symptom remission can be attained in the maintenance phase.
Journal of clinical psychopharmacology 08/2010; 30(4):425-30. · 5.09 Impact Factor
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ABSTRACT: To estimate metabolic screening rates, predictors of screening, and incidence of metabolic disturbances in children initiating second-generation antipsychotic (SGA) drug treatment.
A retrospective, new-user cohort study (between July 1, 2004, and June 30, 2006) using Medicaid claims data.
California, Missouri, and Oregon.
A total of 5370 children (aged 6-17 years) without diabetes mellitus taking SGA drugs and 15,000 children without diabetes taking albuterol (control individuals) [corrected] but no SGA drugs.
Findings 1 year after recommendations from the American Diabetes Association and American Psychiatric Association called for metabolic screening of patients receiving SGA drugs.
Serum glucose and lipid testing, 6-month incidence of diabetes, and dyslipidemia disturbances.
Glucose screening was performed in 1699 (31.6% [95% confidence interval (CI), 30.4%-32.9%]) SGA-treated children vs 1891 (12.6% [12.1%-13.2%]) control individuals. Lipid testing was performed in 720 (13.4% [95% CI, 12.5%-14.4%]) SGA-treated children vs 458 (3.1% [2.8%-3.3%]) controls. In multivariate logistic regression analysis, children with serious and/or multiple psychiatric diagnoses and those who used health care services more intensively were more likely to receive metabolic screening. The case incidence of glucose and lipid disorders was higher in SGA-treated vs albuterol-treated children (8.9 per 1000 children [95% CI, 6.6%-11.8%] vs 4.9 per 1000 children [3.9%-6.2%]; and 9.7 per 1000 children [95% CI, 7.2%-12.7%] vs 4.6 per 1000 children [95% CI, 3.6%-5.8%], respectively).
Most children starting treatment with SGA medications in this public sector sample did not receive recommended glucose and lipid screening.
Archives of pediatrics & adolescent medicine 04/2010; 164(4):344-51. · 3.73 Impact Factor
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ABSTRACT: In 2003, the Food and Drug Administration (FDA) required a warning on diabetes risk for second-generation antipsychotic (SGA) drugs. The American Diabetes Association (ADA) and American Psychiatric Association (APA) recommended glucose and lipid testing for all patients starting to receive SGA drugs.
To characterize associations between the combined warnings and recommendations and baseline metabolic testing and SGA drug selection.
Interrupted time-series analysis.
California, Missouri, and Oregon. Patients A total of 109 451 individuals receiving Medicaid who began taking SGA medication and a control cohort of 203 527 patients who began taking albuterol but did not receive antipsychotic medication.
Prewarning and postwarning trends in metabolic testing were compared using laboratory claims for the cohort collected January 1, 2002, through December 31, 2005. Changes in SGA prescribing practices were similarly evaluated.
Monthly rates of baseline serum glucose and lipid testing for SGA-treated and propensity-matched albuterol-treated patients and monthly share of new prescriptions for each SGA drug.
Initial testing rates for SGA-treated patients were low (glucose, 27%; lipids, 10%). The warning was not associated with an increase in glucose testing among SGA-treated patients and was associated with only a marginal increase in lipid testing rates (1.7%; P = .02). Testing rates and trends in SGA-treated patients were not different from background rates observed in the albuterol control group. New prescriptions of olanzapine (higher metabolic risk) declined during the warning period (annual share decline, 19.9%; P < .001). New prescriptions of aripiprazole (lower metabolic risk) increased during the warning period (share increase, 12.1%; P < .001) but may be attributable to the elimination of prior authorization in California during the same time frame. Quetiapine, risperidone, and ziprasidone use were not associated with the warning.
In a Medicaid-receiving population, baseline glucose and lipid testing for SGA-treated patients was infrequent and showed little change following the diabetes warning and monitoring recommendations. A change in SGA drug selection consistent with intentions to reduce metabolic risk was observed.
Archives of general psychiatry 01/2010; 67(1):17-24. · 12.26 Impact Factor
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ABSTRACT: Routine metabolic screening and consideration of patient metabolic status in the choice of a second-generation antipsychotic (SGA) medication are recommended. This study evaluated the association between abnormal blood glucose and lipid values and SGA prescribing patterns.
A retrospective cohort study using administrative data from 2 managed care plans in the United States evaluated 7904 adults initiating SGA therapy between 2001 and 2004. Baseline serum glucose, total cholesterol, and triglyceride values were available for 989 patients (12.5%), and follow-up assessments were done in 699 patients (8.8%). Abnormal values were defined as the following: total cholesterol, 200 mg/dL or higher; triglycerides, 200 mg/dL or higher; and glucose, 126 mg/dL or higher. The likelihood of abnormal laboratory values being associated with selection of a lower metabolic risk SGA drug (aripiprazole or ziprasidone) and with switching decisions was assessed using multivariate logistic regression models.
Thirteen percent of the patients had glucose and lipid tests within 6 months of starting SGA therapy. The likelihood of starting a patient on an SGA drug with lower metabolic risk (ziprasidone: odds ratio, 3.26; 95% confidence interval, 1.25-8.47; aripiprazole: odds ratio, 2.13; 95% confidence interval, 0.77-5.88) was higher if the patient had elevated glucose values but was not associated with elevated cholesterol or triglyceride values or if the patient had preexisting diabetes or dyslipidemia. Abnormal glucose and lipid values were not associated with switching SGA medications in the first 6 months of therapy. Among patients who did switch SGA medications, elevated glucose and lipid values were not associated with a greater likelihood of switching to aripiprazole or ziprasidone.
Low rates of recommended monitoring were observed. Abnormal metabolic parameters among those who were tested were not consistently associated with the selection of an SGA drug with lower metabolic risk.
Journal of clinical psychopharmacology 03/2009; 29(1):26-32. · 5.09 Impact Factor
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ABSTRACT: The authors sought to quantify plasma lipid and glucose testing rates in patients receiving second-generation antipsychotics before and after guidelines recommending testing were issued in February 2004 by the American Diabetes Association (ADA).
In this retrospective cohort analysis using data from a large managed care database (PharMetrics, 2000-2006), patients under age 65 on second-generation antipsychotics were identified and followed from 40 days before to 130 days after the antipsychotic prescription was written. Baseline and 12-week (40 days) lipid and glucose testing rates were determined for pre- and postguideline cohorts. Logistic regression analyses determined predictors of baseline and 12-week lipid and glucose testing while controlling for covariates.
A total of 5,787 preguideline patients and 17,832 postguideline patients were identified. Baseline lipid testing rates were 8.4% for the preguideline cohort and 10.5% for the postguideline cohort, and the 12-week testing rates were 6.8% and 9.0%, respectively. Baseline glucose testing rates were 17.3% for the preguideline cohort and 21.8% for the postguideline cohort, and the 12-week testing rates were 14.1% and 17.9%, respectively. All four comparisons were statistically significant. Baseline and 12-week testing rates for lipids and glucose in children were the lowest of all age groups.
Despite statistically significant improvements after the ADA guidelines were issued, monitoring for plasma lipids and glucose in this population remains low. Clinicians and administrators responsible for the health of at-risk populations should implement new approaches for effective monitoring of major modifiable risk factors for medical morbidity and mortality in patients taking second-generation antipsychotics.
American Journal of Psychiatry 02/2009; 166(3):345-53. · 12.54 Impact Factor
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ABSTRACT: Several second-generation antipsychotic (SGA) drugs have been associated with weight gain, hyperglycemia, and dyslipidemia. We evaluated whether glucose and lipid testing increased after the American Diabetes Association (ADA) consensus statement recommending metabolic monitoring for SGA-treated patients.
Laboratory claims for serum glucose and lipid testing were identified for an incident cohort of 18,876 adults initiating SGA drugs in a U.S. commercial health plan (2001-2006) and a control group of 56,522 adults with diabetes not receiving antipsychotics. Interrupted time-series models were used to estimate the effect of ADA recommendations on baseline and annual testing trends after adjusting for differences in age, sex, mental health diagnoses, and cardiovascular risk using propensity score matching.
Mean baseline testing rates for SGA-treated patients during the study period were 23% (glucose) and 8% (lipids). Among persistent users of SGA medication, annual testing rates were 38% (glucose) and 23% (lipid). Before the ADA statement, screening rates for SGA-treated patients were increasing (glucose: baseline 3.6% per year, annual 7.2% per year; lipid: baseline 1.2% per year, annual 4.8% per year; P < 0.001 for each trend). Increases were similar to background testing trends in control subjects. The ADA statement was not associated with an increase in screening rates.
In a commercially insured population, glucose and lipid testing for SGA-treated adults was infrequent. A gradual increase in screening rates occurred over the 6-year period, but the changes were not temporally associated with the ADA statement. More effort is needed to improve diabetes and dyslipidemia screening in these at-risk patients.
Diabetes care 02/2009; 32(6):1037-42. · 8.09 Impact Factor
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John W Newcomer
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ABSTRACT: Patients with severe mental illnesses have a higher risk of premature mortality than the general US population. Illnesses such as schizophrenia and bipolar disorder are frequently complicated by physical comorbidities such as diabetes and cardiovascular disease, including both coronary heart disease and cerebrovascular disease, which are associated with increased mortality and morbidity. Coronary heart disease is the leading cause of death among individuals with severe mental illnesses. Modifiable risk factors such as dyslipidemia, hyperglycemia, hypertension, smoking, and obesity are common in this population and contribute to risk for both diabetes and coronary heart disease. While many psychotropic medications used in the treatment of schizophrenia or bipolar disorder have similar efficacy, some medications are associated with more metabolic side effects than others, and clinicians should consider these risks when choosing among these medications. Patients with severe mental illnesses tend to have reduced access to health care and treatment for medical comorbidities compared with the general population. Therefore, clinicians involved in the care of this patient population should screen and monitor carefully for cardiometabolic side effects and risk factors.
The Journal of Clinical Psychiatry 01/2009; 70 Suppl 3:30-6. · 5.80 Impact Factor
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John W Newcomer,
Jonathan M Meyer,
Ross A Baker,
James M Eudicone,
Andrei Pikalov,
Estelle Vester-Blokland,
Robert D McQuade,
David T Crandall,
William H Carson,
Ronald N Marcus,
Gilbert L'italien
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ABSTRACT: Non-high-density lipoprotein cholesterol (non-HDL-C) and the triglyceride to high-density lipoprotein cholesterol ratio (TG:HDL-C) are predictors of cardiovascular risk. This post-hoc analysis assessed changes in these parameters during treatment with the atypical antipsychotics olanzapine or aripiprazole using pooled data from three randomized, long-term clinical studies in patients with schizophrenia.
Data were pooled from one open-label and two double-blind (26- or 52-week) studies in patients randomized to olanzapine (5-20 mg/day) or aripiprazole (15-30 mg/day). Change from baseline in non-HDL-C levels between groups was analyzed in the Observed Case (OC) dataset at each time point and Last Observation Carried Forward (LOCF) dataset at endpoint using analysis of covariance, with treatment as main effect and baseline non-HDL-C as covariate. Differences between groups in median changes from baseline in TG:HDL-C were assessed with Kruskal-Wallis tests.
This analysis included 546 patients (olanzapine, n=274; aripiprazole, n=272). Mean changes from baseline in non-HDL-C levels were significantly different (p<0.0001) with olanzapine versus aripiprazole at Weeks 26 (+13.0 versus -7.5 mg/dL) and 52 (+12.2 versus -8.1 mg/dL). Baseline TG:HDL-C was high in the olanzapine (3.73) and aripiprazole (3.79) groups. Differences in median changes from baseline in TG:HDL-C were significant with olanzapine versus aripiprazole at Weeks 26 (+0.22 versus -0.54; p<0.0001) and 52 (+0.24 versus -0.62; p=0.004).
Long-term aripiprazole treatment is associated with improvements in lipid profiles of schizophrenia patients versus no improvement or worsening during olanzapine treatment. Consideration of cardiovascular risk is needed when prescribing antipsychotics, as is close monitoring for metabolic changes during treatment.
Schizophrenia Research 12/2008; 106(2-3):300-7. · 4.75 Impact Factor
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ABSTRACT: Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality, leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids, including use of antipsychotic agents with low metabolic risk. This multicenter, randomized, double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment.
In total, 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were randomly assigned to receive aripiprazole (N = 88) or olanzapine (N = 85) for 16 weeks in a study conducted from March 30, 2004, to August 8, 2006. Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels, respectively.
At week 16, weight decreased significantly with aripiprazole versus olanzapine (-1.8 vs. +1.41 kg; p < .001). Significant differences in percentage change in triglyceride levels were observed with aripiprazole (decreases) versus olanzapine (increases) at all time-points. In addition, significantly more subjects receiving aripiprazole had clinically relevant (> or = 7%) weight loss versus olanzapine (11.1% vs. 2.6%; p = .038), and a lower percentage of subjects receiving aripiprazole had clinically relevant weight gain (2.5% vs. 9.1%; p = .082). Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine, with no significant effects on glycemic laboratory measures. Mean Clinical Global Impressions-Improvement (CGI-I) scores for both groups were in the range of "no change" to "minimal improvement." CGI-I endpoint scores were statistically significantly better with olanzapine (mean +/- SE = 3.09 +/- 0.16) versus aripiprazole (mean +/- SE = 3.74 +/- 0.15; p < .001), and more subjects discontinued aripiprazole (N = 32/88; 36%) than olanzapine (N = 22/85; 26%).
Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects, relative to uninterrupted continuation of olanzapine treatment. The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population.
The Journal of Clinical Psychiatry 07/2008; 69(7):1046-56. · 5.80 Impact Factor
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John W Newcomer
CNS spectrums 06/2008; 13(6 Suppl 10):1-14. · 2.20 Impact Factor
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CNS spectrums 06/2008; 13(6 Suppl 10):13-4. · 2.20 Impact Factor
