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Peter Manu - One of the best experts on this subject based on the ideXlab platform.
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cardiometabolic risk of Second Generation Antipsychotic medications during first time use in children and adolescents
JAMA, 2009Co-Authors: Christoph U Correll, Peter Manu, Vladimir Olshanskiy, Barbara Napolitano, John M Kane, Anil K MalhotraAbstract:Context Cardiometabolic effects of Second-Generation Antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to Antipsychotic medication. Objective To study the association of Second-Generation Antipsychotic medications with body composition and metabolic parameters in patients without prior Antipsychotic medication exposure. Design, Setting, and Patients Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of Antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients who completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group. Intervention Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks. Main Outcome Measures Weight gain and changes in lipid and metabolic parameters. Results After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, −1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P Conclusions First-time Second-Generation Antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 Antipsychotic medications.
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metabolic syndrome and the risk of coronary heart disease in 367 patients treated with Second Generation Antipsychotic drugs
The Journal of Clinical Psychiatry, 2006Co-Authors: Christoph U Correll, John M Kane, Anne M Frederickson, Peter ManuAbstract:OBJECTIVE To examine the relationship between presence of metabolic syndrome and the risk of coronary heart disease (CHD) events (angina pectoris, myocardial infarction, and sudden cardiac death) in patients treated with Second-Generation Antipsychotic medications. METHOD 367 adults treated with Second-Generation Antipsychotics randomly selected from consecutive psychiatric admissions to a single hospital between August 1, 2004, and March 1, 2005, underwent assessments evaluating the presence of metabolic syndrome. The 10-year risk of CHD events was calculated according to the Framingham scoring system for age, smoking, total cholesterol, high-density lipoprotein (HDL)-cholesterol, blood pressure, and history of diabetes and was compared in patients with and without the metabolic syndrome. RESULTS Metabolic syndrome, present in 137 patients (37.3%), was associated with a significantly greater age- and race-adjusted 10-year risk of CHD events, i.e., 11.5% vs. 5.3% for men (risk ratio = 2.18, 95% CI = 1.88 to 2.48, p < .0001) and 4.5% vs. 2.3% for women (risk ratio = 1.94, 95% CI = 1.65 to 2.23, p = .0005). The increased risk of CHD events in patients with metabolic syndrome remained significant after the exclusion of diabetic patients. In a logistic regression analysis of variables independent of the Framingham scoring system, triglyceride levels (p < .0001), waist circumference (p = .035), and white race (p = .047) were significantly associated with the 10-year risk of CHD events (R2 = 0.134; p < .0001). CONCLUSIONS These data confirm the high prevalence of metabolic syndrome in patients receiving Second-Generation anti-psychotics, indicate that metabolic syndrome doubles the 10-year risk of CHD events in this population, and emphasize the importance of the "hypertriglyceridemic waist" for the identification of psychiatric patients at high risk of CHD.
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Cost-effective screening for the metabolic syndrome in patients treated with Second-Generation Antipsychotic medications
The American journal of psychiatry, 2005Co-Authors: David Straker, Christoph U Correll, John M Kane, Elisse Kramer-ginsberg, Nasreen Abdulhamid, Fiju Koshy, Elayna Rubens, Robert Saint-vil, Peter ManuAbstract:OBJECTIVE: Despite concerns about the adverse effects of Second-Generation Antipsychotics on weight regulation and glucose and lipid metabolism, little is known about the relationship between these agents and the metabolic syndrome. Because the metabolic syndrome is more strongly associated with cardiovascular morbidity and mortality than its individual components, attention to the full syndrome is important. The authors’ goal was to explore the relationship between Second-Generation Antipsychotics and the metabolic syndrome. METHOD: They assessed the prevalence of metabolic syndrome in a nearly consecutive group of 89 acutely admitted psychiatric inpatients treated with at least one Second-Generation Antipsychotic for different psychiatric disorders. Patients’ waist circumference and blood pressure were measured as well as their fasting blood glucose and lipid levels. RESULTS: Twenty-six (29.2%) of the 89 patients fulfilled criteria for the metabolic syndrome. Presence of the syndrome was associated with...
Jamie J Coleman - One of the best experts on this subject based on the ideXlab platform.
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Second Generation Antipsychotic drug use in hospital inpatients with dementia the impact of a safety warning on rates of prescribing
Journal of Public Health, 2015Co-Authors: Graham Mcilroy, Sarah K Thomas, Jamie J ColemanAbstract:Background Behavioural and psychological symptoms of dementia are distressing for patients and are frequently treated with Second-Generation Antipsychotics. Concerns about the drugs’ safety resulted in a Medicines and Healthcare Products Regulatory Agency (MHRA) warning against their use in March 2009. Methods Second-Generation Antipsychotic drug use was determined amongst patients with dementia admitted to the University Hospitals Birmingham National Health Service Foundation Trust, between July 2005 and December 2011. An interrupted time series analysis was carried out to investigate changes in rates of prescribing following the safety warning. Risperidone was analysed separately, in accordance with its limited licence for use in older adults with dementia, granted in October 2008. Results Before the safety warning, Second-Generation Antipsychotic use was increasing in patients with dementia. After the MHRA warning, their use fell by 1.9% per month compared with that before. Use of risperidone continued to rise over the same period, often against the terms of its licence.
Christoph U Correll - One of the best experts on this subject based on the ideXlab platform.
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Current and Novel Approaches to Mitigate Cardiometabolic Adverse Effects of Second-Generation Antipsychotics.
The international journal of neuropsychopharmacology, 2020Co-Authors: Karolina Skonieczna-Żydecka, Igor Łoniewski, Ewa Stachowska, Wojciech Marlicz, Christoph U CorrellAbstract:Second-Generation Antipsychotic-related weight gain and metabolic disturbances are a major public health issue given the widespread prescribing of these medications. The lack of clearly known mechanisms of cardiometabolic adverse effects and the relevance of cardiometabolic health for survival make this an important area for research. While nonpharmacologic and some pharmacologic treatments have shown benefits vs control conditions or placebo, the effects are modest and long-term benefits are less clear. Therefore, new approaches to mitigate Second-Generation Antipsychotic-associated cardiometabolic burden are sorely needed.
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national trends in Second Generation Antipsychotic augmentation for nonpsychotic depression
The Journal of Clinical Psychiatry, 2014Co-Authors: Tobias Gerhard, Christoph U Correll, Stephen Crystal, Ayse Akincigil, Neil J Foglio, Mark OlfsonAbstract:OBJECTIVE This study estimates national trends and patterns in use of Second-Generation Antipsychotics (SGAs) for adjunctive treatment of nonpsychotic adult depression in office-based practice. METHOD Twelve consecutive years (1999-2010) of the National Ambulatory Medical Care Survey were analyzed to estimate trends and patterns of adjunctive SGA treatment for adult (≥ 18 years) nonpsychotic depression in office-based visits. Adjunctive SGA use was examined among all office visits in which depression was diagnosed (N = 7,767), excluding visits with diagnoses for alternative SGA indications (schizophrenia, bipolar disorder, pervasive development disorder, psychotic depression, dementia) and those without an active antidepressant prescription. RESULTS From 1999 to 2010, 8.6% of adult depression visits included an SGA. SGA use rates increased from 4.6% in 1999-2000 to 12.5% in 2009-2010, with an adjusted odds ratio (AOR) for time trend of 2.78 (95% CI, 1.84-4.20). The increase in SGA augmentation was broad-based, with no significant differences in time trends between demographic and clinical subgroups. For the most recent survey years (2005-2010), SGA use rates were higher in visits to psychiatrists than to other physicians (AOR = 5.08; 95% CI, 2.96-8.73), visits covered by public than private insurance (AOR = 3.20; 95% CI, 2.25-4.54), visits with diagnosed major depressive disorder than other depressive disorders (AOR = 1.49; 95% CI, 1.08-2.06), and visits with diabetes, hyperlipidemia, or cardiovascular disease (AOR = 2.13; 95% CI, 1.12-4.03) and lower in visits by patients > 65 years than 18-44 years (AOR = 0.51; 95% CI, 0.32-0.82) and visits that included psychotherapy (AOR = 0.68; 95% CI, 0.47-0.96). CONCLUSIONS Between 1999 and 2010, SGAs were increasingly accepted in the outpatient treatment of adult nonpsychotic depression.
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cardiometabolic risk of Second Generation Antipsychotic medications during first time use in children and adolescents
JAMA, 2009Co-Authors: Christoph U Correll, Peter Manu, Vladimir Olshanskiy, Barbara Napolitano, John M Kane, Anil K MalhotraAbstract:Context Cardiometabolic effects of Second-Generation Antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to Antipsychotic medication. Objective To study the association of Second-Generation Antipsychotic medications with body composition and metabolic parameters in patients without prior Antipsychotic medication exposure. Design, Setting, and Patients Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of Antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients who completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group. Intervention Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks. Main Outcome Measures Weight gain and changes in lipid and metabolic parameters. Results After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, −1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P Conclusions First-time Second-Generation Antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 Antipsychotic medications.
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metabolic syndrome and the risk of coronary heart disease in 367 patients treated with Second Generation Antipsychotic drugs
The Journal of Clinical Psychiatry, 2006Co-Authors: Christoph U Correll, John M Kane, Anne M Frederickson, Peter ManuAbstract:OBJECTIVE To examine the relationship between presence of metabolic syndrome and the risk of coronary heart disease (CHD) events (angina pectoris, myocardial infarction, and sudden cardiac death) in patients treated with Second-Generation Antipsychotic medications. METHOD 367 adults treated with Second-Generation Antipsychotics randomly selected from consecutive psychiatric admissions to a single hospital between August 1, 2004, and March 1, 2005, underwent assessments evaluating the presence of metabolic syndrome. The 10-year risk of CHD events was calculated according to the Framingham scoring system for age, smoking, total cholesterol, high-density lipoprotein (HDL)-cholesterol, blood pressure, and history of diabetes and was compared in patients with and without the metabolic syndrome. RESULTS Metabolic syndrome, present in 137 patients (37.3%), was associated with a significantly greater age- and race-adjusted 10-year risk of CHD events, i.e., 11.5% vs. 5.3% for men (risk ratio = 2.18, 95% CI = 1.88 to 2.48, p < .0001) and 4.5% vs. 2.3% for women (risk ratio = 1.94, 95% CI = 1.65 to 2.23, p = .0005). The increased risk of CHD events in patients with metabolic syndrome remained significant after the exclusion of diabetic patients. In a logistic regression analysis of variables independent of the Framingham scoring system, triglyceride levels (p < .0001), waist circumference (p = .035), and white race (p = .047) were significantly associated with the 10-year risk of CHD events (R2 = 0.134; p < .0001). CONCLUSIONS These data confirm the high prevalence of metabolic syndrome in patients receiving Second-Generation anti-psychotics, indicate that metabolic syndrome doubles the 10-year risk of CHD events in this population, and emphasize the importance of the "hypertriglyceridemic waist" for the identification of psychiatric patients at high risk of CHD.
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Cost-effective screening for the metabolic syndrome in patients treated with Second-Generation Antipsychotic medications
The American journal of psychiatry, 2005Co-Authors: David Straker, Christoph U Correll, John M Kane, Elisse Kramer-ginsberg, Nasreen Abdulhamid, Fiju Koshy, Elayna Rubens, Robert Saint-vil, Peter ManuAbstract:OBJECTIVE: Despite concerns about the adverse effects of Second-Generation Antipsychotics on weight regulation and glucose and lipid metabolism, little is known about the relationship between these agents and the metabolic syndrome. Because the metabolic syndrome is more strongly associated with cardiovascular morbidity and mortality than its individual components, attention to the full syndrome is important. The authors’ goal was to explore the relationship between Second-Generation Antipsychotics and the metabolic syndrome. METHOD: They assessed the prevalence of metabolic syndrome in a nearly consecutive group of 89 acutely admitted psychiatric inpatients treated with at least one Second-Generation Antipsychotic for different psychiatric disorders. Patients’ waist circumference and blood pressure were measured as well as their fasting blood glucose and lipid levels. RESULTS: Twenty-six (29.2%) of the 89 patients fulfilled criteria for the metabolic syndrome. Presence of the syndrome was associated with...
Elaine H. Morrato - One of the best experts on this subject based on the ideXlab platform.
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Lipid profile screening in Second-Generation Antipsychotic users: the gap between policy and practice
Clinical Lipidology, 2010Co-Authors: Elaine H. Morrato, Daniel M. HartungAbstract:“Given the significant cardiometabolic risks associated with the use of Second-Generation Antipsychotic drugs, it is particularly troubling that rates of dyslipidemia screening and monitoring are s...
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metabolic testing rates in 3 state medicaid programs after fda warnings and ada apa recommendations for Second Generation Antipsychotic drugs
Archives of General Psychiatry, 2010Co-Authors: Elaine H. Morrato, Daniel M. Hartung, Benjamin G Druss, Robert J Valuck, Richard P Allen, Elizabeth J Campagna, John W NewcomerAbstract:Context 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. Objective To characterize associations between the combined warnings and recommendations and baseline metabolic testing and SGA drug selection. Design Interrupted time-series analysis. Setting 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. Interventions 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. Main Outcome Measures 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. Results 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 Conclusions 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.
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metabolic risk status and Second Generation Antipsychotic drug selection a retrospective study of commercially insured patients
Journal of Clinical Psychopharmacology, 2009Co-Authors: Elaine H. Morrato, Brian Cuffel, John W Newcomer, Ilise Lombardo, Siddhesh Kamat, John BarronAbstract:Background: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.Materials and Me
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prevalence of baseline serum glucose and lipid testing in users of Second Generation Antipsychotic drugs a retrospective population based study of medicaid claims data
The Journal of Clinical Psychiatry, 2008Co-Authors: Elaine H. Morrato, John W Newcomer, Richard R Allen, Robert J ValuckAbstract:Objective: Increased risk of diabetes and dyslipidemia is associated with major mental illness and Antipsychotic drug use. This study aimed to determine the prevalence of serum glucose and lipid monitoring in public mental health clients initiating Second-Generation Antipsychotic (SGA) drugs. Method: This retrospective cohort study using Medicaid claims data from California, Oregon, Tennessee, and Utah evaluated 55,436 enrollees with a prescription claim for an SGA drug between January 1, 1998, and December 31, 2003. Serum glucose and lipid testing were identified using Current Procedural Terminology (CPT) procedure codes. Baseline was defined as 14 days before through 28 days after the date of the first SGA prescription. Multivariate logistic regression identified patient characteristics associated with testing. Generalized estimating equations evaluated changes associated with SGA drug initiation compared to background rates of testing. Results: On average, < 20% of individuals initiating SGA drug therapy received baseline glucose testing, and < 10% received baseline lipid testing. Baseline glucose and lipid testing increased modestly with SGA initiation (glucose: 7%-11% increase; lipids: 2%-3% increase; p <.001). Preexisting diabetes and dyslipidemia were associated with a 2- to 3-fold greater likelihood of baseline glucose and lipid testing. The likelihood of glucose testing increased 2-fold between 1998 and 2003 and was 46% more likely in patients with schizophrenia. Enrollees from Oregon, Tennessee, and Utah were 50% to 90% less likely to receive baseline glucose or lipid testing than enrollees from California. Conclusions: Glucose and lipid screening is underutilized in patients initiating SGA drug therapy. Psychiatrists can play an important role to ensure metabolic risk is adequately assessed.
Stefan Leucht - One of the best experts on this subject based on the ideXlab platform.
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fat mass and obesity related gene variants rs9939609 and rs7185735 are associated with Second Generation Antipsychotic induced weight gain
Pharmacopsychiatry, 2018Co-Authors: Charlotte Schroder, Stefan Leucht, Fabian Czerwensky, Werner SteimerAbstract:Introduction Weight gain is a limiting and frequent adverse effect of Second-Generation Antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy. Methods We focused on rs7185735 and rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity-associated (FTO) gene reported to be associated with obesity. Three-hundred fifty Caucasian inpatients were included in a naturalistic study. Results After 4 weeks of treatment, we did not observe any significant association of polymorphisms with weight change in the whole study population (p>0.05). In a subpopulation without additional weight-inducing comedication (n=178), G-allele carriers of rs7185735 gained 3.4 times more weight (1.69 kg±3.1 kg, p=0.019) than AA genotypes (0.49 kg±3.1 kg). A-allele carriers of rs9939609 gained 3.1 times more weight (1.65 kg±3.1 kg, p=0.029) than TT genotypes (0.54 kg±3.2 kg). Discussion Our findings confirm the role of the FTO gene as a high-potential risk factor for obesity and indicate a value for predicting a weight gain induced by Second-Generation Antipsychotics. Further, we detected an additive effect of FTO rs7185735 and MC4R rs17782313.
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mc4r rs489693 a clinical risk factor for Second Generation Antipsychotic related weight gain
The International Journal of Neuropsychopharmacology, 2013Co-Authors: Fabian Czerwensky, Stefan Leucht, Werner SteimerAbstract:Weight gain is a therapy limiting and very frequent adverse effect of many Second-Generation Antipsychotic (SGA) drugs. The human melanocortin four receptor (MC4R) is a very promising candidate gene possibly influencing SGA-related weight gain. The rs489693 polymorphism near the MC4R gene was associated with SGA-related weight gain in a genome-wide association study. We tried to replicate these results in our independent naturalistic study population. From 341 Caucasian inpatients receiving at least one SGA drug (olanzapine, clozapine, risperidone, paliperidone, quetiapine or amisulpride), carriers homozygous for the rs489693 A-allele (n = 35) showed a 2.2 times higher weight increase (+2.2 kg) than carriers of the CC-genotype (+1 kg) after 4 wk of treatment (analysis of covariance, p = 0.039). We revealed an even stronger effect in a subpopulation without weight gain inducing co-medication (factor 3.1, +2.8 kg, p = 0.044, (n = 16 of 169)) and in first episode patients (factor 2.7, +2.7 kg, p = 0.017, (n = 13 of 86)). Our results confirm the rs489693 A-allele as a possible risk factor for SGA-related weight gain.
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How effective are Second-Generation Antipsychotic drugs? A meta-analysis of placebo-controlled trials
Molecular Psychiatry, 2009Co-Authors: Stefan Leucht, Dieter Arbter, R R Engel, W Kissling, J M DavisAbstract:We conducted a systematic review and meta-analysis of randomized controlled trials that compared Second-Generation Antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA drugs were more effective than placebo, but the pooled effect size (ES) for overall symptoms (primary outcome) was moderate (−0.51). The absolute difference (RD) in responder rates was at 18% (41% responded to drug compared with 24% to placebo, number needed to treat=6). Similar ESs were found for the other efficacy parameters: negative symptoms (ES=−0.39), positive symptoms (ES=−0.48), depression (ES=−0.26), relapse (RD 20%) and discontinuation due to inefficacy (RD 17%). Curiously, the efficacy of haloperidol for negative and depressive symptoms was similar to that of the SGA drugs. In contrast to haloperidol, there was no difference in terms of EPS between any SGA drugs and placebo, and there was also no difference in terms of dropouts due to adverse events. Meta-regression showed a decline in treatment response over time, and a funnel plot suggested the possibility of publication bias. We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate, and that there is much room for more efficacious compounds. Whether methodological issues account in part for the relatively low efficacy ESs and the scarcity of adverse event differences compared with placebo needs to be established.
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Second Generation versus first Generation Antipsychotic drugs for schizophrenia a meta analysis
The Lancet, 2009Co-Authors: Stefan Leucht, Caroline Corves, Dieter Arbter, Rolf R. Engel, Chunbo Li, John M. DavisAbstract:Summary Background Because of the debate about whether Second-Generation Antipsychotic drugs are better than first-Generation Antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine Second-Generation Antipsychotic drugs with first-Generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured Second-Generation drugs. Four of these drugs were better than first-Generation Antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride −0·31 [95% CI −0·44 to −0·19, p Interpretation Second-Generation Antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost. Funding National Institute of Mental Health.
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Second Generation versus first Generation Antipsychotic drugs for schizophrenia a meta analysis commentary
The Lancet, 2009Co-Authors: Peter Tyrer, Timothy J. Kendall, Stefan Leucht, Caroline Corves, Dieter Arbter, Rolf R. Engel, John M. DavisAbstract:Background Because of the debate about whether Second-Generation Antipsychotic drugs are better than first-Generation Antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine Second-Generation Antipsychotic drugs with first-Generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21533 participants. We excluded open studies because they systematically favoured Second-Generation drugs. Four of these drugs were better than first-Generation Antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride -0.31 [95% CI -0.44 to -0.19, p<0.0001], clozapine -0.52 [-0.75 to -0.29, p<0.0001], olanzapine -0.28 [-0.38 to -0.18, p<0.0001], and risperidone -0.13 [-0.22 to -0.05, p=0.002]). The other Second-Generation drugs were not more efficacious than the first-Generation drugs, even for negative symptoms. Therefore efficacy on negative symptoms cannot be a core component of atypicality. Second-Generation Antipsychotic drugs induced fewer extrapyramidal side-effects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-effects than low-potency first-Generation Antipsychotic drugs. With the exception of aripiprazole and ziprasidone, Second-Generation Antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol but not than low-potency first-Generation drugs. The Second-Generation drugs also differed in their sedating properties. We did not note any consistent effects of moderator variables, such as industry sponsorship, comparator dose, or prophylactic antiparkinsonian medication. Interpretation Second-Generation Antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost.
