National trends in second-generation antipsychotic augmentation for nonpsychotic depression.
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ABSTRACT: 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.
SUBMITTER: Gerhard T
PROVIDER: S-EPMC8215591 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceRandomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression.ObjectiveThis study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression.DesignPopulation-based new-user/active comparator cohort study.SettingNational healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index.ParticipantsNon-elderly adults (25-64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded.ExposureAugmentation treatment for depression with a newer antipsychotic or with a second antidepressant.Main outcomeAll-cause mortality during study follow-up ascertained from the National Death Index.ResultsThe analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses.ConclusionAugmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation.
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| S-EPMC4756722 | biostudies-other
Project description:PurposeTo study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM).MethodsA population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models.ResultsUse of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results.ConclusionsOlanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.
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Project description:In this meta-analysis, we aimed to estimate and compare the efficacy of add-on treatment of antidepressants with esketamine nasal spray and second-generation antipsychotics in patients with nonpsychotic major depressive disorder and inadequate response to antidepressants. Searching for acute-phase, double-blind, placebo-controlled, randomized trials, we found 22 second-generation antipsychotic (n = 8363) and 3 intranasal esketamine (n = 641) studies. Mean change in the Montgomery Åsberg Depression Rating Scale total score served as outcome. We determined a higher mean difference (vs placebo) for the pooled esketamine nasal spray trials (mean difference = 4.09, 95% confidence interval: 2.01 to 6.17) than for the pooled second-generation antipsychotic augmentation trials (mean difference = 2.05, 95% confidence interval: 1.51 to 2.59). Thus, the effect size for intranasal esketamine was nearly twice as high as those for the second-generation antipsychotics. This indicates high efficacy of add-on esketamine nasal spray in treatment-resistant major depressive disorder compared with other well-established, evidence-based pharmacological options such as augmentation with second-generation antipsychotics.
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Project description:BACKGROUND:Observational studies of older adults showed higher mortality for first-generation antipsychotics than their second- generation counterparts, which led to US Food and Drug Administration warnings, but the actual mechanisms involved remain unclear. METHODS:A cohort of 9,060 initiators of first-generation antipsychotics and 17,137 of second-generation antipsychotics enrolled in New Jersey and Pennsylvania Medicare were followed for 180 days. Medical events were assessed using diagnostic and procedure codes on inpatient billing claims. For the individual and joint set of medical events (mediators), we estimated the total, direct, and indirect effects of antipsychotic type (first versus second generation) on mortality on the risk ratio scale and the proportion mediated on the risk difference scale, obtaining 95% confidence intervals through bootstrapping. We performed bias analyses for false-negative mediator misclassification in claims data, with sensitivity ranging from 0.25 to 0.75. RESULTS:There were 3,199 deaths (outcomes), 862 cardiovascular events, 675 infectious events, and 491 hip fractures (potential mediators). Mortality was higher for first- than second-generation antipsychotic initiators (adjusted risk ratio: 1.14; 95% confidence interval: 1.06, 1.22). In naïve analyses, that ignored potential misclassification, less than 4% of this difference was explained by any particular medical event. In bias analyses, the proportion mediated ranged from 6% to 16% for stroke, 3% to 9% for ventricular arrhythmia, 3% to 11% for myocardial infarction, 0% venous thromboembolism, 3% to 9% for pneumonia, 0% to 1% for other bacterial infection, and 1% to 3% for hip fracture. CONCLUSIONS:Acute cardiovascular events and pneumonia may explain part of the mortality difference between first- and second-generation antipsychotic initiators in this analysis.
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Project description:BackgroundThe concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics.MethodsWe searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents.ResultsWe included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4 mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available.ConclusionsThe classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of "minimum effective dose methods" and "dose-response curve methods." In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods.
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Project description:Reducing overuse of second-generation antipsychotics among Medicaid-enrolled children is a national priority, yet little is known about how service organization affects use. This study compared differences in second-generation antipsychotic utilization among Medicaid-enrolled children across fee-for-service, integrated managed care, and managed behavioral health carve-out organizational structures.Organizational structures of Medicaid programs in 82 diverse counties in 34 states were categorized and linked to child-level cross-sectional claims data from the Medicaid Analytic Extract covering fiscal years 2004, 2006, and 2008. To approximate the population at risk of antipsychotic treatment, the sample was restricted to stimulant-using children ages three to 18 (N=419,226). The sample was stratified by Medicaid eligibility group, and logistic regression models were estimated for probability of second-generation antipsychotic use. Models included indicators of county-level organizational structure as main predictors, with sequential adjustment for personal and county-level covariates.With adjustment for person-level covariates, second-generation antipsychotic use was 31% higher among youths in foster care in fee-for-service counties than for youths in counties with carve-outs (odds ratio [OR]=1.69, 95% confidence interval [CI]=1.26-2.27). Foster care youths in integrated counties had the second highest adjusted odds (OR=1.31, CI=1.08-1.58). Similar patterns of use also were found for youths eligible for Supplemental Security Income but not for those eligible for Temporary Assistance for Needy Families. Differences persisted after adjustment for county-level characteristics.Carve-outs, versus other arrangements, were associated with lower second-generation antipsychotic use. Future research should explore carve-out features (for example, tighter management of inpatient or restricted access, as well as care coordination) contributing to lower second-generation antipsychotic use.
| S-EPMC4757898 | biostudies-literature
Project description:BackgroundNon-adherence is a significant problem in bipolar disorder. Second-generation antipsychotics (SGA) long-acting injections (LAIs) may improve adherence in bipolar disorder and may prevent relapses. However, the evidence is limited and conflicting.ObjectiveThe objective of this study was to evaluate efficacy and safety of SGA LAIs in bipolar disorder.MethodSystematic review and meta-analysis of randomised controlled trials (RCTs) (≥6 months duration) investigating safety and efficacy of SGA LAIs for bipolar disorder. We searched Pubmed, Embase, CINAHL, Cochrane, PsycINFO, LiLACS, www.clinicaltrials.gov up to October 2016. We also contacted the manufacturers of SGA LAIs. Primary efficacy and safety outcomes were relapse rate and all-cause discontinuation respectively.ResultsTotal of seven RCTs (n = 1192) were included. SGA LAIs show superiority over placebo for study-defined relapse rate (RR = 0.58, 95% CI = 0.49-0.68, P < 0.00001) and all-cause discontinuation (RR = 0.72, 95% CI = 0.64-0.82, P < 0.00001). However, no significant difference was found between SGA LAIs and oral active control for relapse rate (RR = 0.92, P = 0.79) and all-cause discontinuation (RR = 1.2, P = 0.31). In terms of secondary outcomes, SGA LAIs performed better than placebo in relapse to mania/hypomania, young mania rating scales (YMRS), clinical global impression-severity (CGI-S), montgomery-asberg depression rating scale (MADRS). There was no significant difference between SGA LAIs and oral active control regarding relapse to mania/hypomania, YMRS, CGI-S, extra-pyramidal side effects (EPSEs), weight gain. However, the active control performed better than SGA LAIs in relapse to depression, MADRS, and prolactin-related AEs.ConclusionsCurrent evidence is very limited to support the use of SGA LAIs (compared to oral medication) in bipolar disorder. Further high-quality studies, particularly comparing SGA LAIs with active control, are warranted.
| S-EPMC6587954 | biostudies-literature
Project description:BackgroundAntipsychotics are frequently prescribed to children and adolescents for nonpsychotic indications. Guidelines recommend regularly assessing treatment response and adverse effects and the ongoing need for their use. We aimed to assess adherence to recommendations of available guidelines regarding monitoring antipsychotic use and to test the influence of children's age, sex, intelligence quotient, and diagnosis on adherence.MethodsWe reviewed 426 medical records from 26 centers within 3 large Dutch child and adolescent psychiatry organizations, excluding children with schizophrenia, psychosis, mania, or an intelligence quotient below 70. We investigated whether there was regular assessment of treatment response, adverse events (physical and laboratory), and at least annual discussion of the need of continued use.ResultsOn average, treatment response was assessed in 69.3% of the recommended treatment periods, height in 25.6%, weight in 30.6%, blood pressure in 20.6%, evaluation of adverse events in 19.4%, and cardiometabolic measures in 13.7%; discontinuation and/or continued need was discussed at least annually in 36.2%. Extrapyramidal and prolactin-related adverse effects, waist circumference, glucose, and lipids were rarely investigated. Higher age was associated with lower rates of assessment of treatment response. Most antipsychotics were prescribed long-term. In those children with sufficient documentation of the course of treatment, 57.7% was still using an antipsychotic 3 years after initiation.ConclusionsOur findings indicate insufficient adherence to guideline recommendations for monitoring antipsychotic use in children and adolescents, as well as long duration of use in the majority of children. Especially, older children are at higher risk of receiving suboptimal care.
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