Second-generation Antipsychotic Initiation Research Articles

Trajectories and Predictors for the Development of Clinically Significant Weight Gain in Children and Adolescents Prescribed Second-Generation Antipsychotics.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Associated Weight Gain Among Children and Adolescents.

Antipsychotic-associated weight gain (AAWG) is a common adverse effect of second-generation antipsychotic (SGA) medications among children and adolescents. This study applied group-based trajectory modeling to identify latent trajectories of AAWG among children and adolescents and associated risk factors. This was a retrospective analysis of the IQVIA Ambulatory EMR-US database from 2016 to 2021. The cohort consisted of patients aged 6 to 19 years who were SGA naive and received at least 90 days of continuous SGA prescriptions. Group-based trajectory modeling was used to identify latent trajectories of AAWG development during a 24-month period since SGA initiation, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the identified AAWG trajectories. A total of 16,262 patients were included. Group-based trajectory modeling identified the following 4 distinctive AAWG trajectories: persistent severe weight gain (4.2%), persistent moderate weight gain (20.1%), minor weight change (69.6%), and gradual weight loss (6.1%). Compared with the minor weight change group, younger age (12-17 vs 5-11: odds ratio [OR], 0.634; 95% confidence interval [CI], 0.521-0.771), lower baseline body mass index z -score (OR, 0.216; 95% CI, 0.198-0.236), and receiving olanzapine as the initial SGA (olanzapine vs aripiprazole: OR, 1.686; 95% CI, 1.673-1.699) were more likely to follow severe weight gain trajectories. The area under the receiver operating characteristic curves for comparing severe weight gain versus minor weight change groups and moderate weight vs minor weight change groups in the multinomial regression model were 0.91 and 0.8, respectively. A quarter of pediatric SGA recipients experienced persistent weight gain during the SGA treatment. The risk of having persistent AAWG can be predicted using patient characteristics collected before SGA initiation and the initial SGA agent.

Medication Gaps and Antipsychotic Polypharmacy in Previously Hospitalized Schizophrenia Patients: An Electronic Cohort Study in Three Canadian Provinces

BackgroundReal world evidence about antipsychotics focuses on rehospitalization. Modeling the time course of pharmacotherapy would show patients' adherence to medications and physicians' adherence to medication guidelines. We aimed to calculate the cumulative time spent in second generation antipsychotics (SGAs), gaps, antipsychotic polypharmacy, and clozapine in discharged schizophrenia patients.MethodsHospitalization and pharmacy dispensing data from 2008–2018 in Manitoba, Saskatchewan, and British Columbia were linked and an electronic cohort (N = 2,997) was created (mean follow-up: 49 months, SD = 38). Cohort members were required to have a minimum of 6 weeks medicated with aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone.ResultsThe multistate model predicted that schizophrenia patients accumulated 44 months in SGA monotherapy, 4 months in polypharmacy, 11 months in medication gaps and 17 days in clozapine over a 5-year period. The majority of transitions were between SGA and medication gap. Accumulated time in medication gaps was seven times as much as in clozapine. Each 10% delay in SGA initiation post-discharge was associated with a 2, 1, and 6% higher risk for polypharmacy (95% CI: 1.01–1.02), gap (95% CI: 1.01–1.01), and clozapine (95% CI: 1.04–1.08), respectively.InterpretationSchizophrenia patients accumulated more time unmedicated and in polypharmacy compared to clozapine. Either treatment guidelines for schizophrenia are not followed, or real-world challenges hamper their implementation.

Incidence of hospital contacts with acute kidney injury after initiation of second-generation antipsychotics in older adults: a Danish population-based cohort study

PurposeTo investigate the association between acute kidney injury (AKI) and use of second-generation antipsychotics (SGA) in older adults.MethodsIn a population-based cohort study using Danish national registries, new users of SGAs (aged ≥ 65) were identified during 2005–2015. Each SGA user was matched to 10 population controls on age, sex, and the SGA initiation date. The outcome was incident AKI within 90 days after the index date. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders.ResultsIn the study, 36,581 new SGA users and 365,810 controls were included. The 90-day incidence rate of AKI was 4.38 and 1.70 per 1000 person-years among SGA users and controls, respectively, corresponding to a crude HR of 2.57 (1.79–3.68). The fully adjusted HR (aHR) was 1.43 (0.89–2.27) for all SGAs. The risk differed among individual drugs with aHRs for olanzapine 3.50 (1.20–10.23), quetiapine 1.62 (0.81–3.26), and risperidone 0.68 (0.28–1.64). In sensitivity analyses, the aHR declined to 1.24 (0.95–1.61) at 1-year follow-up.ConclusionsOlanzapine use was associated with a significantly increased 90-day AKI risk. For quetiapine, the risk was elevated but not significant, and risperidone had no association. CIs were wide and confounder adjustment largely impacted the estimates. Main limitations included residual confounding and incomplete recording of AKI diagnoses.

Subthreshold Change in Glycated Hemoglobin and Body Mass Index After the Initiation of Second-Generation Antipsychotics Among Patients With Schizophrenia or Bipolar Disorder: A Nationwide Prospective Cohort Study in Japan.

Objective: The risk of diabetes development has been reported to differ among second-generation antipsychotics (SGAs). However, few studies have focused on the subthreshold change in glycated hemoglobin (HbA1c). Therefore, this study examined the subthreshold change in HbA1c and change in body mass index (BMI) 3 months after patients initiated one of 6 SGAs widely prescribed in Japan.Methods: This is a prospective cohort study of patients followed up based on the Japanese blood glucose monitoring guidelines for patients with schizophrenia. We collected eligible patients' demographic data, medication history, blood tests, and weight measurements both at baseline and 3 months after recruitment, between April 2013 and March 2015. In the 378 patients with schizophrenia, schizoaffective disorder, and bipolar disorder based on ICD-10, we compared the subthreshold change in HbA1c and the change in BMI 3 months after antipsychotic initiation by using multivariate regression analysis.Results: The subthreshold change in HbA1c 3 months after initiating blonanserin was significantly lower compared with olanzapine (B = -0.17, 95% CI = -0.31 to -0.04). In addition, the change in BMI 3 months after initiating blonanserin and aripiprazole was significantly lower compared with olanzapine (B = -0.93, 95% CI = -1.74 to -0.12; B = -0.71, 95% CI = -1.30 to -0.12, respectively).Conclusions: This is the first study to clarify the differences in the subthreshold change in HbA1c among SGAs. Our results suggest that blonanserin is likely to be a favorable treatment for patients with high risk of diabetes.Trial Registration: UMIN Clinical Trial Registry identifier: UMIN000009868.

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder

BackgroundMany second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk.MethodsPatients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013–February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions.ResultsMedian follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG.ConclusionsIn this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.

The incidence and economic burden of extrapyramidal symptoms in patients with schizophrenia treated with second generation antipsychotics in a Medicaid population

Background Extrapyramidal symptoms (EPS) are common side-effects of second-generation antipsychotics (SGA), that can negatively impact patient quality-of-life, and are associated with increased morbidity and mortality. This study examined the incidence and burden of EPS in patients with schizophrenia initiating SGAs. Methods Patients with schizophrenia initiating SGAs were identified in the MarketScan Multi-state Medicaid database from 1 January 2012 to 31 December 2018. Incidence of EPS (identified via ICD-9/ICD-10 diagnoses and medications) was assessed during the 12-months following SGA initiation. Cohorts with and without EPS were defined. Multivariate models were used to examine all-cause and schizophrenia-related hospitalizations and total costs in the 12 months following the first EPS claim (EPS) or randomly assigned index date (Non-EPS) while controlling for multiple baseline covariates. Logistic regression was used for hospitalization and two-part models were used for skewed cost data. Results A total of 11,642 patients with schizophrenia filled a prescription for an SGA; of which, 2,468 (21.2%) experienced EPS in the first year. The age- and gender-matched EPS group and non-EPS group included 2,295 and 5,607 patients, respectively. Multivariate analyses confirmed that EPS patients had 25% higher odds of all-cause (OR = 1.25; 95% CI = 1.11–1.40) and 75% increased odds of schizophrenia-related (OR = 1.75; 95% CI = 1.53–2.00) inpatient admissions compared to non-EPS patients. Multivariate adjustment of post-period costs between groups also found significant differences in both all-cause (EPS: $27,408 vs. non-EPS: $22,489, p < 0.001) and schizophrenia-related (EPS:$12,833 vs. non-EPS:$8,077, p < 0.0001) costs between the EPS and non-EPS cohorts. Conclusions Over one-fifth of patients initiating treatment with atypical antipsychotics in this study developed EPS in the 12 months following SGA initiation. Extrapyramidal side-effects associated with atypical antipsychotics increase the risk of hospitalization and contribute to higher healthcare costs. For patients with schizophrenia, treatment options that minimize the risk of EPS may reduce the economic burden associated with the disease.

Association of Social Determinants of Health With Adherence to Second-generation Antipsychotics for People With Bipolar Disorders in a Medicaid Population.

About 7 million people, 2.8% of US adults, have bipolar disorder (BD). While second-generation antipsychotics (SGA) are indicated as acute and maintenance treatments for BD, therapeutic success requires medication adherence and reported nonadherence estimates to range as high as 60%. Identifying patient risk factors for nonadherence is important for reducing it. The objective of this study was to quantify the associations of risk factors, including social determinants of health, with SGA nonadherence among patients with BD. In this cross-sectional study of 2015-2017 MassHealth Medicaid data, we examined several definitions of adherence and used logistic regression to identify risk factors for nonadherence (medication possession ratio <0.8) among all adults aged 18-64 diagnosed with BD who could be followed for 12 months following SGA initiation. Among 5197 patients, the mean (±SD) age was 37.7 (±11.4) years, and 42.3% were men. Almost half (47.7%) of patients were nonadherent to SGAs when measured by medication possession ratio. The prevalence of nonadherence peaked at middle age for men and younger for women. Nonadherence was less common among Massachusetts' Department of Mental Health clients (odds ratio=0.60, 95% confidence limit: 0.48-0.74) and among those who used other psychotropic medications (odds ratios between 0.45 and 0.81); in contrast, increase in neighborhood socioeconomic stress was associated with increased odds of nonadherence. Adherence to SGA treatment is suboptimal among people with BD. Recognizing risk factors, including those related to social determinants of health, can help target interventions to improve adherence for people at high risk and has implications for adherence-based quality measures.

Weight Gain and Treatment Interruptions with Second-Generation Oral Antipsychotics: Analysis of Patients with Schizophrenia or Bipolar I Disorder

Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.Funding. Alkermes, Inc.

The Importance of Second-Generation Antipsychotic-Related Weight Gain and Adherence Barriers in Youth with Bipolar Disorders: Patient, Parent, and Provider Perspectives.

Objectives: The objective of this research was to understand physician, patient, and parent perspectives on barriers to second-generation antipsychotic (SGA) medication adherence in youth with bipolar spectrum disorders, and attitudes toward treatment of SGA-related weight gain. Methods: Patients diagnosed with bipolar disorder before age 18, parents of children diagnosed before 18, and clinicians with experience prescribing SGAs for these patients completed surveys regarding SGA-related side effects, adherence barriers, and acceptability of weight management strategies. Results: Patients (n = 225), parents (n = 128), and clinicians (n = 54) reported weight gain as the most concerning SGA-related side effect (45.6%, 38.9%, and 70.4%, respectively). Weight gain was also the top adherence barrier for patients (35.9%), but was ranked fourth (41.8%) by parents. Patients (61.5%) were more likely "definitely" willing to co-initiate another medication to manage weight gain upon SGA initiation than parents (20.1%) or clinicians (1.9%). Conversely, parents (54.9%) and clinicians (84.9%) were "definitely" willing to accept/prescribe a second medication aiming to reverse weight gain of ≥10 lbs., and patients (61.1%) were willing to add another medication to reverse any weight gain. Conclusion: SGA-related weight gain impairs medication adherence in young patients with bipolar disorder. Many young patients would start pharmacologic treatment to mitigate SGA-related weight gain at treatment initiation, parents and clinicians are more hesitant. This research informs patient-centered perspectives on SGA adherence barriers and strategies to minimize potential side effects, which may improve adherence in this vulnerable patient population.

Current follow-up practices often fail to detect metabolic and neurological adverse reactions in children treated with second-generation antipsychotics.

This study examined the use and adverse reactions of second-generation antipsychotics (SGAs), alone or combined with other psychotropic medication, to identify areas for standardising prescribing and monitoring practices. We conducted a retrospective study at Tampere University Hospital, Finland, involving 128 patients (81% boys) who were under 13years old at SGA initiation and had SGA treatment between October 2013 and October 2014. The median age at baseline was 9.4years. Weight gain was reported as an adverse reaction in 33%, but an increase in standardised body mass index, adjusted for age and sex (BMI z-score), was detected in 75% of patients with sufficient data. The statistically significant median changes during the study were an increase of 0.46 in BMI z-score, a reduction of 0.25mmol/L in fasting plasma high-density lipoprotein and an increase of 0.28mmol/L in triglyceride values. The weight gain was most apparent in patients treated with just an SGA or SGA plus melatonin. Patients treated with an SGA plus medication for attention deficit hyperactivity disorder were less likely to gain weight. SGA-induced metabolic disturbances remained partly unrecognised in children under 13years of age and more systematic monitoring is needed.

The impact of depression medications on oral antidiabetic drug adherence in patients with diabetes and depression

AimsTo compare adherence and persistence to oral antidiabetic drugs (OAD) between patients who are new users of second generation antipsychotics (SGA) versus new users of other depression therapies in adults with type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD). MethodsAdults 18–64 years with previously-treated T2DM and MDD (past OAD and SSRI/SNRI use) who are new users of SGA or non-SGA therapies (bupropion, lithium, mirtazapine, thyroid hormone, tricyclic antidepressant) were identified in the 2009–2015 MarketScan® Commercial Claims and Encounters database. Multivariate regression models were used to determine the odds of a ≥10% decline in OAD adherence over 180- and 365-days, and time to OAD discontinuation, adjusting for differences between groups. ResultsA total of 8664 (21.5% SGA), 8311 (22.1% SGA), and 17,524 (21.3% SGA) patients met inclusion criteria for the 180-day adherence, 365-day adherence, and persistence cohorts, respectively. Over 180-days, 16.6% of SGA and 13.3% of non-SGA initiators had a ≥10% decline in OAD adherence (adjusted odds ratio [OR] = 1.41, 95% CI 1.21–1.63). Over 365-days, 22.3% of SGA and 18.9% of non-SGA initiators had a ≥ 10% decline (OR = 1.34, 95% CI 1.17–1.53). Time to OAD discontinuation was similar between groups (adjusted hazard ratio = 1.03, 95% CI 0.94–1.12). ConclusionUse of SGA was associated with a 1.3–1.4 times higher odds of a ≥10% decline in OAD adherence. Adherence to OAD is critical for optimal diabetes control and reductions in this magnitude may impact A1C. Close monitoring of OAD adherence after SGA initiation is warranted.

Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Pharmacotherapy for posttraumatic stress disorder at a Veterans Affairs facility.

Results of a study of psychotropic prescribing patterns in a Veterans Affairs (VA) population with posttraumatic stress disorder (PTSD) are presented. VA prescription records were reviewed to identify veterans with PTSD at a large VA healthcare center and evaluate their medication regimens for conformance with a VA practice guideline that calls for the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line therapies for PTSD; the VA guideline does not recommend second-generation antipsychotics (SGAs) and benzodiazepines for PTSD symptom control. The primary objective was to determine if veterans with PTSD who were receiving an SGA had first received SSRI or SNRI therapy in accordance with VA recommendations. Among 308 veterans who met the inclusion criteria, the average number of SSRI or SNRI agents prescribed prior to initiation of SGA therapy was 0.88. Only 19.8% of patients (n = 61) had been prescribed 2 SSRI or SNRI agents, with 48.4% of patients (n = 149) having received 1 agent. All evaluated courses of SSRI and SNRI therapy prior to SGA initiation were of sufficient duration (range, 5-30 months), and mean adherence rates were >80%. Current or past benzodiazepine use was documented in about 55% of patients (n = 170). SSRIs and SNRIs were under-utilized for the treatment of PTSD at the study site in patients receiving an SGA. The current use of benzodiazepines in these patients was lower than a reported national average for VA patients.

Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths.

Second-generation antipsychotics (SGAs) have increasingly been prescribed to Medicaid-enrolled children, either singly or in a medication combination. Although metabolic adverse effects have been linked to SGA use in youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has been challenging. To determine whether SGA initiation was associated with an increased risk for incident type 2 diabetes mellitus. Secondary analyses examined the risk associated with multiple-drug regimens, including stimulants and antidepressants, as well as individual SGAs. Retrospective national cohort study of Medicaid-enrolled youths between January 2003 and December 2007. In this observational study using national Medicaid Analytic eXtract data files, initiators and noninitiators of SGAs were identified in each month. Included in this study were US youths aged 10 to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for-service arrangement during the study. Those with chronic steroid exposure, a diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were ineligible. The mean follow-up time for all participants was 17.2 months. Youths were followed up until diagnosis of diabetes mellitus or end of follow-up owing to censoring caused by the transition into a Medicaid managed care arrangement or Medicaid ineligibility (the end of available data). Propensity weights were developed to balance observed demographic and clinical characteristics between exposure groups. Discrete failure time models were fitted using weighted logistic regression to estimate the risk for incident diabetes mellitus between initiators and noninitiators. A filled SGA prescription. Incident type 2 diabetes mellitus identified through visit and pharmacy claims during the observation period. Among 107,551 SGA initiators and 1,221,434 noninitiators, the risk for incident diabetes mellitus was increased among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared with youths initiating only SGAs, the risk was higher among SGA initiators who used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95% CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators who were concomitantly using stimulants. As compared with a reference group of risperidone initiators, the risk was higher among those initiating ziprasidone (OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21-2.07; P = .001) but not quetiapine fumarate or olanzapine. The risk for incident type 2 diabetes mellitus was increased among youths initiating SGAs and was highest in those concomitantly using antidepressants. Compared with risperidone, newer antipsychotics were not associated with decreased risk.

Metabolic monitoring for youths initiating use of second-generation antipsychotics, 2003-2011.

In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years. Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis. The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern. The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

Patterns of initiation of second generation antipsychotics for bipolar disorder: a month-by-month analysis of provider behavior

BackgroundSeveral second generation antipsychotics (SGAs) received FDA approval for bipolar disorder in the 2000s. Although efficacious, they have been costly and may cause significant side effects. Little is known about the factors associated with prescribers’ decisions to initiate SGA prescriptions for this condition.MethodsWe gathered administrative data from the Department of Veterans Affairs on 170,713 patients with bipolar disorder between fiscal years 2003–2010. Patients without a prior history of taking SGAs were considered eligible for SGA initiation during the study (n =126,556). Generalized estimating equations identified demographic, clinical, and comorbidity variables associated with initiation of an SGA prescription on a month-by-month basis.ResultsWhile the number of patients with bipolar disorder using SGAs nearly doubled between 2003 and 2010, analyses controlling for patient characteristics and the rise in the bipolar population revealed a 1.2% annual decline in SGA initiation during this period. Most medical comorbidities were only modestly associated with overall SGA initiation, although significant differences emerged among individual SGAs. Several markers of patient severity predicted SGA initiation, including previous hospitalizations, psychotic features, and a history of other antimanic prescriptions; these severity markers became less firmly linked to SGA initiation over time. Providers in the South were somewhat more likely to initiate SGA treatment.ConclusionsThe number of veterans with bipolar disorder prescribed SGAs is rising steadily, but this increase appears primarily driven by a corresponding increase in the bipolar population. Month-by-month analyses revealed that higher illness severity predicted SGA initiation, but that this association may be weakening over time.

Effectiveness of an educational handbook in improving psychiatry resident knowledge of second-generation antipsychotics.

The authors describe a pilot evaluation of an educational handbook designed to increase resident knowledge of second-generation antipsychotic (SGA) use in the pediatric population, with an emphasis on metabolic monitoring. An educational handbook focusing on SGA use in children and adolescents was introduced to psychiatry residents undergoing a child psychiatry rotation. Baseline and post-intervention questionnaires were administered to determine whether SGA knowledge increased. Baseline and post-intervention questionnaires were completed by 32 residents. At baseline, most residents (92.9 %) had interacted with an adult patient requiring an SGA and had prescribed SGAs at least five times (70.9 %) in the previous month. Baseline SGA knowledge was limited such that only 5.4 % of participants scored greater than 80 %, and 28.6 % scored below 60 %. Mean total score improved significantly from pre-test (18.4 ± 4.23) to post-test (21.2 ± 3.28, p = 0.001). Stratified analysis suggested a significant improvement of scores (post-test versus pre-test, respectively) in females (21.8 ± 3.11 versus 18.0 ± 4.94, p = 0.003) and junior residents (21.3 ± 3.34 versus 18.1 ± 4.37, p = 0.001). While significant improvements were documented in questions related to Health Canada-approved and other off-label evidence-based indications, and the appropriate physical examination components and laboratory tests to perform at SGA initiation and follow-up, no improvements were documented regarding the distinguishing properties, side effects, and appropriate history-taking prior to SGA initiation. Implementation of an educational handbook can improve resident knowledge related to SGA use in children over the short-term. However, future research should be directed at the effectiveness of more interactive web-based formats in optimizing learning for male residents and ensuring more comprehensive knowledge uptake. While the introduction of an education handbook is the first step in addressing some of the barriers to metabolic monitoring, prospective longitudinal studies are required to determine whether such an intervention will ultimately improve prescriber adherence over the long-term.

Characteristics and trends of low‐dose quetiapine use in two western state Medicaid programs

Medicaid programs are concerned about inappropriate, potentially hazardous, and costly off-label use of second-generation antipsychotics (SGAs). Several states are exploring policies aimed at managing low-dose quetiapine, commonly prescribed for off-label conditions. This study aimed to characterize longitudinal trends and patient characteristics associated with low-dose quetiapine in two state Medicaid programs. We further aimed to quantify changes in the use of quetiapine associated with a legal settlement that curtailed off-label promotion of this product. Using administrative data from two state Medicaid programs, Oregon and Colorado, we identified SGA initiators and determined patient level factors associated with receipt of low-dose SGAs. We evaluated changes in low-dose quetiapine initiation during and after a period in which quetiapine was being promoted illegally for off-label purposes. We identified 14,763 new SGA starts during the study period. Low-dose (versus therapeutic dose) SGA use was common in both states, representing 53% to 56% of initiators. Quetiapine was the most commonly used SGA in both states and both dose ranges. Diagnoses of schizophrenia, bipolar disorder, posttraumatic stress disorder, anxiety disorder, and use of newer sedative hypnotics were associated with lower likelihood of initiating low-dose quetiapine. Initiation of low-dose quetiapine as a proportion of all SGA initiation and of all quetiapine initiation significantly declined in Oregon following suspension of off-label promotional activities. Low-dose SGA and specifically low-dose quetiapine use remains common. Medicaid programs must set policies carefully to maximize the net safety of prescription use while optimizing disease management considering the potential for substitution effects.

Surveillance métabolique biologique après initiation d’un traitement antipsychotique chez des personnes traitées par lithium ou anticonvulsivants

To assess the rate of metabolic testing after initiation of second-generation antipsychotics (SGA) prescription in persons initially treated by conventional mood-stabilizers (lithium or anticonvulsants, as a proxy of bipolar disorder diagnosis) and to compare the rates of metabolic testing in these persons with those in persons with initiation of first-generation antipsychotics (FGA) prescription or with no antipsychotic prescription. Data were anonymously extracted from the 2004 to 2006 French national health database of the Régime Social des Travailleurs Indépendants (RSI). Patients aged 18 years and over were included in the cohort if they fulfilled the following criteria over a three-month inclusion period: refunding of lithium or anticonvulsant over the 3 months without discontinuation (as a proxy of bipolar disorder diagnosis), no concomitant refunding over the 3months of antipsychotic, and no concomitant refunding over the 3 months of an anti-diabetic drug (as a marker of diabetes) or a lipid-lowering drug (as a marker of hyperlipidemia). Metabolic testing was assessed using information collected in the RSI database on the reimbursement of glucose-specific serum tests (glycaemia) and lipid-specific serum tests (total cholesterol). Serum glucose and lipid testings were assessed at baseline and at 12-week follow-up for the first episode of antipsychotic dispensing. Multivariate analyses were performed to compare the rate of metabolic testing in users of SGA to those of users of FGA and to those of non-users of antipsychotics. Three thousand one hundred and seventy patients were included. Of the 490 (15.4%) persons with a first episode of antipsychotic dispensing after the index date, 138 (4.3%) were dispensed only FGA over the first episode and 352 (11.1%) SGA (including 37 patients with both SGA and FGA dispensing). Metabolic testing at baseline and at 12-week follow-up was performed for 14% of persons with initiation of FGA and 12% with initiation of SGA. Almost no patient had both baseline and follow-up testing. Testing rates were lower for lipid testing than for glucose testing. Compared to persons with no antipsychotic, persons with SGA were significantly more likely to have metabolic testing at baseline and at follow-up, independently from other characteristics (adjusted OR=0.24, 95% CI 0.16 to 0.36). No difference was found between persons with SGA and those with FGA (adjusted OR=1.12, 95%CI 0.62 to 2.0). Regarding the other characteristics associated with likelihood of metabolic testing (irrespective of the treatment group), women were more likely than men to have metabolic testing at baseline but not at follow-up. Elderly persons and persons with low occupational status were more likely to have metabolic testing at follow-up. From a public health point of view, such findings indicate that the metabolic risks associated with SGA use in real-life conditions are widely underestimated. Regarding the temporal trends of antipsychotic prescription, with the dramatic rise of SGA use observed in most countries, it is a public health priority to improve metabolic monitoring in SGA users, irrespective of the underlying diagnosis. Since it is more complex to modify pre-existing inadequate practices than to initiate correct ones in new prescribers, great attention should be paid to the need for delivering strong messages regarding the metabolic risks associated with SGA prescription during the initial training of physicians.