Second-generation Antipsychotics Therapy Research Articles

Medication compliance in outpatients with schizophrenia in one veterans hospital in Taiwan

Medication compliance is an important determinant in schizophrenia treatment outcomes. This study aimed to investigate medication compliance in cases of patients receiving a single antipsychotic medication among adult outpatients with schizophrenia, and examine whether their antipsychotic therapy and other factors may affect the medication compliance. Subjects with schizophrenia who had received any single outpatient first- or second-generation antipsychotic therapy from the Yuli Veterans Hospital, Taiwan, during August and November 2006 were identified from medical chart reviews. The selected subjects were surveyed for information including their medication compliance, sociodemographics, treatment-related side effects, social support, and perceived treatment-related benefits. Their physicians were also surveyed on their medication compliance, Clinical Global Impression (CGI) scores, and comorbid mental illness(es). Good medication compliance was defined as consumption of more than 75% of prescribed antipsychotics in the previous month. Subjects were categorized into this group when both their self-reported consumption and their physicians' estimation were higher than 75%. A logistic regression model was adopted to evaluate the association of each factor with medication compliance. Of the 76 subjects surveyed, 39 (51%) received second-generation antipsychotics (amisulpride, risperidone, or olanzapine), while 37 (49%) received first-generation antipsychotics (haloperidol or sulpiride). Thirty-eight (50%) consumed more than 75% of prescribed medications in the previous month. The average age was 41, and 62% of the sample was male. Education level and employment type were significantly different between individuals with good and poor medication compliance. The regression result indicated that education of above nine years was significantly associated with an increased likelihood of good medication compliance. Employment and perceived treatment benefits were marginally significantly correlated with good medication compliance. Second-generation antipsychotics, however, had no correlation with good medication compliance.

Metabolic monitoring of second-generation antipsychotics: Evaluation of a pharmacist- and nurse-driven protocol

ObjectiveSecond-generation antipsychotic therapy can lead to metabolic abnormalities, increasing the risk of cardiovascular disease and death in patients with serious mental illness. However, the literature suggests there is a lack of appropriate monitoring in individuals receiving these therapies. This study aims to evaluate whether the implementation of a pharmacist- and nurse-driven metabolic monitoring protocol will increase monitoring in patients prescribed second-generation antipsychotic therapy in an outpatient community mental health clinic. MethodsA retrospective review of adult outpatients in a community mental health clinic who were prescribed second-generation antipsychotics was conducted from October 1, 2017, to March 31, 2019. Pre- and postprotocol implementation groups were compared to assess the impact of the protocol on the primary outcome of appropriateness in monitoring for metabolic parameters. ResultsA total of 160 patients who met the inclusion criteria were randomly selected and reviewed, allowing for 80 individuals in each group. Improvement in the appropriateness of monitoring was found for 4 of 5 metabolic parameters after protocol implementation, including blood pressure (17.5% to 43.8%, P < 0.001), weight (17.5% to 43.8%, P < 0.001), hemoglobin A1C (27.5% to 42.5%, P = 0.044), and lipid levels (17.5% to 31.3%, P = 0.04). Primary care physicians ordered most of the laboratory values (44.5% to 46.2%); however, pharmacists and nurses ordered 7% of laboratory tests after the protocol implementation. ConclusionDespite the knowledge that second-generation antipsychotic therapies commonly lead to metabolic syndrome and therefore increased cardiovascular disease risk, monitoring for metabolic effects remains poor, and there is a lack in diversity of strategies to improve this monitoring. Although further research on the effectiveness of a pharmacist- and nurse-driven metabolic monitoring protocol in this setting is warranted, this protocol serves as an example of a novel strategy with the potential to improve metabolic monitoring of second-generation antipsychotic therapy.

1258-P: Lack of Monitoring for Glucose Intolerance in Overweight and Obese Youth on Second-Generation Antipsychotics Despite Increased Risk

Second-generation antipsychotics (SGAs) increase risk for glucose intolerance in adults; less is known about risk in youth. MOBILITY is a large, multi-center, pragmatic study designed to assess the effect of metformin added to a lifestyle intervention compared to lifestyle alone on weight gain and metabolic parameters in overweight and obese pediatric (ages 8-19) patients with bipolar-spectrum disorders (BSD) receiving SGAs. Frank diabetes was an exclusion criterion. It was recommended to obtain baseline, +6 month, and +12 month fasting metabolic labs in this trial conducted in real-world psychiatry clinics. We estimated prevalence of glucose intolerance prior to intervention. We hypothesized that youth with elevated fasting plasma glucose (FPG) and hemoglobin A1C (HbA1C) would be more likely to have repeat metabolic assessment. Altogether, 684 youth (mean age=14.3 years, 53% male, 64% with baseline BMI ≥95th%ile) were included in these analyses. Baseline FPG was obtained in 73% (501/684); 12.1% of these had impaired fasting glucose (IFG). Baseline HbA1C was obtained in 53% (360/684); 11.1% had HbA1C ≥5.7%. Six patients (1.6%) had both measures elevated. Only 41% of patients with IFG and 40% of those with HbA1C ≥5.7% had repeat glucose measures within 1 year; neither were more likely to have repeat laboratory testing than patients with normal baseline laboratory results (OR=0.88, p=0.773; OR=0.85; p=1.00, respectively). Of six patients with both IFG and HbA1C elevated at baseline, only three had repeat laboratory testing; one of these developed diabetes on follow-up. Overweight and obese youth with BSD on SGA therapy have clinically relevant rates of glucose intolerance. However, assessment and, especially, reassessment of abnormal glucose status in this population is poor. Further studies are needed to identify and address barriers for evaluation for glucose intolerance in this at-risk population. Disclosure N.A. Crimmins: None. M.P. DelBello: None. C. Correll: Consultant; Self; Alkermes plc., Allergan plc., Janssen Pharmaceuticals, Inc., Lundbeck, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Sumitomo Dainippon Pharma Co., Ltd., Sunovion Pharmaceuticals Inc., Takeda Pharmaceutical Company Limited, Teva Pharmaceutical Industries Ltd. C. Klein: None. T. Blom: None. J. Welge: None. Funding Patient-Centered Outcomes Research Institute (to M.P.D.)

Second-generation long-acting injections anti-psychotics improve executive functions in patients with schizophrenia: a 12-month real-world study

Background: The main purpose of this study was to assess possible modifications of cognitive performance among schizophrenia patients treated with long-acting injectable antipsychotics (LAIs) of second generation anti-psychotics (SGAs). Our hypothesis is that the shift from the oral formulation to the LAI formulation of SGAs drugs improves the cognitive performance. The secondary objective was to carry out a head to head comparison of two different SGA-LAI treatments [i.e., 1-month Paliperidone Palmitate (PP1M), monthly Aripiprazole (Ari-LAI)] in our study with an independent and real-world setting.Methods: The sample comprised 32 participants who were consecutively recruited over 12 months. Seventeen patients treated with Ari-LAI and 10 treated with PP1M completed psychopathological, neuropsychological and functional assessments. Group differences were explored through chi-squared and t-tests, as appropriate. GLM Repeated Measures were used to study variations of cognitive performance along 12 months and to test differences between drugs.Results: We found an effect of time on the outcomes investigated but this did not depend on the type of LAI used.Conclusions: In comparison with the previous oral treatment with SGAs, patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI. Furthermore, there were no differences between the SGA-LAI regimens.Key pointsThe main purpose of this study was to assess possible modification of cognitive performance of patients with Schizophrenia treated with second generation long-acting injectable antipsychotics (SGA-LAIs).The secondary objective was to carry out a head to head comparison of two different SGA-LAIs: Paliperidone Palmitate 1-Month (PP1M) and Aripiprazole Monthly (Ari-LAI).Patients showed a significant improvement in neurocognitive function after 12 months of treatment with SGA-LAI.There were no differences between the SGA-LAI regimens.From a practical point of view, switching to LAI formulation seems to produce further social and cognitive improvements in patients who had already benefitted from oral SGA therapy.

The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population.

Objectives: The aim of this study was to determine the incidence of metabolic syndrome in patients treated with second-generation antipsychotics (SGAs). Methods: In this retrospective study, we reviewed patients’ electronic medical records (EMRs) of all patients who received one SGA for at least six months, excluding patients who were taking other medications that are associated with significant effect on metabolic syndrome. Relevant clinical information was collected prior to starting the SGA and after six months of continuous use of the same SGA. Results: A total of 91 patients were included in the study. The majority of patients (72%) were diagnosed with schizophrenia. After six months of taking the SGA, 44% of patients experienced elevated systolic pressure, 54.9% had elevated triglyceride, and 31.9% had impaired glucose levels (p value < 0.05). Prior to initiating SGA therapy, 14.3% of patients had metabolic syndrome, while 37.4% had metabolic syndrome after six months of therapy, and it was more prominent in males compared to female patients (p value < 0.05). Conclusion: This study found a strong correlation between SGA use and the appearance of metabolic alterations, such as weight gain, glucose intolerance, and increased triglyceride levels. These findings highlight the importance of assessing metabolic deregulations to minimize SGA associated metabolic abnormalities.

Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated with Second-Generation Antipsychotic-Induced Weight Gain

Weight gain is a limiting and frequent adverse effect of second-generation antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy. 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. 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). 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.

Monitoring of Recommended Metabolic Laboratory Parameters Among Medicaid Recipients on Second-Generation Antipsychotics in Federally Qualified Health Centers.

In 2004, a consensus statement outlining recommended metabolic monitoring for patients prescribed second-generation antipsychotics (SGAs) was published. More than a decade later, suboptimal adherence rates to these recommendations continue to be reported, which could lead to long-term and costly complications. To define the prevalence of appropriately monitored Medicaid patients receiving care at federally qualified health centers (FQHCs) prescribed SGAs. This was a retrospective study examining electronic health record and Medicaid claims data to assess the rates of glucose and lipid monitoring for patients prescribed SGAs from January 2014 to August 2016 in a FQHC. Prescription and laboratory claims for patients receiving care at 4 FQHCs were reviewed. Descriptive statistics were used to evaluate the primary outcome. A total of 235 patients were included in the analysis. Patients initiated on SGA therapy (n = 92) had baseline glucose and lipid monitoring rates of 50% and 23%, respectively. The 3-month monitoring rates were 37% for glucose and 26% for lipids, whereas annual rates were 71% and 40%, respectively. Patients continuing SGA therapy (n = 143) had annual glucose and lipid monitoring rates of 67% and 44%. Medicaid patients at FQHCs initially prescribed SGAs have low baseline and 3-month metabolic monitoring, whereas annual monitoring was comparable to previously published studies. Adults receiving chronic care at a FQHC were more likely to receive glucose monitoring. Those with type 2 diabetes mellitus and/or hyperlipidemia were more likely to receive glucose and lipid monitoring.

The influences of antipsychotics therapy at cognitive impairments in schizophrenia spectrum disorders

Significant degree of cognitive impairment represents one of the basic cornerstones among clinical manifestations of the schizophrenia spectrum disorders and accordingly to some authors it is present in up to 75% patients with these syndromes. The aim of this study was to examine degree of cognitive impairment, firstly among patients on first generation antipsychotics therapy (FGA) compared to the patients on second generation antipsychotics therapy (SGA), and secondly to compare both groups of patients with healthy controls.Material and methodsProspective, parallel research was conducted, in which the sample of patients and employees of Specialized Psychiatric Hospital Kotor was tested with Montreal Cognition Scale (MoCA). There were 66 participants in the samples and they were divided on four subgroups: (1) patients with FGA; (2) patients with SGA; (3) patients with combined FGA and SGA; (4) Healthy controls.ResultsAll groups of patients had statistically significantly lower mean MoCA scores in the comparison with healthy controls. The fact that among 83.7% of patients was diagnosed significant degree of cognitive decline (MoCA score bellow 26) strongly speaks in favour of high sensitivity of MoCA test in detection of cognitive impairment among patients with schizophrenia spectrum psychotic disorders. In addition, the group of patients with FGA also had statistically significantly lower mean MoCA score compared to patients with SGA.DiscussionThe mechanisms of explanation of these results can be additionally enlightened with further studies on larger samples of patients, which would investigate the correlation between extrapyramidal symptomatology, anticholinergic therapy and cognitive deficit.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Medication Adherence and Persistence in Patients with Severe Major Depressive Disorder with Psychotic Features: Antidepressant and Second-Generation Antipsychotic Therapy Versus Antidepressant Monotherapy.

Major depressive disorder with psychotic features, or psychotic depression, is a severe mental health disorder often associated with a worse depression-related symptom profile when compared with major depressive disorder without psychotic features. While combination pharmacotherapy with an antidepressant and an antipsychotic is recommended as first-line therapy, antidepressant monotherapy has been found to be useful and efficacious in psychotic depression. To assess the rates of antidepressant adherence and antidepressant persistence in Texas Medicaid patients with psychotic depression who used antidepressant plus second-generation antipsychotic (AD/SGA) therapy or antidepressant (AD) monotherapy. Using Texas Medicaid prescription and medical claims data from September 2007 to December 2012, adult patients aged 18-63 years were included if they had no confounding psychiatric disorders, no antidepressant claims during a 6-month pre-index period, and at least 1 diagnosis for severe major depressive disorder with psychotic features (ICD-9-CM codes 296.24 and 296.34). The first claim date for an antidepressant served as the index date. All patients were required to have at least 2 antidepressant claims, and those in the AD/SGA cohort were required to have 2 or more claims for an SGA. Study covariates included age, gender, race/ethnicity, residence, Charlson Comorbidity Index (CCI) score, and tobacco use/dependence. Statistical analyses included descriptive statistics, univariate analyses, logistic regression, and Cox proportional hazards regression. A total of 926 patients met study criteria (AD cohort = 510; AD/SGA cohort = 416). The overall sample had a mean [±SD] age of 40.5 [±13.2] years and was primarily female (66.8%) and non-Caucasian (74.8%). When compared with the AD cohort, patients in the AD/SGA cohort had a 52.3% higher likelihood of being adherent to antidepressant therapy based on proportion of days covered (PDC; OR = 1.523; 95% CI = 1.129-2.053; P = 0.006). Similarly, antidepressant adherence was 42.0% higher for the AD/SGA cohort based on medication possession ratio (MPR; OR = 1.420; 95% CI = 1.062-1.898; P = 0.018). Younger patients, African Americans, and tobacco users/dependents had significantly worse likelihoods of antidepressant medication adherence based on PDC and MPR. The risk of antidepressant nonpersistence was 23.2% lower for patients in the AD/SGA cohort (HR = 0.768; 95% CI = 0.659-0.896; P = 0.001), compared with those in the AD cohort. Antidepressant nonpersistence was significantly higher in younger patients, African Americans, Hispanics, and tobacco users/dependents. Better antidepressant adherence and persistence outcomes were associated with combination pharmacotherapy with an AD and an SGA antipsychotic. This study provides real-world estimates that support the current first-line treatment recommendations for psychotic depression; however, it should be noted that the majority of study patients used AD therapy only. Future research in psychotic depression is needed. Kim-Romo received funding to conduct this study from the PhRMA Foundation Pre-Doctoral Fellowship in Health Outcomes. Rascati, Richards, Ford, Wilson, and Beretvas declare no conflict of interest in relation to this manuscript. Kim-Romo and Rascati collaborated on the study design, data analysis, study interpretation, and writing of this manuscript. Richards, Ford, Wilson, and Beretvas provided critical evaluation of the study design, analysis, and interpretation, as well as edited this manuscript.

Persistence of metabolic monitoring for psychiatry inpatients treated with second-generation antipsychotics utilizing a computer-based intervention.

Monitoring and intervention for metabolic abnormalities secondary to second-generation antipsychotics (SGAs) remain weak areas of performance in mental health care. This study evaluated the sustained impact of a computerized physician order entry (CPOE) pop-up alert designed to improve rates of laboratory metabolic monitoring of patients treated with SGAs in an inpatient psychiatry unit. Interventions carried out by the psychiatry team to manage metabolic abnormalities found on screening were also identified. A retrospective chart review of patients treated with scheduled SGAs at a large Midwestern academic medical centre's inpatient adult psychiatry unit was conducted nearly 4 years after the initial implementation of a pop-up alert. Rates of laboratory monitoring (blood glucose level, haemoglobin A1C [HbA1c], lipid panel) were compared to those following the initial implementation. Medical charts of patients with abnormal laboratory results were also reviewed to summarize interventions made by the psychiatry team to manage identified abnormalities. Patient demographics in the current study population (n = 129) were similar to those in the initial test cohort (n = 157). There was no significant decrease in monitoring of glucose levels and lipid panels (fasting or random). Nine patients with abnormally elevated laboratories were identified. Interventions by the psychiatry team included referrals to appropriate healthcare professionals and initiation of medication. The rate of metabolic monitoring for inpatients on SGA therapy did not significantly change over time with the continued use of the CPOE pop-up alert. Optimal monitoring utilizing a CPOE pop-up alert may allow the psychiatry team, including psychiatric pharmacists, to better manage metabolic conditions.

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.

Some side effects and effcts on physical activity of second-generation antipsychotics: A study in children and adolescents.

Background:This study was designed to investigate the metabolic adverse effects (AEs) of second-generation antipsychotics (SGAs) and their relationship with physical activity and non-metabolic AE in children and adolescents.Materials and Methods:After exclusion of patients with metabolic syndrome, 62 patients (34 children, 28 adolescents) of both genders who were candidates for SGA therapy were selected. Metabolic parameters included fasting blood glucose (FBG), triglyceride (TG), blood pressure (BP), and waist circumference (WC); non-metabolic AEs and physical activity were evaluated at baseline, 1 month, and 3 months after starting the treatment.Results:Mean of post-treatment FBG and TG were significantly higher than the baseline values (P < 0.0001). Compared to the baseline value, significantly more patients developed abnormally high (AbH) FBG at the end point (P = 0.02). There was no significant difference in the frequency of patients with AbH-FBG either at the baseline or at the end point (P > 0.05). The frequency of patients with AbH-TG at the end point was not significantly higher than those with baseline AbH-TG (P = 0.10). Although no patient was obese at baseline, 11 (18%) patients developed abdominal obesity at the end point (P < 0.0001). There was no significant difference in the frequency of non-metabolic AE (P > 0.05). There was no significant correlation between metabolic and non-metabolic AE (P > 0.05). Frequency of inactive patients was significantly more than the baseline value (P-0.008), and abdominal obesity was significantly more prevalent in less active participants (P = 0.03).Conclusion:The present study showed the AE of SGA on FBG and TG, but no effect on BP and WC. We also found that children are more prone to develop abnormally high FBG.

Second-generation antipsychotics in the treatment of major depressive disorder: current evidence

Major depressive disorder (MDD) is a chronic and recurrent mental condition leading to huge impacts on direct and indirect personal and public medical costs. To overcome such a serious mental disorder, we currently have a number of different classes of antidepressants, such as selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, noradrenergic and specific serotonin receptor antagonists, dopamine and norepinephrine reuptake inhibitors, along with newly introduced antidepressants (e.g., vilazodone and agomelatine). However, a number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that only a third of such MDD patients remit following adequate antidepressant treatment, while most MDD patients suffer from significant core depressive or residual symptoms during their clinical course. There have been some treatment approaches to overcome such a shortage of antidepressant efficacy, such as augmentation of psychotropics other than antidepressants, switching to a different antidepressant and combinations of different antidepressants. Among these different second treatment options, augmentation treatment has some favorable points compared with the combination and switching option (e.g., maintaining previous antidepressant partial response, synergistic effect between different pharmacological profile and no need to wash out previous antidepressants). Recently, second-generation antipsychotics (SGAs), olanzapine plus fluoxetine, quetiapine extended release and aripiprazole have clearly demonstrated efficacy in the treatment of MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials. Eventually, in November 2007, aripiprazole was the first approved by the US FDA as an adjunctive treatment to antidepressants for treating MDD, followed by the approval of quetiapine and olanzapine plus fluoxetine at 2009. This comprehensive review provides an overview of the clinical trial data of SGAs for treating MDD and clinical issues raised in the use of SGA therapy in patients with MDD in clinical practice.

Association Between Second-Generation Antipsychotics and Changes in Body Mass Index in Adolescents

To assess the association of second-generation antipsychotics (SGAs) with changes in body mass index (BMI) among adolescents compared with a matched untreated comparison group. A retrospective cohort study was conducted using an electronic medical record database between January 2004 and July 2009. Adolescents (12-19 years old), newly initiated on SGAs formed the exposure group and untreated adolescents formed the comparison group matched (3:1) to the antipsychotic group based on age, gender, and month of index SGA. Both the exposure and comparison groups were followed for slightly more than a year (395 days). Baseline and follow-up BMI were evaluated for both groups and percentage change from baseline BMI to follow-up BMI was calculated. Multivariate linear regression was conducted to assess the impact of SGAs on percent change in follow-up BMI from baseline controlling for demographic characteristics, baseline medications, comorbidities, and other covariates. The mean percentage increase in follow-up BMI from baseline for antipsychotic group was significantly higher than the comparison group (p < .01). After adjusting for covariates, adolescents on olanzapine had the highest percentage increase in follow-up BMI from baseline (5.84%, 95% confidence interval [CI], 4.07-7.61) followed by aripiprazole (4.36%; 95% CI, 3.08-5.64), risperidone (3.65%; 95% CI, 2.61-4.68), and quetiapine (1.53%; 95% CI, .53-2.52) compared with the comparison group. This study further validates a growing concern of increased BMI in adolescents on SGA therapy.

Clinician Education Improves Lipid Monitoring in Patients Taking Second-Generation Antipsychotic Agents, Nationally and Locally

BackgroundContinuing medical education (CME) seeks to improve patient health by promoting clinician practice change. Many patients with a diagnosis of either bipolar disorder or schizophrenia are predisposed to cardiovascular risk, and the use of second-generation antipsychotic (SGA) medications that can cause significant weight gain and altering of lipid profiles may compound this risk. An educational analysis identified a performance gap related to psychiatrists' gathering of baseline lipid data in their patients. ObjectiveThis study analyzes the degree to which participation in 2 CME activities improves clinicians' rates of lipid monitoring in patients with mental illness who take SGAs. Study DesignAfter participation in 1 or 2 CME activities on improved cardiometabolic monitoring in patients with major mental illness—in which one activity focused on schizophrenia and the other on bipolar disorder—a nationwide group (NG) of clinician learners was surveyed about lipid monitoring practices among patients during these patients' first 16 weeks of SGA therapy over a 12-month period. Responses from the NG were compared with those from 1) a nationwide control group (CG) and 2) a local group of activity participants at the Lindner Center of HOPE—Cincinnati, Ohio (LG), whose measured rates were documented via medical records data extraction; the LG also received institutional encouragement and support for practice change for lipid monitoring in these patients. ResultsPercentages of patients monitored by clinicians in the NG increased by 18.0 percentage points over 1 year from baseline (P=0.00001) and represented a rate change that was higher than that seen in the CG (P < 0.00001). Gross, median monitoring rates in the NG increased from 27.5% to 80.0%, and all clinicians at or above the 75th percentile of monitoring rates monitored 100% of their patients after participating. Monitoring rate increases for clinicians in the NG were greater among clinicians with higher patient counts. The LG saw a 28 percentage-point increase (from 27.5% to 55.5%), representing a 102% increase over the baseline LG rate and a 56% increase over the rate change seen in the NG. ConclusionsCME interventions can improve lipid-monitoring practices among clinicians who treat patients with major mental illness who take SGAs. Local, institutional support for guideline-recommended monitoring may increase nationwide CME-induced change yet further.

Inconsistent Data Link Antipsychotic Use, Diabetes

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessInconsistent Data Link Antipsychotic Use, DiabetesLeslie SinclairLeslie SinclairSearch for more papers by this authorPublished Online:20 Jan 2012https://doi.org/10.1176/pn.47.2.psychnews_47_2_22-aAbstractDo second-generation antipsychotic medications cause diabetes in children and adolescents? That’s the question a team of researchers based at the Meyers Primary Care Institute of the University of Massachusetts School of Medicine recently sought to assess.“Numerous case reports and studies have suggested a link between the use of antipsychotic medications and diabetes mellitus, impaired glucose tolerance, and insulin resistance in adult populations, although the evidence has been inconsistent,” said Susan Andrade, Sc.D., a senior research associate at the Meyers Primary Care Institute and a research associate professor of medicine at the University of Massachusetts Medical School, and colleagues. Their results were published in the December 2011 Pediatrics.Is there a link between diabetes and the use of antipsychotic medications in children? The jury is still out.Credit: jordache/ ShutterstockIn light of dramatic increases in use of second-generation antipsychotics in children and adolescents, Andrade and colleagues evaluated the risk of incident diabetes mellitus associated with the use of these medications in a large diverse cohort of children who had received treatment in a typical clinical practice.To do so, they conducted a retrospective study using the administrative databases of three health plans participating in the Health Maintenance Organization Research Network. Children aged 5 to 18 who began second-generation antipsychotic therapy from January 2001 through December 2008 were compared with two control groups: nonusers of psychotropic drugs and users of antidepressant medications. “This approach allowed us to select children more likely to be similar to second-generation antipsychotic users in terms of treatment for mental health conditions and the potential for detection/diagnosis of diabetes,” explained the researchers. Diagnoses from inpatient and outpatient records, pharmacy dispensings, and outpatient laboratory results were used to identify incident cases of diabetes.Looking at information on more than 9,000 children who had received second-generation antipsychotics, and comparing them with more than 38,000 who had received no psychotropics, and more than 26,000 who had received antidepressants, the researchers found their results to be inconsistent.A total of 57 children were identified as having incident diabetes during the follow-up period. “The findings differed depending on the comparison group and the definition of the outcome of interest,” the researchers noted. “We found a potentially fourfold increased rate of diabetes among children exposed to second-generation antipsychotics in comparison with children not exposed, but no statistically significantly increased rate in comparison with children exposed to antidepressant medication.”The researchers also noted the existence of previous evidence suggesting that youths receiving second-generation antipsychotics experience adverse changes in body composition and metabolic parameters even after short-term therapy.Limitations of the present study, including the small number of cases, they said, suggest that additional research is needed to define the nature and magnitude of the diabetes risk associated with second-generation antipsychotic use among children.The study received funding from the Agency for Healthcare Research and Quality.An abstract of “Antipsychotic Medication Use Among Children and Risk of Diabetes Mellitus” is posted at http://pediatrics.aappublications.org/content/128/6/1135. ISSUES NewArchived

Antipsychotic Medication Use Among Children and Risk of Diabetes Mellitus

To assess whether the risk of incident diabetes was increased with the use of second-generation antipsychotics (SGAs) in a large diverse cohort of children. A retrospective study was conducted by using the administrative databases of 3 health plans participating in the Health Maintenance Organization Research Network. Children 5 to 18 years of age who initiated SGA therapy between January 2001 and December 2008 and 2 comparison groups, namely, nonusers of psychotropic drugs and users of antidepressant medications, were identified. Diagnoses from inpatient and outpatient records, pharmacy dispensings, and outpatient laboratory results were used to identify incident cases of diabetes. The crude incidence rate of diabetes for the SGA-exposed cohort was 3.23 cases per 1000 person-years (95% confidence interval [CI]: 1.67-5.65), compared with 0.76 cases per 1000 person-years (95% CI: 0.49-1.12) among nonusers of psychotropic medications and 1.86 cases per 1000 person-years (95% CI: 1.12-2.90) among antidepressant users. The risk of incident diabetes was significantly increased among SGA users (unadjusted incidence rate ratio: 4.24 [95% CI: 1.95-8.72]) in comparison with nonusers of psychotropic medications but was not significantly increased in comparison with antidepressant medication users (unadjusted incidence rate ratio: 1.74 [95% CI: 0.77-3.78]). Although we found a potentially fourfold increased rate of diabetes among children exposed to SGAs, the findings were inconsistent and depended on the comparison group and the outcome definition.

A real-world data analysis of dose effect of second-generation antipsychotic therapy on hemoglobin A1C level

Previous studies have demonstrated an association between certain second-generation antipsychotics (SGAs) and diabetes mellitus. The study assessed the impact of SGA dose on hemoglobin A1C (HbA(1c) >6.0) levels in a real-world setting. Patients aged ≥ 18 years during 2002-2006 in Ingenix LabRx claims database were included. The database collects medical and prescription claims and a subset of laboratory results for an employed, commercially insured population distributed throughout the United States. Patients with previously diagnosed diabetes, identified by the ICD-9-CM code of 250.x or use of antidiabetic agents, were excluded. The main exposure measure was the cumulative dose over a 30 day period before the HbA(1c) test, calculated as [sum of (number of pills per day×strength)]/100. A logistic regression was used to examine the relation with HbA(1c) >6.0 by tertile of the cumulative dose and average daily dose, adjusted for the covariates. The study included 391 patients on olanzapine, 467 on quetiapine, and 262 on risperidone. Patients treated with aripiprazole or ziprasidone (n=212) were included as a secondary reference because of their minimal metabolic risk. Compared to lower (Tertiles 1 and 2) cumulative doses of risperidone, patients with a high cumulative dose of risperidone (Tertile 3) had a significantly higher odds ratio (OR) for HbA(1c) >6.0 (adjusted OR=2.45; 95% confidence interval=1.13-5.32; P=0.023). A similar increase in OR was seen in patients with high cumulative dose of olanzapine (2.41; 1.19-4.89; P=0.015). Analyses of average daily dose revealed that quetiapine ≥ 400 mg/day and risperidone ≥ 2 mg/day had an OR of 2.29 (1.04-5.06; P=0.041) and 2.28 (1.08-4.83; P=0.032), respectively, compared to aripiprazole/ziprasidone. Both olanzapine groups (≥ 10 and <10mg/day) were associated with a significantly increased OR. All results remained similar after further adjustment for the predicated probability of having an HbA(1c) test and additional medication covariates. In this claims data study, use of olanzapine was associated with elevated HbA(1c) and risperidone and quetiapine appeared to have dose-related association with elevated HbA(1c). One of the limitations of a claims data analysis is the lack of information on potential confounders such as ethnicity and weight.

Second-generation antipsychotics in major depressive disorder: update and clinical perspective.

The aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD). In MDD, SGA monotherapy or adjunctive therapy to conventional antidepressants showed rapid onset of antidepressant efficacy. Although maintenance data are limited, quetiapine monotherapy, risperidone adjunctive therapy, and amisulpride adjunctive therapy significantly delayed the time to relapse as compared with placebo. In general, extrapyramidal symptoms appeared to be low with SGAs, but a higher incidence of akathisia was observed with aripiprazole. An elevated risk of weight gain was observed with olanzapine-fluoxetine combination, risperidone, aripiprazole, and quetiapine compared with placebo. At present, there are insufficient data to confidently distinguish between different SGAs in the treatment of MDD. A recent meta-analysis found that adjunctive SGAs were significantly more effective than placebo, but differences in efficacy were not identified among the studied agents, nor were outcomes affected by trial duration or the method of establishing treatment resistance. Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression. Clinicians should routinely monitor for cardiometabolic side-effects and extrapyramidal symptoms during SGA therapy.

Quality of monitoring for metabolic effects associated with second generation antipsychotics in patients with schizophrenia on public insurance

Second generation antipsychotics (SGA) are associated with new onset diabetes, dyslipidemia and significant weight gain. Patients with schizophrenia are also at an increase risk of developing metabolic disorders, making routine metabolic monitoring important in patients with schizophrenia. The objective of our study was to identify glucose and lipid monitoring rates in Kansas Medicaid beneficiaries with schizophrenia who received long-term SGA therapy both before and after metabolic concerns of SGA had been introduced in the medical literature and after publication of metabolic monitoring guidelines from professional organizations in 2004. A retrospective cohort study was conducted using health care claims of Kansas Medicaid enrollees (age 18–64 years) with a diagnosis of schizophrenia and receiving long-term SGA. Proportions of these patients receiving annual blood glucose and serum lipid laboratory tests were calculated for two periods:2002–2003 and 2005–2007. Bivariate and multivariate analyses were conducted to determine associations between demographic characteristics and monitoring outcomes. Among 2204 persons in the 2002 cohort, 23% received annual blood glucose monitoring and 10.1% received lipid monitoring. Among 1646 persons in the 2006 cohort, 75.3% received blood glucose monitoring and 52.5% received lipid monitoring. Our findings showed significant increases in blood glucose and lipid monitoring rates observed across a 4-year period in Kansas Medicaid enrollees with schizophrenia receiving SGA. The large rise in monitoring over time may be due to increase awareness of metabolic concerns by mental health care specialists, whom patients with schizophrenia are likely to receive their care from.