Second-generation Antipsychotic Prescribing Research Articles

Patterns of drug prescribing in inpatients withfirst episode of schizophrenia spectrum disorder: The role of guidelines .

The great discrepancy between clinical guidelines and the routine psychiatric practice in the treatment of schizophrenia is a subject of intensive research, with the aim to promote the rational prescribing of antipsychotics. The aim of this study was to analyze the pattern of drug prescribing in the treatment of inpatients with the first episode of schizophrenia spectrum disorders and the impact of the implementation of the Serbian National Guideline for the Diagnosis and Treatment of Schizophrenia. This cross-sectional study was conducted at the Clinic for Mental Disorders "Dr Laza Lazarević" in Belgrade and included a consecutive sample of 675 previously drug-naïve patients with the first episode of schizophrenia spectrum disorders. The data were obtained from the patients' medical records. The analysis of therapy prescribed at discharge included antipsychotics and non-antipsychotic adjuvant therapy. Descriptive statistical methods and methods for testing statistical hypotheses were used to analyze the primary data. The prescribing of second-generation antipsychotics has increased both within antipsychotic monotherapy and within antipsychotic polypharmacy during the period of the study. The use of adjuvant non-antipsychotic pharmacotherapy was very common, but use of benzodiazepines, carbamazepine, and anticholinergic drugs significantly decreased. Long-acting forms of antipsychotics have been rarely used (9.3%). Clozapine was in general underprescribed (10.4%). The National Guideline for the Diagnosis and Treatment of Schizophrenia most likely contributed to some positive changes in prescribing patterns during the treatment of the first psychotic episode in daily clinical practice in Serbia. However, antipsychotic polypharmacy and irrational use of adjuvant therapy was still prevalent.

Simulated Effects of Policies to Reduce Diabetes Risk Among Adults With Schizophrenia Receiving Antipsychotics.

Second-generation antipsychotics increase the risk of diabetes and other metabolic conditions among individuals with schizophrenia. Although metabolic testing is recommended to reduce this risk, low testing rates have prompted concerns about negative health consequences and downstream medical costs. This study simulated the effect of increasing metabolic testing rates on ten-year prevalence rates of prediabetes and diabetes (diabetes conditions) and their associated health care costs. A microsimulation model (N=21,491 beneficiaries) with a ten-year time horizon was used to quantify the impacts of policies that increased annual testing rates in a Medicaid population with schizophrenia. Data sources included California Medicaid data, National Health and Nutrition Examination Survey data, and the literature. In the model, metabolic testing increased diagnosis of diabetes conditions and diagnosis prompted prescribers to switch patients to lower-risk antipsychotics. Key inputs included observed diagnoses, prescribing rates, annual testing rates, imputed rates of undiagnosed diabetes conditions, and literature-based estimates of policy effectiveness. Compared with 2009 annual testing rates, ten-year outcomes for policies that achieved universal testing reduced exposure to higher-risk antipsychotics by 14%, time to diabetes diagnosis by 57%, and diabetes prevalence by .6%. These policies were associated with higher spending because of testing and earlier treatment. The model showed that policies promoting metabolic testing provided an effective approach to improve the safety of second-generation antipsychotic prescribing in a Medicaid population with schizophrenia; however, the policies led to additional costs at ten years. Simulation studies are a useful source of information on the potential impacts of these policies.

Prescribing trends and indications of antipsychotic medication in Hong Kong from 2004 to 2014: General and vulnerable patient groups.

Antipsychotic-prescribing patterns remain unclear in Asia. The aims of our study were to investigate prescribing trends of antipsychotic medication in the general population, children, and older patients by drug generation (first or second), the prescribing trend in pregnant women, the probable indication for antipsychotic prescription, and the prescribing trend by dosage form. This descriptive study identified and included all patients prescribed with antipsychotic in Hong Kong from 2004 to 2014 using the Clinical Data Analysis and Report System. This study calculated and reported the prevalence of antipsychotic prescribing in patient groups of interest, the percentage with diagnoses of mental disorders were derived, and the prevalence of antipsychotic by dosage forms. The study included 10109206 prescriptions of any antipsychotics to 256903 patients. Over the study period, the prevalence of antipsychotic prescribing increased from 1.06% to 1.54% in the general population, from 0.10% to 0.23% in children (3-17years old), and from 2.61% to 3.26% in older patients (≥65years old). The prevalence of second-generation antipsychotics increased, but the prevalence of first-generation antipsychotics did not. Prevalence of antipsychotic prescribing in prepregnancy, pregnancy, and postpartum timeframes varied from 0.18% to 0.38%. The percentage of incident prescriptions with a diagnosis of psychosis decreased from 54.1% to 47.5%. Antipsychotics have been increasingly prescribed in the general population, children, and older patients. There is an increase in second-generation antipsychotic prescribing. Over half of incident users had a recent diagnosis of a nonpsychotic mental disorder in 2014, suggesting that off-label prescribing of antipsychotics might be common.

Second-Generation Antipsychotic Prescribing Patterns for Pediatric Patients Enrolled in West Virginia Medicaid.

The prescribing of second-generation antipsychotics for young people has increased dramatically. Studies have shown that children enrolled in Medicaid are more likely than those with private insurance to receive antipsychotics, leading many states to require prior authorization (PA) for their use. However, little is known about how PA programs affect prescribing patterns for antipsychotics or other psychotropic medications. This study examined a PA program for second-generation antipsychotic use for children under 18 in West Virginia Medicaid. Prescribing rates for antipsychotics and other psychotropic classes were assessed. Administrative claims from West Virginia Medicaid and the Children's Health Insurance Program for September 2014 to July 2016 were examined (N=273,369 prescriptions) with an interrupted time-series design. Segmented linear regression was used to model both immediate effects and trends in prescribing rates before and after implementation of the PA program in August 2015. After PA program implementation, the prescribing rate for second-generation antipsychotics immediately dropped by 17% from prior levels, adjusted for preexisting trends, and further declined in the following months. Prescribing rates for all second-generation antipsychotics except for aripiprazole decreased significantly. Benzodiazepine prescribing increased in the month after PA program implementation but immediately returned to prepolicy rates, and sustained compensatory prescribing was not observed for any psychotropic drug class. Implementation of a second-generation antipsychotic PA program for children under age 18 resulted in a significant decrease in the prescribing rate for this class of medication, without sustained compensatory prescribing of other psychotropic classes.

Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia.

To determine whether elderly veterans with posttraumatic stress disorder (PTSD) and dementia are more likely to be prescribed second-generation antipsychotics (SGAs) than those with PTSD alone. National serial cross-sectional study. Veterans Health Affairs inpatient and outpatient settings. Veterans aged 65 and older with PTSD (excluding schizophrenia or bipolar disorder) with or without concomitant dementia who received care from the Veterans Health Administration between 2003 and 2010 were identified using International Classification of Diseases, Ninth Revision, codes (N = 93,068; 11.1% with dementia). Trends in SGA prescribing and odds of being prescribed an SGA were determined using a multivariable logistic regression model adjusted for clinical, sociodemographic, and geographic covariates. Between 2004 and 2009, SGA prescribing declined annually from 7.0% to 5.1% of elderly veterans with PTSD without dementia and 13.2% to 8.9% in those with dementia; findings over time consistently indicated that veterans with PTSD and dementia had at least twice the odds of being prescribed an SGA as those without PTSD (odds ratios 2.03 (95% confidence interval (CI) = 1.82-2.26) to 2.33 (95% CI = 2.10-2.58). Although the prescribing of SGAs to elderly veterans with PTSD has decreased, prescribing an SGA to those with dementia remained consistently higher than for those with PTSD alone and is problematic given the high prevalence of medical comorbidities in this aging population coupled with the lack of compelling evidence for effectiveness of SGAs in individuals with dementia.

Meta-analysis of population-based studies comparing risk of cerebrovascular accident associated with first- and second-generation antipsychotic prescribing in dementia.

Second-generation antipsychotics (SGAs) are often prescribed in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), however, their use has been discouraged in light of clinical trials suggesting that they cause an increased risk of cerebrovascular accidents (CVAs). Aim of the study was to assess relative risk of CVA in dementia patients prescribed SGA rather than first-generation antipsychotics (FGAs), through meta-analysis of population-based studies. A literature search was conducted using several relevant databases. Five studies were included in the review and data were pooled to conduct meta-analysis using the inverse variance method. A total of 79,910 patients were treated with SGAs and 1287 cases of CVA were reported. Of 48,135 patients treated with FGAs, a total of 511 cases of CVA were reported. The relative risk of CVA was 1.02 (95% CI 0.56-1.84) for the SGA group. There was no significant difference in the risk of stroke (p = 0.96) between groups, but significant heterogeneity was found among the results of included studies (p < 0.001). Meta-analysis of population-based data suggested that the use of SGAs as opposed to FGAs to control BPSD is not associated with significantly increased risk of CVA. Copyright © 2016 John Wiley & Sons, Ltd.

Evolution of First-generation and Second-generation Antipsychotic Prescribing Patterns in Belgium Between 1997 and 2012: A Population-based Study.

In recent decades, a substantial increase in prescriptions of antipsychotics has been reported in several countries. This increase in antipsychotic sales has been attributed to the success of second-generation antipsychotics. This national register-based study investigated the evolution of outpatient antipsychotic sales in Belgium between 1997 and 2012. The impact of the specialization of the prescriber and the demographic characteristics of both prescribing doctors and patients were examined. The study used data obtained from the Belgian National Institute for Health and Disability Insurance and IMS Health Belgium. Over this 15-year period, antipsychotic sales increased by 122% in Belgium. This growth was mainly explained by a 3-fold increase in antipsychotic prescriptions by psychiatrists and neurologists. Overall, only 29.5% of prescriptions for antipsychotics were for psychotic disorders and only 26.2% of prescriptions for antipsychotics were for mood disorders, suggesting a large amount of off-label use. A significant shift toward second-generation agents was found in prescriptions by both psychiatrists and general practitioners, although there may have been a small delay in moving toward second-generation agents in the latter group. This increase in second-generation antipsychotic prescribing was mainly due to the steep rise in sales of quetiapine, followed by olanzapine and risperidone. The shift toward the newer products was also mainly seen in younger prescribers. The results of this study suggest that there has been an increase in adequate management of patients in need of antipsychotic treatment. Nevertheless, very few of the patients received continued treatment throughout the year, which implies that few outpatients with schizophrenia are receiving adequate treatment.

Incidence of Cardiovascular Outcomes and Diabetes Mellitus Among Users of Second-Generation Antipsychotics

To examine the risk of cardiovascular outcomes and diabetes mellitus in patients prescribed second-generation antipsychotics. From the MarketScan claims database, nondiabetic adults prescribed aripiprazole between July 2003 and March 2010 were propensity score-matched with patients prescribed olanzapine, quetiapine, risperidone, and ziprasidone. Patients were followed through the claims for International Classification of Diseases, Ninth Revision codes indicating myocardial infarction, stroke, heart failure, coronary bypass/angioplasty procedures, and incident diabetes. Incidence rates of each outcome were calculated and compared between aripiprazole and the other second-generation antipsychotics using Cox models. Aripiprazole initiators were matched 1:1 to 9,917 olanzapine, 14,935 quetiapine, 10,192 risperidone, and 5,696 ziprasidone initiators. Increased risk was found with olanzapine for stroke (hazard ratio = 1.43; 95% confidence interval, 1.05-1.95) and any cardiovascular event (1.28; 1.05-1.55); with quetiapine for stroke (1.58; 1.19-2.09), heart failure (1.55; 1.15-2.11), and any cardiovascular event (1.50; 1.25-1.79); and with risperidone for stroke (1.54; 1.12-2.12), heart failure (1.43; 1.02-1.99), and any cardiovascular event (1.49; 1.21-1.83). Ziprasidone showed no significant difference in risk from aripiprazole for any outcome. Incidence of diabetes ranged from 18 to 21 events per 1,000 person-years in each cohort and did not differ significantly between second-generation drugs. This analysis of real-world data found lower risk of some cardiovascular events with aripiprazole than with olanzapine, quetiapine, or risperidone, but no differences were found with ziprasidone. There were no significant differences in risk of diabetes. Limitations include use of claims data and inability to adequately control for differential prescribing of second-generation antipsychotics to patients at higher risk of diabetes.

Cognitive-Behavioral Therapy as an Adjunct to Second-Generation Antipsychotics in the Treatment of Schizophrenia

This study determined whether adding cognitive-behavioral therapy to treatment for outpatients with schizophrenia would be more effective than the use of second-generation antipsychotics alone. Thirty-three patients were randomly assigned to receive either second-generation antipsychotics alone (N=18) or second-generation antipsychotics plus cognitive-behavioral therapy (N=15). All patients received pharmacotherapy from a single provider and in a predetermined standard manner. Psychopathology ratings were done at baseline, at the end of treatment (12 weeks) and three months after completion of treatment (24 weeks). Twenty-five (76%) patients completed baseline and 12-week evaluations, and 17 (68%) patients who finished treatment also completed evaluations at 24 weeks. At the end of treatment persons in the second-generation antipsychotics plus cognitive-behavioral therapy group were rated as having less severe delusions than patients in the group receiving second-generation antipsychotics only, and this difference was maintained three months after treatment ended. Adding cognitive-behavioral therapy may help with reducing the severity of delusions among patients with schizophrenia.

Off-Label Use of Second-Generation Antipsychotic Agents Among Elderly Nursing Home Residents

This study examined off-label and evidence-based use of second-generation antipsychotic agents among elderly nursing home residents and factors associated with off-label use. This study involved a retrospective, cross-sectional analysis of data from the 2004 National Nursing Home Survey (NNHS). The sample included nursing home residents 65 years and older who received second-generation antipsychotic agents. This study used an indication-based definition of off-label use established by the U.S. Food and Drug Administration (FDA). Evidence-based use included FDA-approved indications and indications for which the Agency of Healthcare Research and Quality found at least moderate strength of evidence of effectiveness. Descriptive statistics were used to examine the prevalence of off-label and evidence-based use. Multiple logistic regression was used to examine the patient and facility factors associated with off-label use of second-generation antipsychotics. According to the 2004 NNHS, 308,990 (23.5%) elderly nursing home residents received at least one second-generation antipsychotic agent. Of those using second-generation antipsychotics, 86.3% received them for off-label indications and 56.9% received them for an evidence-based use. Multivariate analysis found that age (> or =75 years), self-pay for nursing home care, diagnosis of dementia, and residing in a nonprofit nursing home were positively associated with off-label use, whereas receiving Medicaid benefits was negatively associated with such use. Although second-generation antipsychotics were frequently used for off-label indications, most of the usage was evidence based among elderly nursing home residents. However, the high level of non-evidence-based use combined with recent safety and efficacy data suggests an urgent need to address the evidence base for this vulnerable population.

Metabolic Testing Rates in 3 State Medicaid Programs After FDA Warnings and ADA/APA Recommendations for Second-Generation Antipsychotic Drugs

In 2003, the Food and Drug Administration (FDA) required a warning on diabetes risk for second-generation antipsychotic (SGA) drugs. The American Diabetes Association (ADA) and American Psychiatric Association (APA) recommended glucose and lipid testing for all patients starting to receive SGA drugs. To characterize associations between the combined warnings and recommendations and baseline metabolic testing and SGA drug selection. Interrupted time-series analysis. California, Missouri, and Oregon. Patients A total of 109 451 individuals receiving Medicaid who began taking SGA medication and a control cohort of 203 527 patients who began taking albuterol but did not receive antipsychotic medication. Prewarning and postwarning trends in metabolic testing were compared using laboratory claims for the cohort collected January 1, 2002, through December 31, 2005. Changes in SGA prescribing practices were similarly evaluated. Monthly rates of baseline serum glucose and lipid testing for SGA-treated and propensity-matched albuterol-treated patients and monthly share of new prescriptions for each SGA drug. Initial testing rates for SGA-treated patients were low (glucose, 27%; lipids, 10%). The warning was not associated with an increase in glucose testing among SGA-treated patients and was associated with only a marginal increase in lipid testing rates (1.7%; P = .02). Testing rates and trends in SGA-treated patients were not different from background rates observed in the albuterol control group. New prescriptions of olanzapine (higher metabolic risk) declined during the warning period (annual share decline, 19.9%; P < .001). New prescriptions of aripiprazole (lower metabolic risk) increased during the warning period (share increase, 12.1%; P < .001) but may be attributable to the elimination of prior authorization in California during the same time frame. Quetiapine, risperidone, and ziprasidone use were not associated with the warning. In a Medicaid-receiving population, baseline glucose and lipid testing for SGA-treated patients was infrequent and showed little change following the diabetes warning and monitoring recommendations. A change in SGA drug selection consistent with intentions to reduce metabolic risk was observed.

Metabolic Risk Status and Second-Generation Antipsychotic Drug Selection

Routine metabolic screening and consideration of patient metabolic status in the choice of a second-generation antipsychotic (SGA) medication are recommended. This study evaluated the association between abnormal blood glucose and lipid values and SGA prescribing patterns. A retrospective cohort study using administrative data from 2 managed care plans in the United States evaluated 7904 adults initiating SGA therapy between 2001 and 2004. Baseline serum glucose, total cholesterol, and triglyceride values were available for 989 patients (12.5%), and follow-up assessments were done in 699 patients (8.8%). Abnormal values were defined as the following: total cholesterol, 200 mg/dL or higher; triglycerides, 200 mg/dL or higher; and glucose, 126 mg/dL or higher. The likelihood of abnormal laboratory values being associated with selection of a lower metabolic risk SGA drug (aripiprazole or ziprasidone) and with switching decisions was assessed using multivariate logistic regression models. Thirteen percent of the patients had glucose and lipid tests within 6 months of starting SGA therapy. The likelihood of starting a patient on an SGA drug with lower metabolic risk (ziprasidone: odds ratio, 3.26; 95% confidence interval, 1.25-8.47; aripiprazole: odds ratio, 2.13; 95% confidence interval, 0.77-5.88) was higher if the patient had elevated glucose values but was not associated with elevated cholesterol or triglyceride values or if the patient had preexisting diabetes or dyslipidemia. Abnormal glucose and lipid values were not associated with switching SGA medications in the first 6 months of therapy. Among patients who did switch SGA medications, elevated glucose and lipid values were not associated with a greater likelihood of switching to aripiprazole or ziprasidone. Low rates of recommended monitoring were observed. Abnormal metabolic parameters among those who were tested were not consistently associated with the selection of an SGA drug with lower metabolic risk.

Second-generation antipsychotic prescribing on the increase

Second-generation antipsychotic prescribing on the increase

Antipsychotic Polypharmacy Trends Among Medi-Cal Beneficiaries With Schizophrenia in San Diego County, 1999-2004

Antipsychotic Polypharmacy Trends Among Medi-Cal Beneficiaries With Schizophrenia in San Diego County, 1999-2004

Although the prescribing of second-generation antipsychotics is becoming popular in Japan, prescription rates for first-generation antipsychotics remain high,

Although the prescribing of second-generation antipsychotics is becoming popular in Japan, prescription rates for first-generation antipsychotics remain high,

Overdoses and Ingestions of Second-Generation Antipsychotics in Children and Adolescents

We reviewed the available published data on intentional or unintentional secondgeneration antipsychotic overdoses in children and adolescents. The prescribing of secondgeneration antipsychotics has continued to increase over the past decade for children, adolescents, and adults. The authors reviewed the existing literature to determine the circumstances, presenting problems, treatment, and outcomes of youths who were exposed to nontherapeutic doses of these medications. A systematic English-language Medline search of all reports (1989-2005) and a review of the bibliographies of all articles obtained was done to identify papers reporting an overdose or ingestion of a second-generation antipsychotic. Data were reviewed on clozapine, risperidone, olanzapine, ziprasidone, quetiapine, and aripiprazole. The annual reports of the American Association of Poison Control Centers National Data Collection System were reviewed from 1990 to 2003, the most recent report currently available. All fatalities in children and youths under 18 years of age were included. The literature review identified 40 reports that included 63 patients, ranging in age from 1 day to 17 years of age. The clinical presentations included drowsiness, lethargy, agitation, irritability, combativeness, and tachycardia. There were 11 fatalities in the cases reviewed, 1 from clozapine overdose, 3 from risperidone overdose, 2 from olanzapine overdose, and 5 from quetiapine overdose. All other cases reported no significant sequelae and resolved without any reported clinical consequences. Duration of overdose symptoms ranged from 24 hours to 7 days. One case of clozapine intoxication showed resolution of symptoms in 6 hours and, in another case of olanzapine overdose, symptoms resolved in 13 days. The most frequently employed treatments included intubation, gastric lavage, activated charcoal, intravenous fluids, artificial respiration, and restraints or sedatives. There is a need for future case reports to include serum medication level, weight of patient, coingestants, the health of the patient at baseline, relevant laboratory and toxicology studies and a standardized scale to rate the level of consciousness, such as the Glasgow Coma Scale. The existing pharmacovigilance data reports indicate these medications are relatively safe when taken in overdose, particularly when coingestants are not involved.