Indiana Medicaid Drug Utilization Review Board Newsletter

Transcription

1 Indiana Medicaid Drug Utilization Review Board Newsletter Volume 15 Issue 1 April 2012 Indiana Medicaid DUR Board Room W382 Indiana State Government Center, South 402 West Washington Street Indianapolis, Indiana DUR Board Members Philip N. Eskew, Jr., MD, Chair Carol Ott, PharmD, BCPP, Vice Chair William J. Brown, MS, RPh Medhane Cumbay, Ph.D Petra Fippen, RPh Rhea Ellen Miller-Boley, RPh Brian Musial, RPh Thomas R. Marshall, MD Nancy Swignonski, MD Patricia A. Treadwell, MD John J. Wernert, MD Inside this Issue Atypical Antipsychotic Use in Children & Adolescents Atypical Antipsychotic Use in Children and Adolescents Introduction: Since their introduction into the United States market, atypical antipsychotics have received wide acceptance and use over the older, typical antipsychotics (e.g. chlorpromazine, haloperidol). One reason is the atypical antipsychotics, in general, produce fewer movement-related adverse effects (extrapyramidal symptoms) than older antipsychotics. In addition, they were believed to demonstrate superior efficacy, especially against negative symptoms of schizophrenia. 1 While advantages in terms of extrapyramidal symptoms continue to be demonstrated, the purported advantages in effectiveness have been questioned. 2 Superiority in terms of cognitive effects do appear to be valid with the atypical antipsychotics. 3 However, the advantages in terms of extrapyramidal symptom-related adverse effects have been tempered by concerns about metabolic adverse effects (i.e. weight gain, lipid abnormalities, glucose regulation, etc.). 4 These metabolic effects raise questions about the long-term tolerability of atypical antipsychotics. This article will provide a general review of the available atypical antipsychotics and then review data related to their use in children and adolescents. Available Atypical Antipsychotics: The first atypical antipsychotic to become available was clozapine (Clozaril ). Due to clozapine s (Clozaril ) potential toxicity, it s generally reserved for treatment-resistant patients. The first atypical antipsychotic to be used as a first-line agent was risperidone (Risperdal ). It is considered to be the most typical of the atypical agents. In a dose-related manner, risperidone is associated with extrapyramidal symptoms that are more commonly observed with the older typical agents. Olanzapine (Zyprexa ) was the next agent to enter the market and gained acceptance for its lowered incidences of extrapyramidal symptoms within its approved dose ranges. Olanzapine (Zyprexa ) however, has been associated with a higher risk of metabolic adverse events compared to the other atypical antipsychotics 4. Subsequent atypical antipsychotic agents have been developed and marketed with varying clinical profiles. Of the first-line atypical antipsychotics, risperidone became available generically in 2008 and as of April 2012, ziprasidone, olanzapine, and quetiapine immediate-release are expected to have generic equivalent forms introduced. Table 1 shows the available atypical antipsychotics and their Food and Drug (FDA) approved indications in the United States. Continued on page 2

2 VOLUME 15 ISSUE 1 PAGE 2 Available Agents Table 1: FDA Approved Indications for Atypical Antipsychotics * Schizophrenia Mania Bipolar Depression Indications (Age in years) Bipolar Maintenance MDD (adjunctive) Irritability in Autism Abilify (aripiprazole) Clozaril (Clozaril) Fanapt (iloperidone) Geodon (ziprasidone) Invega (paliperidone) Latuda (lurasidone) Risperdal (risperidone) Saphris (asenapine) Seroquel /XR (quetiapine) Zyprexa (olanzapine) (Symbyax # ) (Symbyax # ) * Official prescribing information available by drug at: # Symbyax is a combination of fluoxetine and olanzapine Continued on Page 3

3 VOLUME 15 ISSUE 1 PAGE 3 All available antipsychotics block dopamine activity at the D 2 receptor. 1 This activity is thought to mediate antipsychotic effects but is the source of movement-related adverse effects. Atypical antipsychotics differ from typical agents pharmacologically by being more potent serotonin 5HT 2 receptor blockers than dopamine receptor blockers. 1 The serotonin 5HT 2 activity of the atypical antipsychotics modulate their adverse effects, especially extrapyramidal symptoms, and probably contribute to their efficacy. As a class, atypical antipsychotics share some basic pharmacology, but the individual agents all have unique clinical profiles as well as different FDA approved indications as shown in Table 1. Trends in Atypical Antipsychotic Prescribing in Children: While there are limited FDA approved indications for atypical antipsychotics in children and adolescents (see Table 1), the increasing use of these agents in this population has been well documented. 5-7 In fact, the issue of widespread use of atypical antipsychotics in youth has become the focus of increased concern and controversy. 8,9 At a November 2008 meeting, the Pediatric Advisory Committee to the FDA voted unanimously to recommend gathering more information about on-label and off-label use of the atypical antipsychotic class of drugs in youth with specific attention to age, indication for use, and adverse effects in pediatric patients. 10 In the United States, the number of non-institutionalized children and adolescents being treated with antipsychotic medications from 1987 to 1996 remained relatively constant at less than 300 per 100, However, recent trends in atypical antipsychotic utilization demonstrate greater use of these agents. A study published in 2006 found the number of office-based visits by youth under the age of 21 years, leading to treatment with antipsychotics grew from approximately 275 per 100,000 in 1993 to 1,438 per 100,000 in 2002 (see Figure 1). 6 The absolute number of office visits that led to antipsychotic treatment increased from approximately 201,000 in 1993 to 1,224,000 in Visits per 100,000 Population Figure 1: National trends in office-based visits by children and adolescents that included antipsychotic treatment, Annualized visit rates per 100,000 population were calculated using National Ambulatory Medical Care Survey and US Census Bureau data. 6 Continued on Page 4

4 VOLUME 15 ISSUE 1 PAGE 4 In 2002, atypical antipsychotics were prescribed in 92.3% of the physician office visits that resulted in antipsychotic treatment. Of note, it was found that office visits to psychiatrists resulted in antipsychotic treatment being prescribed 18% of the time while mental health related visits in general resulted in antipsychotic treatment being prescribed 9% of the time. This analysis also found that antipsychotic treatment was significantly more likely for males compared to females, even when controlling for diagnosis. It was also noted that the majority of the antipsychotic treatment in youth occurred among those publicly rather than privately insured. 6 A second study involving antipsychotic use in children and adolescents, reported that antipsychotic agents were prescribed in 5,762,193 outpatient visits between 1995 to Mental health providers were responsible for prescribing over 67% of the antipsychotic prescriptions, although the frequencies of antipsychotic prescriptions increased for both mental health and non-mental health providers during the study period. 7 The number of prescriptions increased from 493,510 in to 2,490,720 in The number of eligible U.S. children included in the study increased from 61,249,041 to 63,270,000. The mean age of children receiving such treatment was 12.9 years old and two-thirds of them were male. Indications for Atypical Antipsychotics in Children: While little is known about the clinical characteristics of the children who were prescribed atypical antipsychotic therapies, there is concern that atypical antipsychotics are being used more frequently for aggression and other behavioral disturbances rather than to treat psychosis, which is the most studied indication for their use. In the Olfson study, the majority of the office visits resulting in antipsychotic treatment were for a disruptive behavior disorder, mood disorder, or other mental disorder; only 14% were for a psychotic disorder. 6 The Cooper study showed the most common diagnosis associated with antipsychotic prescribing was attentiondeficit/hyperactivity disorder (ADHD) or conduct disorder (29%). 7 ADHD is not a well-established indication for antipsychotic medications and is one of the medical conditions singled out by committee members during the November Pediatric Advisory Committee meeting. 10,11 The next most common diagnosis associated with antipsychotic prescribing in the Cooper study was mood disorder, which accounted for 23.6% of antipsychotic use. 7 A non-psychiatric diagnosis resulted in almost 14% of the antipsychotic use in this study, while anxiety or other psychiatric conditions accounted for almost 8% of the use. Schizophrenia (13.5%), autism/other pervasive developmental disorders (7.5%), and Tourette s syndrome (5%), all well established uses of antipsychotic agents, accounted for 26% of all antipsychotic use. Continued on Page 5

5 VOLUME 15 ISSUE 1 PAGE 5 Concerns about Atypical Antipsychotic Use in Children: The limited empiric data related to the use of atypical antipsychotics in youth makes it difficult to assess the riskbenefit ratio of atypical antipsychotic drug therapy in children. While movement-related adverse effects in youth appear to be less common with atypical antipsychotics than with typical antipsychotics, a major concern with the use of atypical antipsychotics is the risk for adverse metabolic effects. 4 Unfortunately, growing evidence suggests the risk for metabolic problems may be more severe in children and adolescents Data provided by one pharmaceutical manufacturer was more specific in addressing this concern. 15 In their assessment of the overall adolescent database, weight gain was the most common adverse effect, occurring in 31.7% of the exposed population. In addition, adolescents gained statistically significant more weight (7.4 kg vs. 3.2 kg, p < 0.001) in short term trials. It was also shown that adolescents experienced statistically significant within-group baseline-to-endpoint changes in fasting glucose (p < 0.001), total cholesterol (p < 0.002), and triglycerides (p < 0.007). Other areas also exist where incidences and concerns of adverse events are potentially different in children and adolescents than in adults. 12 Elevated serum prolactin levels, cardiac concerns, and sedation all appear to be more problematic in youth compared to the adult population. In children and adolescents hyperprolactinemia with atypical antipsychotics appear to be more common than in adults. Hyperprolactinemia may result in gynecomastia, menstrual irregularities, and other effects in both adults and a younger population. These effects can generate more concern in a younger population because the effect of hypogonadism-induced osteoporosis may have more severe consequences. The potential cardiac effects of atypical antipsychotics in children and adolescents remains inconclusive. All of the atypical antipsychotics have some activity that results in prolongation of the QT interval and may result in cardiac dysrhythmias. How different this risk is in the young compared to adults, where most of the available data is, remains unknown. These and other areas of potential risk must all be further investigated as called for by the FDA advisory committee. In 2007, during an Agency for Healthcare Research and Quality (AHRQ) supported Medicaid Medical Directors Learning Network meeting, a plan was developed for a collaborative project to examine the use of atypical antipsychotics for children and adolescents in Medicaid. Indiana Medicaid participated in this study that explored rates and trends of atypical antipsychotic use in children and adolescents in fee-for-service Medicaid. As a follow-up to this study, Indiana Medicaid s upcoming Retrospective DUR educational mailing will re-examine the following issues of the original study in the Indiana Medicaid population: Use of atypical antipsychotics in children 5 years of age or younger Use of higher than recommended doses Use of multiple atypical antipsychotics Use of multiple psychotropic agents. Continued on Page 6

6 VOLUME 15 ISSUE 1 PAGE 6 Conclusion: In recent years, atypical antipsychotics have become common in the office-based mental health treatment of young people. Some atypical antipsychotics have received FDA approval for use in children for selected indications. However, results of recently published clinical trials provide limited support for the short-term safety and efficacy of some atypical antipsychotics for additional indications. There remains an apparent disconnect between community prescribing patterns and the available empiric data related to atypical antipsychotic use in children and adolescents. The AHRQ and Indiana Medicaid claims further demonstrates that atypical antipsychotics are being used to treat a variety of disorders, many of which require more controlled research before such use can be regarded as both safe and effective. There is a pressing need for this research, especially as related to potential long-term consequences of the widespread use of these potent medications in a young population. References: 1. Worrel JA, Marken PA, Beckman SE, Ruehter VL. Atypical antipsychotic agents: a critical review. Am J Health Syst Pharm. 2000; 57: Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Eng J Med. 2005; 353: Keefe RS, Sweeney JA, Gu H, et al. Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52 week comparison. Am J Psychiatry. 2007; 164: American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologist, and North American Association for the Study of Obesity. Consensus Statement on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care, 2004; 27: Olfson M, Marcus SC, Weissman MM, Jensen PS. National trends in the use of psychotropic medications by children. J Am Acad Child Adolesc Psychiatry. 2002; 41: Olfson M, Blanco C, Liu L, et al. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry. 2006; 63: Cooper WO, Arbogast PG, Ding H, et al. Trends in prescribing of antipsychotic medications for US children. Amb Pediatrics. 2006; 6: Janicak PG, Kowatch RA. Are antipsychotics overprescribed for children? Current Psychiatry. 2006; 5: Carey B. Use of antipsychotics by the young rose fivefold. New York Times, June 6, Available at: [last accessed 4/6/12]. 10. United States Food and Drug Administration, Pediatric Advisory Committee. November 18, 2008 meeting. Minutes available at: [last accessed 4/6/12]. 11. Harris, G. Use of antipsychotics in children is criticized. New York Times, November 19, Available at: [last accessed 4/6/12]. 12. Toren P, Ratner S, Laor N, Weeizman A. Benefit-risk assessment of atypical antipsychotics in the treatment of schizophrenia and comorbid disorders in children and adolescents. Drug Saf. 2004; 27: McIntyre RS, Jerrell JM. Metabolic and cardiovascular adverse events associated with antipsychotic treatment in children and adolescents. Arch Pediatr Adolesc Med. 2008;162: Pramyothin P, Khoadhiar L. Metabolic syndrome with the atypical antipsychotics. Curr Opin Endocrinol Diabetes Obes. 2010; Kryzhanovskava LA, Robertson-Plouch CK, Xu W, et al. The safety of olanzapine in aldolescents with schizophrenia or bipolar I disorder: a pooled analysis of 4 clinical trials. J Clin Psychiatry. 2009; 70:

7 VOLUME 15 ISSUE 1 PAGE 7 THE VALUE OF GENERICS Page 7 Top 25 Drugs For Fourth Quarter 2011 Top 25 Drugs 4th Quarter 2011 Ranked by Expenditure Drug Total Claims Total Paid SYNAGIS 100 MG/1 ML VIAL 1,673 $4,423,362 ABILIFY 5 MG TABLET 6,725 $2,844,357 NOVOSEVEN RT 5,000 MCG VIAL 13 $2,370,643 CYMBALTA 60 MG CAPSULE 11,947 $2,284,478 ABILIFY 10 MG TABLET 4,880 $2,193,519 ADVATE 1,801-2,400 UNITS VIAL 54 $2,015,865 ADVAIR DISKUS 9,045 $1,937,215 METHYLPHENIDATE ER 36 MG TABLET 10,578 $1,921,359 LANTUS 100 UNITS/ML VIAL 8,911 $1,747,114 SINGULAIR 10 MG TABLET 10,902 $1,667,219 INCIVEK 375 MG TABLET 96 $1,586,202 PROAIR HFA 90 MCG INHALER 35,277 $1,554,832 SINGULAIR 5 MG CHEWABLE TABLET 10,701 $1,539,233 ABILIFY 20 MG TABLET 2,283 $1,511,578 SEROQUEL 300 MG TABLET 2,771 $1,509,369 ADVATE 2,400-3,600 UNITS VIAL 45 $1,505,210 SPIRIVA 18 MCG CP HANDIHALER 5,755 $1,467,469 VYVANSE 30 MG CAPSULE 9,176 $1,287,363 ABILIFY 15 MG TABLET 2,910 $1,252,953 METHYLPHENIDATE ER 54 MG TABLET 7,655 $1,188,086 LEXAPRO 20 MG TABLET 9,564 $1,179,566 BUDESONIDE 0.5 MG/2 ML SUSPENSION 4,282 $1,174,815 PULMOZYME 1 MG/ML AMPULE 476 $1,127,510 GEODON 80 MG CAPSULE 2,389 $1,116,081 SEROQUEL 400 MG TABLET 1,684 $1,104,392 PDL Listing The Indiana Medicaid PDL listing may be found at the following Web site:

8 VOLUME 15 ISSUE 1 PAGE 8 Top 25 Drugs For Fourth Quarter 2011 Continued Top 25 Drugs 4th Quarter 2011 Ranked by Total Number of Paid Claims Drug Total Claims Total Paid PROAIR HFA 90 MCG INHALER 35,277 $1,554,832 HYDROCODONE/ACETAMINOPHEN MG TABLET 27,428 $67,003 LORATADINE 10 MG TABLET 24,619 $105,083 MAPAP 325 MG TABLET 20,063 $32,511 VENTOLIN HFA 90 MCG INHALER 19,835 $812,371 ALBUTEROL 0.083% SOLUTION 18,542 $200,980 DOK 100 MG CAPSULE 17,919 $35,068 OMEPRAZOLE DR 20 MG CAPSULE 17,301 $113,836 ASPIRIN 81 MG CHEWABLE TABLET 15,340 $21,527 LORATADINE 10 MG TABLET 15,110 $71,687 OYSTER SHELL CALCIUM-VIT D TABLET 14,291 $33,273 HYDROCODONE/ACETAMINOPHEN MG TABLET 13,472 $32,018 SULFAMETHOXAZOLE-TMP DS TABLET 12,428 $32,571 AMOXICILLIN 400 MG/5 ML SUSPENSION 12,426 $96,210 CYMBALTA 60 MG CAPSULE 11,947 $2,284,478 CALCIUM VIT D 400 TABLET 11,283 $25,289 TRAMADOL HCL 50 MG TABLET 10,943 $29,132 SINGULAIR 10 MG TABLET 10,902 $1,667,219 SINGULAIR 5 MG CHEWABLE TABLET 10,701 $1,539,233 METHYLPHENIDATE ER 36 MG TABLET 10,578 $1,921,359 AZITHROMYCIN 250 MG TABLET 10,528 $58,869 CETIRIZINE 10 MG TABLET 10,002 $65,871 AMOXICILLIN 500 MG CAPSULE 9,832 $42,839 HYDROCODONE/ACETAMINOPHEN MG TABLET 9,626 $100,489 FLUTICASONE 50 MCG SPRAY 9,570 $244,668 Program Assistance All prior authorization requests or questions regarding the PDL should be directed to the ACS Clinical Call Center at The articles in this issue of the DUR Newsletter were authored by Doug Brink, PharmD, BCPP, Clinical Pharmacist, ACS The content of this newsletter was approved by the Indiana Medicaid DUR Board