Kelly E. Williams, Pharm.D. PGY2 Psychiatric Pharmacy Resident April 16,2009

Transcription

1 Kelly E. Williams, Pharm.D. PGY2 Psychiatric Pharmacy Resident April 16,2009 List the antipsychotics most often prescribed Compare and contrast the use and adverse effects experienced in the pediatric population Evaluate the appropriateness of multiple antipsychotics for treatment of behavioral disorders Decide how to approach the development of quality of use edits in covered lives < 18 years old 1

2 First Generation /Typical Second Generation/Atypical Haloperidol (Haldol ) Clozapine (Clozaril ) Fluphenazine (Prolixin ) Chlorpromazine (Thorazine ) Pimozide (Orap ) Olanzapine (Zyprexa ) Risperidone (Risperdal )* Quetiapine (Seroquel ) Ziprasidone (Geodon ) Aripiprazole pp (Abilify )* Paliperidone (Invega ) * FDA approved for use in pediatrics Risperidone (Risperdal ) Indications year olds with schizophrenia Dose: 3mg/day year olds with bipolar I disorder Dose: 2.5 mg/day Irritability in 5-16 year olds with autism Dose: 0.5mg/day<20kg or 1mg/day >20kg Aripiprazole (Abilify ) Indications year olds with schizophrenia Dose: 10mg/day year olds with bipolar I disorder Dose:10mg/day 2

3 Safety (risk vs. benefit) Diagnosis i (appropriateness of use) Polypharmacy Expansion of prescribing Childhood Onset Schizophrenia Bipolar I Disorder Irritability associated with autism Agitation/ Aggression Conduct Disorders Pervasive Developmental Disorders Psychosis Affective Disorders Eating Disorders Treatment Resistant Depression +/- psychotic features Anxiety Disorders 3

4 Number of Claims Age, y MDwise Behavioral Health Pharmacy Children s Issues Indiana State Mental Health Quality Advisory Committee 7/17/08 Cost in Millions $7 $6 $5 $4 $3 $2 Antipsychotics ($4.8 million) Antidepressants ($753,000) Psychostimulants/NRI ($6.8 million) $1 $0 Therapeutic Class Of All Claims Antipsychotics = 2.3% Antidepressants= 3.7% Psychostimulants = 8.1% MDwise Behavioral Health Pharmacy Children s Issues I Indiana State Mental Health Quality Advisory Committee 7/17/08 4

5 TRAAY II Aggression/Agitation Childhood Onset Schizophrenia Bipolar Disorder Disruptive Disorders Pervasive Developmental Disorders Adverse Effects Recommendations for the Mental Health Quality Advisory Committee Objective: Develop treatment recommendations for the use of antipsychotics in pediatrics with serious psychiatric disorders and externalized disruptive behaviors Methods: Combination of evidence and consensus-based medicine Results: 14 recommendations were developed to cover treatment phases Evaluation Acute treatment Stabilization Maintenance J Am Acad. Child Adolesc. Psychiatry, 42:2, Feb

6 J Am Acad. Child Adolesc. Psychiatry, 42:2, Feb 2003 Author (n) Age Range, y Drug (avg dose/day,mg) Comments Aman,M et al (118) 5-12 Risperidone (1.16) Double-blind placebo controlled trial included children with sub average intelligence Handen and Harden* (16) Olanzapine (13.7) 8 week, Open-label prospective trial Results Significant improvement with risperidone, long-term use improved symptoms Improvement in hyperactivity and irritability scale, 25% withdrew because of side effects or worsening of symptoms * Industry Sponsored 6

7 Author (n) Age Range, y Drug (avg dose/day,mg) Comments Results Sporn, et al 7-12 Clozapine (425) Both patients t received Both patients t (2) lithium for neutropenia, that resolved +/-symptoms significantly improved Turetz, et al (11) 9-13 Clozapine ( ) Refractory to 2 FGAs and 1 SGA Sikich,et al 8-19 Risperidone (3 + 1) (116) Olanzapine (11 + 5) Molindone ( ) Sporn, et al (54) 6-18 Clozapine ( ) Onset of symptoms before age13 Short & long-term study Significant improvement in +/- symptoms and behavior 8 wk double-blind RCT SGAs did not demonstrate t better Adjunctive BZDs efficacy to molindone given: R 41%, O-20%, M-39% 21/54 were responders at wk 6, at 24 months 68% were still on clozapine Author (n) Kowatch R, et al* (5) Kryzhanovskaya L* (454) Age Range, y Drug (avg dose/day,mg) Comments 6-12 Clozapine ( ) 80% received adjunct lithium and higher doses of clozapine Olanzapine (11.5) A pooled safety analysis of 4 clinical trials 50% (227) had bipolar I disorder Results Better response compared to those with schizophrenia Short duration of treatment High placebo response rate * Industry Sponsored 7

8 Author (n) Age Range, y Drug, (avg dose/day, mg) Comments Results Kroneneberger, W* (24) OROS Methylphenidate (54) AND Quetiapine (330) 10 wk, Open label retrospective controlled trial Large majority (> 80% ) showed improvement in ADHD and aggressive symptoms between weeks 5 and 10 Aman M, et al* (155) 5-12 Risperidone (1) Dextroamphetamine (20) Methylphenidate (35) Pemoline (45) 6 wk, Doubleblind pooled data 4 treatment arms Risp + Stim Stim + PBO Risp + PBO Risp only Significant improvement in irritability, hyperactivity for those in receiving risperidone +/- stimulant use * Industry Sponsored Author (n) RUPP Autism Network* (101) Shea S, et al* (79) Avg Age, y Drug (avg dose/day, mg) Comments 8.8 Risperidone (1.8) 8 wk Double-blind randomized placebo controlled trial + 16 wk maintenance phase 7.5 Risperidone (1.2) 8 wk Double-blind randomized placebo controlled trial 12.1 Quetiapine (250) Retrospective case i St d d l Results Reduction in irritability Risp 57% PBO 14% Reduction in irritability Risp 64% PBO 31% 40% response, 4 wks t t t t Corson A, et al* (20) series. Study med only post treatment Stigler K, et al (25) Valicenti- McDermott, et al* (32) 8.6 Aripiprazole (7.8) 14 wk open label prospective trial 10.9 Aripiprazole (10.6) Retrospective chart review 88% responders 56% responders, 6-15 months post treatment RUPP - Research Units on Pediatric Psychopharmacology * Industry Sponsored 8

9 Authors Correll and Carlson* SGAs Causing Metabolic Syndrome (Weight Gain, Dyslipidemia, Insulin Resistance) High Risk Moderate Risk Low Risk Clozapine, Olanzapine Risperidone, Quetiapine Ziprasidone, Aripiprazole Treatment Options Orlistat, Metformin, or Sibutramine,and frequent monitoring Authors Multiple Antipsychotic Usage Adverse Effects Recommended Treatment Options McIntyre and Jerrell Adverse events similar to adults EPS, TD, and pseudo-parkinsonism Weight gain and other metabolic disorders Digestive and urogenital problems Increased risk of cardiovascular problems Females had a greater risk of developing ADEs Use of multiple antipsychotic medications confers an increased risk of developing ADEs Monotherapy and frequent monitoring * Industry Sponsored Include FDA- approved indications for SGAs Consider ICD-9 Codes for validation of use Restrict t prescribing of antipsychotics to psychiatrists i t Develop a decision tree for the treatment of disruptive behaviors, aggression, depression, psychosis, etc using appropriate dose and duration SSRIs Mood Stabilizers Antipsychotics No less than 2 weeks at a therapeutic dose before considering treatment failure or dose increase Unless unable to tolerate therapeutic dose Assessment of efficacy 9

10 Laboratory values at baseline and every 6-12 months, dependent upon individual parameters HgbA1c, LFTs, Fasting Lipid Panel Consider using recommendations from the American Diabetic Association, American Pediatric Association, and National Cholesterol Education Program, to include in the educational packet At baseline and each subsequent visit assess and document movement disorders, weight/height, BMI percentile, BP, HR and signs of hyperprolactinemia 10