Atypical Antipsychotic Drug Use in Children and Adolescents

1. Atypical Antipsychotic Drug Use in Children and Adolescents By: Alicia Shell Spring 2008 Advisor: Dr. Bill Grimes, PA-C

2. Why is this important to us? • As primary care providers we are going to have the opportunity to act as a psychiatric first responder • Referral to psychologist/psychiatrist • Follow-up care (esp. in rural areas)

3. Background • Atypical Antipsychotic Drugs: A “newer” class of prescription medications used to treat psychiatric conditions • Exact MOA unknown but thought to be due to blockade of both the dopamine-2 receptor as well as the serotonin 5-HT2A receptor

4. Atypical Antipsychotic Drugs • Clozapine (BN: Clozaril) • Risperidone* (Risperdal) • Olanzapine (Zyprexa) • Quetiapine (Seroquel) • Ziprasidone (Geodon) • Aripiprazole (Abilify)

5. Atypical Antipsychotic Drugs cont’d… • Used to treat a wide variety of psychiatric disturbances including: • Schizophrenia • Acute mania • Bipolar mania • Psychotic agitation • Bipolar maintenance

6. Atypical Antipsychotic Drugs cont’d… • Their use has supplanted the older “typical” antipsychotic drugs due to the fact that they are thought to cause less extrapyramidal side effects such as tardive dyskinesia • This has resulted in a substantial increase in the use of antipsychotics for childhood behavioral disorders

7. Atypical Antipsychotic Drugs cont’d… • Dangerous side effects include: weight gain, diabetes, and hyperlipidemia • Few studies have been done to show how these drugs affect children • Possibility that children are more likely to develop these side effects than adults (Fritz 2006)

8. Atypical Antipsychotic Drugs cont’d… • Recent studies have documented a dramatic increase in prescribing rates for all of these medications to children and adolescents ranging from 200% to over 500% (Fritz 2006)

9. They are being prescribed in the pediatric population to treat: • Oppositional defiant disorder (ODD) • Conduct disorder (CD) • Mood disorders (i.e. Bipolar disorder) • Attention deficit/hyperactivity disorder (ADHD) • Childhood-onset schizophrenia

10. Early-onset Bipolar Disorder or Childhood Bipolar Disorder • Historically under-recognized, now occasionally over-diagnosed, mood disorder affecting approximately 1% of all children and adolescents (Faust 2006) • Diagnosing this disorder is particularly difficult because it can present with a broad spectrum of symptoms of varying severity

11. Initial presentation may involve complaints of: • Moodiness • Frequent or aggressive oppositional behaviors • Anger that does not resolve within 15 minutes • Sadness and easy crying • Inattention • Impulsiveness

12. Why is early diagnosis of this disorder important? • Decrease the morbidity and mortality that is associated with it • Currently estimated that 25-50% of all BD patients will make a suicide attempt in their lifetime and approx. 20% will succeed (Faust 2006) • Adolescents with BD are at the greatest risk, particularly those who are rapid cyclers

13. How do we treat it? • Unfortunately, there are no specific medications that are indicated for treating this condition in children • Instead, physicians are using antipsychotic medications designed for adults • The problem with this is that the usual adult treatment may not address the needs of young people with recent-onset psychosis and the psychological therapies for psychosis need to be age-specific (Haddock 2006)

14. Antipsychotic prescribing practices in children and adolescents: • Clinical experience rather than scientific evidence (Pappadopulos 2002) • May be the result of social pressure to use these meds when patient behavior is particularly disruptive or dangerous

15. FIND strategy to identify manic symptoms: • Frequency: symptoms occur most days in a week • Intensity: symptoms are severe enough to cause extreme disturbance in one domain or moderate disturbance in two or more domains • Number: symptoms occur three or four times a day • Duration: symptoms occur 4 or more hours a day, total, not necessarily contiguous (Am. Acad. Child & Adolesc. Psychiatry 2005)

16. If a psychiatric diagnosis is confirmed… • Start with family-focused psychotherapy • Parent management training • Dyadic (parent-child) psychotherapy • If drugs are deemed necessary, suggest that that they be used in conjunction with psychotherapy (Grimes 2007)

17. Before initiating treatment with an atypical antipsychotic: • A personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease • Weight and height so that BMI can be calculated • Measurement of waist circumference • Blood pressure • Fasting plasma glucose • Fasting lipid profile

18. Weight should be reassessed at 4, 8, and 12 weeks after initiating or changing therapy with an atypical antipsychotic and quarterly thereafter at the time of routine visits • If a patient gains more than 5% of his or her initial weight at any time during therapy, the patient should be switched to an alternative agent • Note: These guidelines were not written for a pediatric population and the 5% weight gain threshold may not be sensitive enough for children and adolescents (Kowatch 2005)

19. Conclusions • Be very discriminate in regards to who we give these drugs to • Proper evaluation of child’s condition • Monitor, monitor, monitor! • Don’t get complacent • Be vigilant in regards to lab tests, psychiatric evaluations, weight monitoring, etc.

20. References • ACP Medicine 3rd edition. Volume 2: 208, 211 • Ananth, J., Parameswaran, S., and Gunatilake, S. Side effects of atypical antipsychotic drugs. 2004; Current Pharmaceutical Design 10: 2219-2229. • Cooper, W., Hickson, G. et al. New users of antipsychotic medications among children enrolled in TennCare. 2007; Arch Pediatr Adolesc Med158: 753-759. • Curtis, L., Masselink, L. et al. Prevalence of atypical antipsychotic drug use among commercially insured youths in the United States. 2005; Arch Pediatr Adolesc Med 159: 362-366. • Dunner, DL. Safety and tolerability of emerging pharmacological treatments for bipolar disorder. 2005; Bipolar Disorders 7: 307-325. • Faedda, G., Baldessarini, R. et al. Pediatric bipolar disorder: phenomenology and course of illness. 2004; Bipolar Disorders 6: 305-313. • Faust, D., Walker, D., and Sands, M. Diagnosis and management of childhood bipolar disorder in the primary care setting. 2006; Clinical Pediatrics 45: 801-808. • Fritz, G. First do no harm: prescribing new antipsychotic medications to children. 2006; The Brown Univ Child and Adolescent Behavior Letter 22(10): 8. • Gogtay, N., Sporn, A. et al. Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. 2004; Arch Gen Psychiatry 61: 17-22. • Grimes, J.C. Psychiatric medication treatment guidelines for preschoolers: issued by child mental health experts. 2007; Medical News Today • Haddock, G., Lewis, S. et al. Influence of age on outcome of psychological treatments in first-episode psychosis. British J. of Psychiatry 188: 250-254. • Hermann, R., Yang, D. et al. Prescription of antipsychotic drugs by office-based physicians in the United States, 1989-1997. 2002; Psychiatric Services 53(4): 425-430. • Holt, R. and Peveler, R. Association between antipsychotic drugs and diabetes. 2006; Diabetes, Obesity and Metabolism 8: 125-135. • Kowatch, R., Fristad, M. et al. Treatment guidelines for children and adolescents with bipolar disorder: child psychiatric workgroup on bipolar disorder, 2005; J. Am. Acad. Child Adolesc. Psychiatry 44(3): 213-232. • Kumra, S., Briguglio, C. et al. Including children and adolescents with schizophrenia in medication-free research. 1999; Am J Psychiatry 156(7): 1065-1068. • Meltzer, H., McGurk, S. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. 1999; Schizophrenia Bulletin 25(2): 233-255.

21. References • Moore, C., Biederman, J. et al. Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a proton magnetic resonance spectroscopy study of the anterior cingulate cortex. 2007; J. Affect Disord 99(1-3): 19-25. • Olfson, M., Blanco, C. et al. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. 2006; Arch Gen Psychiatry 63: 679-685. • Pappadopulos, E., Jensen, P. et al. “Real world” atypical antipsychotic prescribing practices in public child and adolescent inpatient settings. 2002; Schizophrenia Bulletin 28(1): 111-121. • Raggi, M., Mandrioli, R. et al. “Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions. 2004; Current Medicinal Chemistry 11: 279-296. • Saxena, K., Chang, K. et al. Treatment of aggression with risperidone in children and adolescents with bipolar disorder: a case series. 2006; Bipolar Disorders 8: 405-410. • Shaw, P., Sporn, A. et al. Childhood-onset schizophrenia. 2006; Arch Gen Psychiatry 63: 721-730. • Sikich, L., Hamer, R. et al. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial. 2004; Neuropsychopharmacology 29: 133-145. • Sivaprasad, L., Hassan, T., Handy, S. Survey of atypical antipsychotic medication use by child and adolescent psychiatrists. 2006; Child and Adoles Mental Hlth 11(3): 164-167. • Taniguchi, T., Sumitani, S. et al. Effect of antipsychotic replacement with quetiapine on the symptoms and quality of life of schizophrenic patients with extrapyramidal symptoms. 2006; Hum Psychopharmacol Clin Exp 21: 439-445. • Vieweg, W., Sood, A. et al. Newer antipsychotic drugs and obesity in children and adolescents. How should we assess drug-associated weight gain? 2005; 111: 177-184. • West, L., Waldrop, J. Risperidone use in the treatment of behavioral symptoms in children with autism. 2006; Pediatric Nursing 32(6): 545-549. • Wooten, J. Metabolic effects of the atypical antipsychotics. 2007; Southern Medical J 100(8): 771-772. • Child and Adolescent Bipolar Foundation [www.bpkids.org] Retrieved on 12.3.07 • Rapid Cycling Bipolar Disorder [www.about.com] Retrieved on 2.28.08