Pediatric Bipolar Disorder Incidence Trends And Pharmacotherapy Best


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A population and a disease state that some still think should not go together. The data suggests otherwise...

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Pediatric Bipolar Disorder Incidence Trends And Pharmacotherapy Best

  1. 1. Pediatric Bipolar Disorder Incidence Trends And Pharmacotherapy Best Practices Clinical Insight Regarding A Misunderstood Mental Illness in the Pediatric Population John W. Probst, MPH 4 th Year Pharm.D. Student USC School of Pharmacy March 25, 2009
  2. 2. Agenda <ul><li>Provide presentation objectives </li></ul><ul><li>Epidemiological background </li></ul><ul><li>Researched pharmacotherapy treatments </li></ul><ul><li>Clinical treatment best practices </li></ul><ul><li>Summary and Q & A </li></ul>
  3. 3. Objectives <ul><li>Provide epidemiological background regarding the incidence of pediatric bipolar disorder (BD) </li></ul><ul><li>Discuss findings in the literature that support various psychotropic treatment approaches </li></ul><ul><li>Synthesize pharmacotherapy research findings and clinical practice as to which treatment approach works best for this patient population </li></ul>
  4. 4. Epidemiological Background
  5. 5. Statistical Overview <ul><li>Historical studies show BD prevalence to be only 0.1-1.0% in pediatric population </li></ul><ul><li>Incidence rates in the past 10 years have: </li></ul><ul><ul><li>Doubled in outpatient clinical settings (up to 6%) </li></ul></ul><ul><ul><li>Quadrupled in community hospitals (up to 40%) </li></ul></ul><ul><li>Number of psychiatric office visits for youth with BD has  40x in past decade </li></ul><ul><li>Adult BD retrospective: 60% had onset of sxs <20 yo, while 10% had onset of sxs <10 yo </li></ul>
  6. 6. Diagnostic Clarity <ul><li>Allows for a clearer understanding of BD s/sxs in young people </li></ul><ul><li>Different and better defined, age-specific diagnostic criteria </li></ul><ul><li>Clinicians can diagnose and treat with more confidence </li></ul>
  7. 7. Operation “Correct Diagnosis” <ul><li>Alarming  in diagnoses has caused concern: </li></ul><ul><ul><li>Is the differential diagnosis accurate? </li></ul></ul><ul><ul><li>Have comorbid mental/behavioral disorders been accounted for and also fully characterized? </li></ul></ul><ul><ul><li>Is the most appropriate pharmacotherapy approach being employed to treat the patient, not just sxs? </li></ul></ul><ul><li>Number of guided research/studies have risen dramatically, as reflected by an  in interest within medical community re: BD in youth </li></ul>
  8. 8. Comorbid Confounders <ul><li>Mental/behavioral D/O can complicate the dx (e.g. autism, ODD, etc.) </li></ul><ul><li>Research continues to elucidate differences between BD & ADHD </li></ul><ul><li>Other disorders are relatively common in children with BD </li></ul>
  9. 9. Era of Assessment Tools <ul><li>Currently, ten (10) publications are available that are commonly used when assessing pediatric BD </li></ul><ul><ul><li>Only two (2) publications were specifically designed to assess BD in a pediatric population. Tools used: </li></ul></ul><ul><ul><ul><li>K-SADS = Schedule for Affective Disorders and Schizophrenia for School-Age Children </li></ul></ul></ul><ul><ul><ul><li>MRS = Mania Rating Scale </li></ul></ul></ul><ul><ul><ul><li>CMRS = Child Mania Rating Scale </li></ul></ul></ul><ul><li>Most important epidemiological development for this disease and population (i.e. real dx basis) </li></ul>
  10. 10. Key Population Findings <ul><li>Smoking and/or substance use is positively correlated to pediatric BD (no causation proved) </li></ul><ul><li>Young people with BD are more likely to be overweight or obese than the adults with BD </li></ul><ul><li>Monotherapy for pediatric BD patients is rarely effective when comorbid conditions exist </li></ul><ul><li>More youth suffer from mixed episodes and cyclothymia, making BD dx and tx difficult </li></ul><ul><li>Risk of suicide and/or violence is very high </li></ul>
  11. 11. Researched Pharmacotherapy Treatments
  12. 12. Medication Usage Breakdown PURSUIT of EFFICACY
  13. 13. Historical Drugs of Choice <ul><li>Lithium carbonate – only FDA approved medication to treat BD in kids >13 yo </li></ul><ul><li>Divalproex and quetiapine </li></ul><ul><ul><li>popular combo treatment approach for poor & non-responders to lithium (other atypicals used too) </li></ul></ul><ul><ul><li>commonly used for acute tx of mania/mixed episodes </li></ul></ul><ul><li>Third line and beyond – Stimulants, SSRIs, other antidepressants (including TCAs), FGAs, SGAs, lamotrigine, CBZ and even BZDs </li></ul>TRIAL and ERROR
  14. 14. Drugs of Study - Gabapentin <ul><li>Dose studied = 900-2400mg/day </li></ul><ul><li>Best results for “rapid cyclers” & refractory pts </li></ul><ul><li>Patients responded well as evident by improved mood, appetite and only moderate weight gain </li></ul><ul><li>1 pt d/c drug experienced irritability and strong mood swings (was concurrently on stimulant) </li></ul><ul><li>Touted for safe, easily tolerated, low DDIs profile, while showing strong efficacy </li></ul>
  15. 15. Drugs of Study - Topiramate <ul><li>Few studies in pediatrics due to poor results in adult population (i.e. sampling bias) </li></ul><ul><li>Young Mania Rating Scale (YMRS) assessment tool used – helped show greatest baseline Δ </li></ul><ul><li>Studied as acute treatment only – no quality data re: long-term maintenance tx was found </li></ul><ul><li>Main drawback for most studies is small sample size – achieving statistical significance is hard </li></ul>
  16. 16. Drugs of Study - Combos <ul><li>“Best” results are with lithium, divalproex and an adjunct of choice (e.g. stimulant, SGA, etc.) </li></ul><ul><li>Another successful “cocktail” was risperidone + either lithium or divalproex – especially BD I </li></ul><ul><li>Many studies show improved mood when BOTH lithium and divalproex were on board </li></ul><ul><li>Body of research continues to show that mono-therapy for pediatric BD patients does not work </li></ul>
  17. 17. Tx Research Shortcomings <ul><li>Insufficient and limited data – information gaps </li></ul><ul><li>Studies have been small, inadequately designed & aren’t always longitudinal </li></ul><ul><li>Very little data focusing on maintenance treatment </li></ul><ul><li>Maintenance medication compliance and refining of regimens are poorly researched topics </li></ul>
  18. 18. Pharmacotherapy Challenges <ul><li>Tailor treatment regimens for acute and especially chronic BD in pediatrics </li></ul><ul><li>Determine best therapy for mania & depression </li></ul><ul><li>Provide tx algorithms for providers dealing with complicated patients </li></ul><ul><li>Coordinate drug therapy with CBT programs - key for maint/euthymia </li></ul>
  19. 19. Clinical Treatment Best Practices
  20. 20. Today’s Working Standard <ul><li>Treatment is largely determined by phenotype </li></ul><ul><ul><li>Varies by country based on diagnostic criteria </li></ul></ul><ul><ul><li>Becoming increasingly dependent on assessment tools </li></ul></ul><ul><ul><ul><li>CBCL-BD = Child Behavior Checklist for BD </li></ul></ul></ul><ul><ul><ul><li>YMRS = Young Mania Rating Scale </li></ul></ul></ul><ul><li>Clinicians are beginning to categorize pediatric BD as either “narrow” or “broad” to guide tx(s) </li></ul><ul><li>Acute mania = mood stabilizer and/or SGA </li></ul><ul><ul><li>Lithium is favored in children; divalproex in teens </li></ul></ul><ul><ul><li>Stimulants and other adjuncts are tolerated well </li></ul></ul>
  21. 21. The Role of Psychotherapy <ul><li>Best when entire family is involved upon diagnosis </li></ul><ul><li>Current approaches include: </li></ul><ul><ul><li>FFT = family focused treatment </li></ul></ul><ul><ul><li>IFT = individual family treatment </li></ul></ul><ul><ul><li>MFPG = multifamily psychoeducation groups </li></ul></ul><ul><li>CBT is a mainstay treatment and data shows great benefit in controlling sxs of mania and depression long term </li></ul>
  22. 22. One Regimen Fits All? <ul><li>Further delineation and customization of diagnosis and treatment – why not cookie cutter? </li></ul><ul><ul><li>Providers can establish a meaningful prognosis </li></ul></ul><ul><ul><li>Interventions made at subsyndromal or early stages </li></ul></ul><ul><li>Genetic and neuroimaging methodologies are starting to reveal a potentially wide array of etiologies (i.e. BD “spectrum”) </li></ul><ul><li>Questions re: who should receive monotherapy vs. combo, and when to modify therapy, still remain </li></ul>
  23. 23. Focus on Prognosis Goals <ul><li>Quality of life and long term health are starting to become as important as controlling acute sxs </li></ul><ul><ul><li>Determine role/extent of SGAs in weight gain, etc. </li></ul></ul><ul><ul><li>Emphasis on managing other comorbid conditions to maximize drug efficacy and improve pt outlook </li></ul></ul><ul><li>Determine longitudinal course of BD in order to guide patient through transition to adulthood </li></ul><ul><li>Stress appropriate medication utilization, while minimizing cost burden & ADRs - not so in past </li></ul>
  24. 24. Summary
  25. 25. Much More to Learn… <ul><li>As understanding increases about the pediatric BD population, better diagnostic tools and treatment approaches are being developed </li></ul><ul><li>Drug therapy for pediatric BD is starting to be directed by better “trials”, hence fewer “errors” </li></ul><ul><li>Customizing pharamcotherapy is still a work in progress for: 1) acute vs. chronic; 2) mania/mixed vs. depression; and 3) comorbid vs. lone disorder </li></ul><ul><li>Proper tx is critical for long-term  QOL!! </li></ul>
  26. 26. Medication Breakdown <ul><li>Current DOC </li></ul><ul><ul><li>Divalproex (mania * ) </li></ul></ul><ul><ul><li>Lamotrigine (depression * ) </li></ul></ul><ul><ul><li>SGAs </li></ul></ul><ul><ul><ul><li>Risperidone </li></ul></ul></ul><ul><ul><ul><li>Quetiapine </li></ul></ul></ul><ul><ul><ul><li>Ziprasidone/Aripiprazole </li></ul></ul></ul><ul><ul><ul><li>Clozapine/Olanzapine - REF </li></ul></ul></ul><ul><ul><li>Topiramate </li></ul></ul><ul><ul><li>Gabapentin </li></ul></ul><ul><ul><li>Carbamazepine </li></ul></ul><ul><li>Others still in use </li></ul><ul><ul><li>Lithium (depression * ) </li></ul></ul><ul><ul><li>Oxcarbazepine </li></ul></ul><ul><ul><li>Stimulants (SR is best) </li></ul></ul><ul><ul><li>FGAs </li></ul></ul><ul><ul><li>Antidepressants </li></ul></ul><ul><ul><ul><li>Trazadone </li></ul></ul></ul>based on efficacy in adults - new studies support use in youth <ul><ul><li>* general consensus/some data </li></ul></ul>
  27. 27. Any Questions?
  28. 28. References <ul><li>Castilla-Puentes R. Multiple episodes in children and adolescents with bipolar disorder: comorbidity, hospitalization, and treatment (data from a cohort of 8,129 patients of a national managed care database). International Journal of Psychiatry in Medicine . 2008. 38(1):61-70. </li></ul><ul><li>Demeter CA, et al. Current research in child and adolescent bipolar disorder. Dialogues in Clinical Neuroscience . 2008. 10(2):215-28. </li></ul><ul><li>Goldstein BI, et al. Preliminary findings regarding overweight and obesity in pediatric bipolar disorder. Journal of Clinical Psychiatry . Dec 2008. 69(12):1953-9. </li></ul><ul><li>Goldstein BI, et al. Significance of cigarette smoking among youths with bipolar disorder. American Journal on Addictions . Sep-Oct 2008. 17(5):364-71. </li></ul><ul><li>Hamrin V, Pachler M. Pediatric Bipolar Disorder: Evidence-Based Psychopharmacological Treatments. Journal of Child and Adolescent Psychiatric Nursing. Feb 2007. 20:1; Psychology Module p.40. </li></ul><ul><li>Holtmann M, et al. Rapid increase in rates of bipolar diagnosis in youth: &quot;true&quot; bipolarity or misdiagnosed severe disruptive behavior disorders? Archives of General Psychiatry . Apr 2008. 65(4):477. </li></ul>
  29. 29. References <ul><li>Leibenluft E, Rich BA. Pediatric Bipolar Disorder. Annual Review of Clinical Psychology. 2008. 4:163–87. </li></ul><ul><li>Masi G, et al. Comorbidity of conduct disorder and bipolar disorder in clinically referred children and adolescents. Journal of Child & Adolescent Psychopharmacology . Jun 2008. 18(3):271-9. </li></ul><ul><li>Miklowitz DJ, et al. Family-focused treatment for adolescents with bipolar disorder: results of a 2-year randomized trial. Sep 2008. Archives of General Psychiatry . 65(9):1053-61. </li></ul><ul><li>Munesue T, et al. High prevalence of bipolar disorder comorbidity in adolescents and young adults with high-functioning autism spectrum disorder: a preliminary study of 44 outpatients. Journal of Affective Disorders . Dec 2008. 111(2-3):170-5. </li></ul><ul><li>Pavuluri MN, Naylor MW. Multi-Modal Integrated Treatment for Youth With Bipolar Disorder. Psychiatric Times . May 2005. 22 (6). </li></ul><ul><li>Pavuluri MN, et al. Pediatric Bipolar Disorder: A Review of the Past 10 Years. Journal of American Academy of Child and Adolescent Psychiatry . 2005. 44(9):846-871. </li></ul>
  30. 30. References <ul><li>Ryback RS, et al. Letters to Editor – Gabapentin in Bipolar Disorder. Journal of Neuropsychiatry & Clinical Neurosciences . 9 (2): 301. </li></ul><ul><li>Singh, T. Pediatric Bipolar Disorder: Diagnostic Challenges in Identifying Symptoms and Course of Illness. Jun 2008. </li></ul><ul><li>Wilens TE, et al. Further evidence of an association between adolescent bipolar disorder with smoking and substance use disorders: a controlled study. Drug & Alcohol Dependence . Jun 2008. 95(3):188-98. </li></ul>