Pediatric Bipolar Disorder Incidence Trends And Pharmacotherapy Best
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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...

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 Presentation Transcript

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