Bipolar: To Be or Not To Be… Pediatric Bipolar Update
Stephen Grcevich, MD
President and Founder, Family Center by the Falls Chagrin Falls, OH
Department of Psychiatry Northeastern Ohio Universities College of Medicine
Presented at: Children’s Hospital Medical Center of Akron August 20, 2010
E-mail: [email protected] Phone: (440) 543-3400 Twitter: @drgrcevich
Educational objectives:
Familiarize health care professionals with current information regarding the diagnosis of Bipolar Disorder in Children
Review recent evidence-based literature regarding Bipolar Spectrum Disorders
Identify treatment options, including medication management, of mood disorders in children
Pharmaceutical Industry Consulting:
Shire US (100% of compensation donated to
charity since 1/1/08)
Grant/Research Support
Child and Adolescent Psychiatry Trials (CAPTN)
Network-ASK, PARCA, NOTA studies funded through NIMH
Speakers’ Bureaus None since 2006
Other Financial/Material Support
Web MD/MedscapeLeerink-Swann
Major Shareholder None
Stephen Grcevich, MD: disclosures:
The greatest controversy in our field?
40X increase in outpatient visits for pediatric bipolar disorder between 1994-95 and 2002-03 (6X increase in prevalence of bipolar diagnosis)
The majority of kids receiving the diagnosis don’t meet traditional DSM-IV criteria for the disorder
Average number of psychotropic medications: 3.4
Average number of medication trials: 6.3 (+/- 3.7)
Medications approved for pediatric bipolar disorder associated with rapid, large increases in weight, lipid, cholesterol elevation, Type 2 diabetes
Moreno C, Laje G, Blanco C, et al. Arch. Gen. Psychiatry 64, 1032–1039 (2007).
Weight gain in antipsychotic naïve pediatric patients:
Correll, CU et al., JAMA. 2009;302:1765–1773.
Metabolic effects of second-generation antipsychotics in
pediatric patients:Agent: Metabolic Effects:Olanzapine fasting glucose
insulininsulin resistance
Quetiapine total cholesteroltriglyceridesHDL cholesteroltriglyceride:HDL ratio
Risperidone triglyceridesAripiprazole No significant metabolic effects
Correll, CU et al., JAMA. 2009;302:1765–1773.
Diagnostic criteria for Bipolar Disorder:
A distinct period of elevated, expansive or irritable mood lasting at least one week in which three or more of the following are present (four if mood is only irritable):
Inflated self-esteem, grandiosity
Decreased need for sleep
Pressured speech
Flight of ideas, racing thoughts
Increased distractibility
Increased goal-directed activity (psychomotor agitation)
Involvement in pleasurable behaviors with potential for painful consequences
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR)
Diagnostic criteria for Bipolar Disorder:
Mixed episodes: symptoms of mania and depression last at least seven days
Bipolar II: major depression and hypomania last at least four days
Rapid Cycling: four or more full episodes in a calendar year
Bipolar NOS: cases that don’t meet criteria for other bipolar conditions…the majority of pediatric cases
*Ultrarapid Cycling: brief, frequent episodes lasting from a few hours to less than four days
*Ultradian Cycling: cycles last minutes to hours, >365 cycles/year
*Condition not listed in DSM-IV
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR)
Comorbidity and pediatric bipolar disorder:
ADHD: 90% in children with bipolar disorder, 60% in teens with bipolar disorder, 13% in adults with bipolar disorder
Prevalence of anxiety disorders: 56-76%
Increased substance abuse risk-greater risk in adolescent-onset vs. childhood onset BPD
4X greater risk of post-traumatic stress disorder
Joshi G, Wilens T. Child Adolesc Psychiatric Clin N Am 18 (2009) 291–319
Differentiating between ADHD and BPD in early adolescence:
SymptomSymptom
BPDBPD(n=60)(n=60)
%%
ADHDADHD(n=60)(n=60)
%% P ValueP Value
Elated moodElated mood 86.786.7 55 0.0010.001
GrandiosityGrandiosity 8585 6.76.7 0.0010.001
HypersexualityHypersexuality 4545 8.38.3 0.0010.001
Decreased need for Decreased need for sleepsleep 43.343.3 55 0.0010.001
Racing thoughtsRacing thoughts 48.348.3 00 0.0010.001
HyperenergeticHyperenergetic 96.796.7 91.791.7 0.440.44
DistractibilityDistractibility 91.791.7 9595 0.720.72
Geller et al. J Affect Disord. 1998;51:81.Geller B, Luby J. J Am Acad Child Adolesc Psychiatry (1998): 37(10) 1005
Differential diagnosis of pediatric bipolar disorder :
Medical/neurologic concerns (iatrogenic)
ADHD/Conduct Disorder
Anxiety disorders
Psychotic disorders
Substance use disorders
Borderline Personality Disorder (and other Cluster B conditions)
Environmental, psychosocial, parenting factors
The center of the controversy:
There’s a large group of kids who demonstrate:
Irritability as their predominant mood state
Problems with emotional self-regulation often resulting in aggression
Problems with attention, concentration, academic performance
“At-risk” behaviors…self-injury, substance use, suicidal threats
Temper Dysregulation Disorder (TDD) with Dysphoria (proposed in
DSM-V): Characterized by severe recurrent temper outbursts in response to
common stressors
Temper outbursts are manifest verbally and/or behaviorally, such as in the form of verbal rages, or physical aggression towards people or property
The reaction is grossly out of proportion in intensity or duration to the situation or provocation
Responses inconsistent with developmental level
Temper outbursts occur, on average, three or more times per week.
Mood between temper outbursts is persistently negative (irritable, angry, and/or sad).
Negative mood is observable by others (e.g., parents, teachers, peers).
DSM-V Task Force, American Psychiatric Association, 2010
AACAP concerns about “TDD”
Diagnosis Is imprecise
Syndrome based on work in patients described as “SMD”
Invites criticism for “pathologizing” temper tantrums
Proposed criteria are almost certainly premature
Research hasn’t clarified boundaries between “TDD”, ADHD, Oppositional Defiant Disorder and developmentally acceptable behavior
More information needed on how the phenotype changes over the lifespan
American Academy of Child and Adolescent Psychiatry, March 30, 2010
What will kids with SMD/TDD look like in your clinic?
They have ADHD
They have difficulty with transitions
They tend to “ruminate”…indecisive, think too much about things, perseverate
They may experience some improvement in some settings from ADHD medication, but become more irritable, have more meltdowns at home
They have a higher than expected prevalence of anxiety disorders, but are probably subsyndromal for OCD
They’re prone to behavioral activation on SSRIs, often mistaken for mania, hypomania
AACAP Practice Parameters for Assessment and Treatment of Bipolar Disorder (2007)
Pharmacotherapy is the primary treatment in well-defined DSM-IV Bipolar I disorder
A comprehensive treatment plan, combining medications with psychotherapeutic interventions is needed to address the symptomatology and confounding psychosocial factors found in children and adolescents with bipolar disorder
J . Am. Acad. Child Adolesc. Psychiatry, 46:1, January 2007
FDA-approved medications for youth with Bipolar Disorder
Risperidone: Bipolar mania (10-17)
Aripiprazole: Bipolar mania (10-17)
Quetiapine: Bipolar mania (10-17)
Olanzapine: (labeling-consider other drugs first) Bipolar mania (13-17)
Lithium Carbonate: Bipolar mania (12-17)
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM193200.pdf
Second generation antipsychotics in pediatric bipolar disorder:
As of July, 2010: 26 studies published, including 5 RCTs (but several others completed)-all RCTs published in 2007 or later
Response rates in acute RCTs 45-89%, remission achieved in 25-72%
Treatment-refractory nature of patients enrolled at academic medical centers attenuated magnitude of AEs
Little data examining long-term course on SGAs, efficacy in preventing relapse
Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088.
Lithium in pediatric bipolar disorder:
One acute RCT: Li>PBO (46% response rate vs. 8%)
Didn’t appear to prevent relapse
Negative RCT in SMD
Narrow therapeutic window, toxicity in overdose concerns in adolescents
Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088
Anticonvulsants in pediatric bipolar disorder:
Divalproex sodium: open-label studies have demonstrated response rates of 56-92%, but two RCTs have failed to demonstrate efficacy
Lamotrigine: Three open-label studies suggest 50-60% remission rates, helpful with bipolar depression results confounded by adjunct meds
Topiramate, oxcarbazepine: Negative RCTs
Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088
Strategies for treating ADHD with comorbid Bipolar
Disorder: Effective mood stabilization may be necessary
before patients will respond to stimulants
Stimulants will be used in combination with mood stabilizers/antipsychotics
Many patients have histories of failed stimulant trials, or use of high doses of stimulant before bipolar disorder identified
RCT: Mixed amphetamine salts highly effective for ADHD in patients who had achieved mood stabilization on divalproex
Scheffer R et al. Am J Psychiatry (2005) 162:58-64
Psychotherapy/psychosocial treatment:
Multi-family psychoeducational groups: 1 RCT (N=35), families did better, no effect on severity of child’s mood symptoms
IFP (Individual/family psychoeducation) 1 RCT (N=20) improved children’s mood symptoms
FFT (Family focused therapy) psychoeducation, communication enhancement training, and problem solving skills training-two year RCT indicated improvement in depressive sx. With bipolar disorder
DBT: One open label trial (N=10)
CFF-CBT: Open-label trial (N=34) with three year follow-up showed benefits of treatment were maintained
West A, Pavuluri M. Child Adolesc Psychiatric Clin N Am 18 (2009) 471–482
Take-home points:
Use of the term “Bipolar Disorder” in pediatric population should be reserved for mood episodes lasting four days or longer
A large subset of patients exists with chronic irritability, explosive outbursts, chronic negativism, long-term risk of ADHD, depression, differences in neural circuitry and cognitive flexibility. Little research is available to inform our treatment of them.
Careful evaluation and a comprehensive treatment plan developed by a fully trained child and adolescent psychiatrist, combining medications with psychotherapeutic interventions, are essential
Resources for pediatricians:
AACAP Bipolar Disorder Resource Center http://www.aacap.org/cs/BipolarDisorder.ResourceCenter
Child and Adolescent Bipolar Foundation http://www.bpkids.org/
Psychopharmacology of Pediatric Bipolar Disorder Expert Review of Neurotherapeutics http://www.medscape.com/viewarticle/724852 (Medscape membership required-membership, article free. Click on print version for summary tables of all studies)
Questions?