Treatment of Acute Mania in Pediatric Bipolar Disorder

1
Treatment of Acute Mania in Pediatric Bipolar
Disorder

• Assessing the Evidence
• Stewart S. Newman MD
• Senior Child Fellow

2
Discussion Case

• 16 y/o WF with hx of bipolar disorder presents to
  the PES in the custody of AA police
• Reportedly was in a physical altercation with a
  fellow student at Pioneer HS
• Police indicate she was combative and belligerent
  towards them upon initial contact

3
Discussion Case, contd

• Patient is followed by a Child Fellow in the
  Commonwealth outpatient clinic
• Previously treated with divalproex and
  risperidone in combination
• Records indicate she has missed her last three
  appointments, and her medication supply should
  have been exhausted two months ago

4
Discussion Case, contd

• Per the outpatient treatment notes, the patient
  has been hospitalized once previously for
  suicidal ideation
• The patient has a history of intermittent
  cannabis and alcohol abuse
• There is a family history of bipolar disorder in
  a paternal grandfather

5
Discussion Case, contd

• On initial assessment, she is hyperverbal, giddy
  and expansive, but can rapidly become angry and
  belligerent with staff
• She is unable to give an account of the
  altercation at school, simply stating The bitch
  deserved it.

6
Discussion Case, contd

• Tells the evaluator repeatedly You dont want to
  do this, you know Im too important to be put
  through this.
• When stopped by the police officer from leaving
  PES, she begins to make sexualized comments
  towards him regarding being handcuffed

7
Discussion Case, contd

• The patient becomes combative with staff members,
  tries to elope and Security responds to PES
• The patient is placed in the seclusion suite due
  to elopement risk
• She is refusing any medication to calm her or
  organize her thoughts

8
The Question

• What evidence do we have to guide the treatment
  of acute mania in pediatric bipolar disorder?

9
Levels of Evidence

• Level A systematic review of RCTs with narrow
  confidence intervals
• Level B systematic review of cohort studies with
  homogeneity, individual cohort study, or low
  quality RCT outcomes studies
• Level C systematic review of case-control
  studies, individual case control studies, case
  series, and expert opinions with explicit
  critical appraisal
• Adapted from the US Preventive Services Task
  Force 1996

10
Searching the Literature

• Online resources only
• Searches on Medline, EMBase, Cochrane, Up To
  Date, MD Consult, AACAP Website
• Used keyword searches
• Pediatric bipolar disorder
• Pediatric mania
• Acute mania treatment

11
Selected Articles

• M. N. Pavuluri et. al. A Pharmacotherapy
  Algorithm for Stabilization and Maintenance of
  Pediatric Bipolar Disorder JAACAP 437, July
  2004
• M. Bourin, O. Lambert and B. Guitton Treatment
  of Acute Mania- from clinical trials to
  recommendations for clinical practice Human
  Psychopharmacology 20, 2005
• J. McClellan and J. Werry AACAP Practice
  Parameters for the Assessment and Treatment of
  Children and Adolescents with Bipolar Disorder
  JAACAP 1997

12
Pavuluri et. al. 2004

• Developed and studied a treatment algorithm for
  stabilization and maintenance of pediatric
  bipolar disorder
• Two phases of treatment- goal of the first phase
  was mood stabilization
• Discussed evidence used for development of the
  algorithm

13
Pavuluri et. al. 2004
14
Pavuluri et. al. 2004

• Noted Level B studies in children indicate mood
  stabilizers as the primary agents
• Lithium or divalproex as first line agents,
  followed by carbamazepine

15
Pavuluri et. al. 2004

• Good evidence for addition of atypical
  antipsychotic agent for more severe or psychotic
  mania cases
• Atypical antipsychotic agent monotherapy first
  line for predominant irritability or aggression

16
Pavuluri et. al. 2004

• Positives
• Specific to the pediatric population
• Development of treatment algorithm
• Discussion of level of evidence used
• Negatives
• Treatment not specific to acute mania
• Use of three mood stabilizers, four atypical
  antipsychotics

17
Bourin et. al. 2005

• Review of the literature regarding treatment of
  acute mania
• Highlights the conceptual differences between the
  US and Europe

18
Bourin et. al. 2005

• Discusses individual medications (mood
  stabilizers, antipsychotics, and benzodiazepines)
  alone and in combinations
• Also discusses efficacy of certain agents, forms
  of mania that predict treatment response, and
  alternate agent choices in a systematic manner

19
Bourin et. al. 2005

• Recommends first line use of mood stabilizers
  lithium and divalproate, with carbamazepine as
  second line
• Also recommends use of atypical antipsychotics as
  monotherapy or adjunct to mood stabilizer
  treatment
• Discussed use of third gen anticonvulsants in
  detail

20
Bourin et. al. 2005

• Positives
• Specific to treatment of acute mania
• Discusses available evidence in a systematic
  fashion
• Recent review of the literature
• Negatives
• Not specific to children
• Emphasis on US vs Europe

21
McClellan, Werry 1997

• Practice Parameters series represent exhaustive
  review of the available literature and expert
  concensus
• Specific section regarding treatment of acute
  manic symptoms
• Explicitly discusses rationale for choice of
  medication

22
McClellan, Werry 1997

• Recommend mood stabilizers (lithium and
  divalproex) as first line agents
• Carbamazepine recommended as second line mood
  stabilizer
• Adjunctive treatment with atypical antipsychotics
  or benzodiazepines may be necessary

23
McClellan, Werry 1997

• Positives
• Focused on treatment of children
• Section on acute mania treatment
• Authority that establishes standard of care
• Negatives
• 38 pages long!
• Dated literature review with no recent update
  available

24
Conclusions

• First line treatment for acute mania in children
  and adolescents
• Mood stabilizer lithium or divalproex
• Consider carbamazepine second
• Consideration of adjunctive treatment
• Atypical antipsychotics, especially in mania with
  psychosis or agitation
• Possibly antipsychotic monotherapy