Treatment of Acute Mania in Pediatric Bipolar Disorder

Assessing the Evidence

Stewart S. Newman MD

Senior Child Fellow

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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

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Discussion Case, cont’d

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

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Discussion Case, cont’d

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

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Discussion Case, cont’d

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.”

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Discussion Case, cont’d

Tells the evaluator repeatedly “You don’t want to do this, you know I’m 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”

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Discussion Case, cont’d

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

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“The Question”

“What evidence do we have to guide the treatment of acute mania in pediatric

bipolar disorder?”

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Levels of EvidenceLevel A: systematic review of RCTs with

narrow confidence intervalsLevel 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 appraisalAdapted from the US Preventive Services Task

Force 1996

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Searching the Literature

Online resources onlySearches on Medline, EMBase,

Cochrane, Up To Date, MD Consult, AACAP Website

Used keyword searches:Pediatric bipolar disorderPediatric maniaAcute mania treatment

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Selected Articles

M. N. Pavuluri et. al. “A Pharmacotherapy Algorithm for Stabilization and Maintenance of Pediatric Bipolar Disorder” JAACAP 43:7, 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

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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

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Pavuluri et. al. 2004

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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

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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

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Pavuluri et. al. 2004

Positives:Specific to the pediatric populationDevelopment of treatment algorithmDiscussion of level of evidence used

Negatives:Treatment not specific to acute maniaUse of three mood stabilizers, four

atypical antipsychotics

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Bourin et. al. 2005

Review of the literature regarding treatment of acute mania

Highlights the conceptual differences between the US and Europe

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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

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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

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Bourin et. al. 2005

Positives:Specific to treatment of acute maniaDiscusses available evidence in a

systematic fashionRecent review of the literature

Negatives:Not specific to childrenEmphasis on US vs Europe

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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

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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

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McClellan, Werry 1997

Positives:Focused on treatment of childrenSection on acute mania treatment Authority that establishes “standard of

care”

Negatives:38 pages long!Dated literature review with no recent

update available

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Conclusions

First line treatment for acute mania in children and adolescentsMood stabilizer: lithium or divalproexConsider carbamazepine second

Consideration of adjunctive treatmentAtypical antipsychotics, especially in

mania with psychosis or agitationPossibly antipsychotic monotherapy