Barclay Gr 11 19 08 Pediatric Bipolar Disorder Revised111708

Help for the Primary Care Physician Gregory P. Barclay, M.D. November 19, 2008 Pediatric and Adolescent Bipolar Disorder

Goals of Today’s Presentation
Discuss the current controversy surrounding pediatric bipolar disorder
Review the various clinical presentations of pediatric mood and behavior disorders
Discuss evaluation and treatment recommendations

What we aren’t going to discuss
The Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) specific criteria for Adult Bipolar Disorder
Neurobiological pathways, circuits, and brain structures thought to be related to mood dysregulation
Complex Psychopharmacological algorithms
If these interest you, email me and I will be happy to supply details: [email_address]

The Pediatric Bipolar Debate
Why has the diagnosis of Pediatric Bipolar Disorder (PBD)increased 40-fold from 1994-2003, e.g. 80,000 newly diagnosed patients in 2003 alone?
What truly constitutes PBD? Is there any consensus among the experts?
When there is a very poor concordance rate between parents and between parent+patient on pediatric manic symptoms, how valid is the diagnosis?
Does “My Kid’s Bipolar” become a way for parents or youths to excuse problematic/criminal behavior or avoid changing ineffective parental discipline?
What are the implications of diagnosing & aggressively medicating PBD, especially given the high rates of sub-threshold symptoms (5-15%) reported in general population studies?
Moreno et al., 2007

Clinical Quiz! Case #1
16 year old male, several year history of social anxiety with recent situational depression, started on Fluoxetine, 20 mg. daily 14 days ago, now with 7 day history of:
Decreased Need for Sleep
Grandiose Ideas - “Inventions I used dream about are now reality!”
Pressured Speech
Feels “super great” but now quick to anger, which is a distinct change from past demeanor
Positive Family History of Depression

6 year old male, history of hyperactivity, impulsivity, and chronic behavior problems including defiance and aggressive behavior, directed mainly at mother who is a single parent with 2 younger sons, ages 4 and 2, both with behavior problems.
Mother states he “can be loving one minute and hateful the next”. Moods are highly unpredictable and more labile since institution of Methylphenidate 8 months ago at urging of kindergarten teacher.
Trouble going to sleep at night, has trouble getting going in the morning. Awakens during the night to forage for food.
Biological father described as violent, abusive, and prone to methamphetamine addiction. Currently incarcerated for armed robbery.

14 year old female referred by therapist with note saying “needs medications for Bipolar Disorder”
Mother describes daughter as chronically unhappy and irritable, self-centered, impulsive, and drifting to a negative peer group. Smokes cigarettes and has used marijuana, drinks alcohol with peers. Seems chronically angry at her mother. Tends to isolate and self-mutilate when upset. Sexually promiscuous.
History of sexual abuse by stepfather, who is now incarcerated. Biological father’s whereabouts and history unknown. Mother abuses alcohol.
Describes her mood as angry unless she is with her boyfriend.

Will the Real Bipolar Patient Please Stand Up?
Each case marked by mood fluctuations
Each has a family history that raises some concerns
Each has psychosocial issues
Each has comorbid additional psychiatric disorders
Clinical Case #1
SSRI-induced hypomania
Clinical Case #2
Stimulant-induced mood disorder with stimulant rebound
Clinical Case #3
Possible PTSD vs. Personality Disorder, with substance abuse

Historically under-diagnosed or currently over-diagnosed?
Managed Care and Reimbursement Factors
PBD Diagnosis Significantly increased among African American Male and Caucasian Female Adolescents from 10% in 1996 to 36% in 2004
Coincides with decline in diagnoses of Conduct Disorder & various personality disorders (Borderline, Antisocial) Blader, et al., 2007
Popular press and marketing
“ Direct to Consumer” advertising
Direct Compensation paid to PBD researchers
“ Rebranding” of old drugs by pharmaceutical companies
“ Softening” of Diagnostic Criteria
The PBD Epidemic - Contributing Factors

Softening of Diagnostic Criteria
The DSM IV criteria were established pre-1994 and applied only to the adult forms of the illness (Bipolar I, Bipolar II and “Bipolar Disorder NOS”)
Post-1994 there has been a two-fold increase in reported prevalence of Bipolar II and Bipolar NOS diagnoses among the adult population, while prevalence of Bipolar I remains ca. 1%.
Now in 2008 there is consensus that the PBD is distinctly different from the adult presentations, but little agreement on proper diagnostic criteria. The great majority of children referred and treated do not fulfill current DSM IV criteria for Bipolar Disorder

Other Contributing Factors
Genetic Anticipation
Known clustering of certain disorders in families
Assortative Mating
Progressively earlier age of onset and increasing severity of illness in successive generations
“ Unstable DNA” &”Kindling”
Petronis, et al., 1995, Geller et al., 2006
Twin and Family Prevalence Rates support this theory
One Bipolar Parent, risk increases to 15-30%
Two Bipolar Parents, risk increases to 50-75%
Fraternal Twins 15-25%
Identical Twins 70%
Singh, 2008

The role of stimulating medications
Children who progress to develop PBD often present with depressive, anxious, or ADHD symptoms
These presentations encourage trials of antidepressant and stimulant medications
61% of cases of Treatment Emergent Mania (TEM) emerged after exposure to SSRI’s
Risk twice as high in girls vs. boys
Anxiety Symptoms significantly predicted TEM
1:10 children treated with SSRI’s display agitation and manic symptoms
36% TEM emerged after exposure to stimulant drugs
Faedda et al, 2004, Vitello, 2004
“ Stimulant Rebound” manifested by irritability, euphoria, sadness, crying, and insomnia occurred in 21% of children exposed to stimulant drugs Carlson et al., 2003

The Sad Truth
Children identified as having mood and behavior disturbances are increasingly common in American society.
These patients often will present to their primary care physician requesting treatment.
There is increased public awareness, information availability via the Internet, and expectation that complex, multi-factorial behavior and mood problems require medical treatment
There are growing numbers of non-physician mental health professionals who share this perspective and who will refer expecting medication
Patients with severe mood and behavior disorders in childhood DO go on to display significant impairment as adults
The shortage of child/adolescent psychiatric services in most areas will worsen for the foreseeable future, putting increased pressure on primary care physicians to evaluate and medicate

The Experts (and everyone else) agree on these points
PBD is a chronic disturbance manifested by rapid, continuous cycling of the mood
Majority of PBD children symptomatic for over 3 years at time of diagnosis
Most display daily cycling (“Ultradian cycling”, >365 cycles/yr)
Smaller percentage display “Ultrarapid cycling” (5-364 cycles/yr)
High rates of comorbidity with other conditions
Absence of clear cut episodes that follow good premorbid adjustment
These youth are chronically impaired in most measures of daily functioning
The more impaired children tend to have severe symptoms from earlier on, and tend to have a strong family history of mood disorders.

Comorbidity Issues
Comorbidity is the rule, not the exception
95% have comorbid ADHD
91% have comorbid Oppositional Defiant Disorder (ODD)
80% of preschoolers recently diagnosed with PBD have comorbid ADHD+ODD
69-74% have comorbid conduct disorder
Lesser but significant comorbidity with Pervasive Developmental Disorders and Tourette’s Disorder
Patients with very early onset of depression are at extremely high risk for PBD -- 48-61% switch from depression to PBD
Numerous reports of increased cycling or induction of mania when children or adolescents were exposed to antidepressants

Points of Disagreement that Muddy the Waters
The role of “Cardinal Symptoms” that best differentiate PBD from ADHD and other psychiatric disorders (Geller, et al.)
The value placed on accompanying symptoms that poorly differentiate BPD from other psychiatric disorders but seem to be highly prevalent in BPD nonetheless (Biederman, et al.)
Irritability
Rages (“Affective Storms”)
Hyperactivity
“ Irritability is as diagnostic of PBD as a sore throat is diagnostic of streptococcal pharyngitis” (e.g. 5%)
Geller, 2007

What, then are the “Cardinal Symptoms”?
5 symptoms most significantly differentiate PBD for ADHD & Controls (p<.0001)
Elated Mood
Grandiosity
Commonly see mood congruent, grandiose delusions
Most common hallucinations are auditory hallucinations
Decreased Need for Sleep
Flight of Ideas/Racing Thoughts
Hypersexuality
Geller et al., 2002

Cardinal Symptom Specifics
Elated children laugh hysterically & act infectiously happy out of context
Grandiose children will act as if the rules to not pertain to them; they are so smart they can tell teachers what to teach, etc. Delusions frequently involve special powers and beliefs
Flight of ideas : Ask whether topics of discussion change rapidly in an manner quite confusing to anyone listening
Racing thoughts : “It’s hard to do anything because my thoughts are distracting me”
Decreased need for sleep : Sleep 3-5 hrs & not tired the next day; up arranging furniture, talking on phone, etc. night after night
Hypersexuality has an erotic, pleasure-seeking quality to it, unlike the behavior of sexually abused children, which has an anxious/compulsive quality.
Singh, 2008

Clinical Features of Mania in PBD
Children experiencing mania or mixed states may be alternatively:
Demanding yet hilariously funny
Hostile and in despair at various times during any given day
Prone to intensive, seemingly uncontrollable rages during which time they may:
Damage property
Run away
Dash into a street without any thought of the consequences
Dysphoric Mania is most common prepubertally, while post-pubertal mania tends to follow a more adult-type pattern

Common but non-distinguishing symptoms
Poor judgment
Irritable mood
A distinct feature of irritability in PBD patients is extremely aggressive and/or self-injurious behavior
Accelerated Speech
Distractibility
Increased Energy
> 44% of ADHD children without PBD display these symptoms!
Geller and DelBello, 2006

ADHD and PBD - Key Differences Not seen Present Flight of Ideas/Racing Thoughts ADHD/ADD Bipolar/Depression Common Family History Rare Common Aggressive or suicidal behavior Less prominent Very prominent Irritable mood Not seen Common Psychotic Symptoms Not seen Common Hypersexuality Much less common Common Elevated Mood ADHD PBD Symptom

NIMH Roundtable Classification (2002)
“Narrow”
Full DSM IV Criteria for Mania
No debate as to diagnosis
“Intermediate”
Category I - Hallmark symptoms of short duration (1-3 days)
Category II - Episodic Irritable Mania without elation
“Broad”
Nonepisodic and chronic symptoms of severe irritability and hyperarousal
“ Affective Storms”
Severe Temper Outbursts
No elation, grandiosity, or hypersexuality
Leibenluft, 2002

The 8-year outcome study results
“ Narrow” phenotypes are similar to the sickest 20% of adult Bipolar Patients and tend to be severely and chronically impaired through childhood
Children with the “Broad” Phenotype represent the bulk of new referrals, yet there is now unequivocal evidence that they display a different clinical course with less impairment
In essence, this is the conclusion: Children with narrow phenotype grow into adults with severe Bipolar Disorder, while children with broader phenotypes grow into adults with impulse control and personality disorders
Geller et al, 2008

Evaluation Recommendations
Do a good assessment, including:
Establish a positive family history
Interview parents and child separately due to very poor concordance between parties
Use a rating scale such as the parent version of the Young Mania Rating Scale (YMRS); >13 = possible, >21=likely
2 week mood chart
Discontinue any psychiatric medication
Especially SSRI’s and Stimulants
Explain rationale to parents and prepare them
Wait 3-4 weeks before re-evaluating
Obtain a psychiatric consultation if at all possible

Medication issues
Very limited studies to date, most open label
As of 2005, only 5 published placebo controlled studies, but much research currently underway
Until 2007, only LiC03 was FDA approved for use in PBD (down to age 12)
Traditional mood stabilizers have not shown promising results - this is different from adults
Atypical Antipsychotics alone or in combination with mood stabilizers seem helpful
Risperidone and Aripiprazole recently FDA-approved for PBD

Medication Issues II
Response rates 33% to 50% at best!
Those that respond generally relapse quickly (>70%)
Most effective mood stabilizers = Valproate, LiC03, Carbamazepine
Most effective Atypical Antipsychotics = risperidone, aripiprazole, quetiapine, olanzapine, ziprasidone Pavuluri et al, 2004
Most studies have focused on treatment of manic or mixed symptoms; treatment of bipolar depression in children less effective
Lamotrogine, possibly Olanzapine+Fluoxetine

The dilemma with medications
They all have side effects:
Weight gain - Atypicals, Some Mood Stabilizers
Metabolic Syndrome - Atypicals
Prolactinomas - Atypicals
Polycystic Ovarian Syndrome - Depakote
Dyskinesias - Aripiprazole
Diminished Testosterone - Atypicals
Arrhythmias - Ziprasidone
Compliance often poor
Frequent dosing
Serum Monitoring

Other important interventions
Psychotherapy, especially Dialectical Behavior Therapy & Child/Family Focused Cognitive Behavior Therapy, has been shown to be highly effective (Pavuluri, et al.)
Immediate focus is on affect regulation and conjoint problem solving
Diminish parental criticism and rejection and increase maternal warmth
Maternal warmth single greatest predictor in maintaining remission (Geller, 2008)
Problem is: Finding a local therapist who even knows what Dialectical Behavior Therapy is, much less having had the training.
ECT for the most severe, non-responsive cases

Prevention Tips
Factors that predict the development of mania include:
Depression with rapid onset, psychomotor retardation, and psychosis
Family history of mood disorder, especially bipolar disorder
History of hypomania or mania with antidepressant treatment
Therefore, with any acutely depressed child or teen, it is critically important to obtain a detailed family history
If family history is positive, avoid antidepressants and refer!

Additional Pearls to remember
Diagnosis of PBD cannot be made if patient is taking SSRI’s or Stimulants, due to evidence that those agents trigger non-specific and possibly cardinal symptoms of PBD
Even a combination of mood stabilizers and atypical antipsychotics are effective in 50% of cases, at best
So, take your time, refer if you can, and make sure to stress the need for multi-modal intervention!

Support for Families
The Child and Adolescent Bipolar Foundation (CABF)
www.bpkids.org
Information and education
Depression and Bipolar Support Alliance (DBSA)
www.dbsalliance.org
National Alliance for the Mentally Ill (NAMI)
www.nami.org
National Institute of Mental Health (NIMH)
www.nimh.nih.gov

Summing it up
There is ample evidence to support the presence of PBD but the diagnostic criteria are still uncertain
The extensive use of antidepressant and stimulant drugs in children and teens has clearly contributed to the explosion of referrals with the “Broad” phenotype classification
Most recent outcome studies suggest that the “Broad” sub-type of PBD is currently over-diagnosed, raising questions about the appropriateness of utilizing antipsychotic medications in this group
There is a desperate need for rigorous controlled studies to establish clear diagnostic and treatment criteria

Questions & Comments

Barclay Gr 11 19 08 Pediatric Bipolar Disorder Revised111708

by gpbmd on Oct 29, 2009

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Barclay Gr 11 19 08 Pediatric Bipolar Disorder Revised111708 — Presentation Transcript