PEDIATRIC POTPOURRI
From the 8th Annual Psychiatry Review—Youth Mental Health: Bridging Research and Clinical Practice, presented by
the University of Minnesota Medical School
| SCHIZOPHRENIA IN YOUTH —S. Charles Schulz, MD, Professor and Head, Department of Psychiatry, University of
Minnesota Medical School, Minneapolis
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| Significance of early stages of schizophrenia: duration of untreated psychosis (DUP; not same as prodrome) averages 1 yr
and is related to social, functional, and symptomatic outcome; reducing DUP may reduce severity of illness when treatment
starts; possibly fewer suicides in regions with early recognition programs; theoretically, early recognition can lead
to better utilization of resources
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| Duration of psychosis and outcomes in first-episode schizophrenia: in study, longer duration of psychotic symptoms or
of prodrome resulted in longer time to, and lower level of, remission
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| Special issues in treating youth with psychotic illnesses: no data on use of antipsychotic medications in young people, so
clinician must try to extrapolate adult data to youth; dosing strategies different in youth; in youth, side effects may be
more pronounced than, and/or different from, those in adults; specialized psychoeducational approaches indicated; teenagers
appear to be more susceptible than adults to metabolic side effects
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| Family issues in adolescent schizophrenia: at outset, parents generally ignorant about schizophrenia and confused about
where to get help (most start by seeking help from school or pediatrician); patient and family in shock and denial during
early treatment; concern about medications (especially about how long child will have to take them) and side effects
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| Functional Imaging for Research in Schizophrenia Treatment (FIRST) program: designed to provide expert assessment
of patients at outset of illness and to link results of research to clinical care; patients and staff develop relationships
that support longitudinal research; FIRST clinics provide infrastructure for clinical trials that will enhance options for patients
and families
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| Differentiating schizophrenia from bipolar disorder: similarities found in symptomatology, genes associated with risk,
and symptomatic responses to medications; differences observed in, eg, responses to some mood-stabilizing medications,
certain genes associated with risk, outcomes; multiple measures must be used to differentiate schizophrenia from bipolar
illness; speaker’s small pilot study looked at 22 measures of neuropsychologic testing and 23 imaging variables, and
found 12 of 45 measures could be used to obtain correct diagnoses; replication of results required
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| Magnetoencephalography (MEG): electrical testing of brain coherence and function; in early tests, researchers able to
separate Alzheimer’s disease from schizophrenia (with 100% accuracy); results must be replicated, then tested to determine
whether MEG equally useful in differentiating schizophrenia from bipolar disorder
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| Conclusions: similarities and differences between schizophrenia and bipolar disorder enigmatic; studying teenagers provides
opportunity to assess patients before long-term medication or other aspects of illness take effect; use of multiple
measures may assist in comparison of schizophrenia and bipolar disorder and provide clues to differentiating features
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| BIPOLAR DISORDER IN YOUTH —Joel V. Oberstar, MD, Assistant Professor, Department of Psychiatry, and Associate
Director, Child and Adolescent Psychiatry Fellowship, University of Minnesota Medical School
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| Introduction: shown that bipolar disorder does exist in children and adolescents, but manifests differently than in adults; in
children, course tends to be indolent and chronic; in adolescents, course more like that in adults; key symptoms that aid in
diagnosis include elated/expansive mood, decreased need for sleep (not to be confused with problems sleeping), flight of
ideas, and hypersexuality; comorbidity is rule, not exception; diagnosis of bipolar disorder “high-stakes decision” because
administering wrong medications (eg, stimulant or antidepressant) may exacerbate condition; also, bipolar disorder
requires “big guns” medications, such as antipsychotics (can cause weight gain, lipid abnormalities, and tardive dyskinesia)
and anticonvulsants (also associated with weight gain); rare that someone with bipolar disorder on only one medication
(increases possibility for drug interactions and costs)
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| Bipolar disorder in adults: lifetime prevalence 1% to 4%, median age at onset 21 yr; 50% to 60% of adults with bipolar
disorder report that, in retrospect, onset of mania or depression probably began in childhood
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| Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV): criteria for mood episodes established
only for adults, which may make it difficult for youth to meet criteria; eg, manic episode requires that symptoms be
present for ≥2 wk, but duration may be much shorter in youth; in bipolar I disorder, patient has had one manic or mixed
episode, with or without major depressive episode or depressive symptoms; in bipolar II disorder, patient has had ≥1 major
depressive episode and hypomania; in bipolar disorder not otherwise specified (NOS), patient has manic symptoms
but does not meet criteria for bipolar I or bipolar II
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| Cycling: switching from mania to depression or vice versa; rapid cycling refers specifically to ≥4 episodes per year of
manic, hypomanic, or major depressive episodes; ultra-rapid cycling means cycling occurring on hours-to-days basis; ultradian
cycling occurs on minutes-to-hours basis; latter 2 terms not found in DSM-IV because they occur mostly in children,
and studies confirm that youth generally cycle more rapidly than adults
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| Epidemiology of bipolar disorder in youth: prevalence in general population, 1%; in children seen at psychiatric facilities,
7%; more boys diagnosed than girls, especially in younger age groups; hypothesized that one-third of children with
depression may be experiencing early-onset bipolar disorder
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| Course and Outcome of Bipolar Youth (COBY) study: found that most children with diagnosis of bipolar disorder NOS
met all criteria for bipolar I, except for duration of episodes; 25% to 85% of patients had family history of mental illness
(range varied with specific mental illness); patients themselves had dramatic history of symptoms (including suicidality),
psychiatric hospitalizations, and treatment with medications; symptom history may help in differentiating
bipolar disorder from other childhood psychiatric disorders; eg, children with attention-deficit/hyperactivity disorder
(ADHD) usually not suicidal or hospitalized
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 | Prevalence of comorbid conditions: any anxiety disorder, 37% to 60%; ADHD, 43% to 62%; oppositional defiant disorder,
23% to 41%; conduct disorder, 12% to 13%; substance use disorder, 7% to 10%
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| Prepubertal and early adolescent bipolar disorder: study of 93 children, average age 10.9 yr; 10% had ultrarapid cycling,
77% had ultradian cycling; ADHD comorbidity high
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| Differentiating bipolar disorder from ADHD: both groups report distractibility and hyperenergetic state, but those with
bipolar disorder more frequently exhibit grandiosity, elated mood, daredevil acts, flight of ideas, hypersexuality, and
decreased need for sleep
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| 4-yr follow-up: found these children spend most of their time in some sort of episode, whether treated or not; even when
treated, patients respond for a time, then relapse
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| Screening tools: study that compared 6 screening tools found parents’ reports usually better than children’s or teachers’;
study concluded that Parent General Behavior Inventory or Parent Young Mania Rating Scale most useful tools for differentiating
diagnosis of bipolar disorder; both available from authors at no cost; speaker trying to adapt these assessments
for use in inpatient unit
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| ANXIETY DISORDERS IN YOUTH —Gail A. Bernstein, MD, Endowed Professor in Child and Adolescent Anxiety Disorders,
and Head, Child and Adolescent Anxiety and Mood Disorders Program, Department of Psychiatry, University of
Minnesota Medical School
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| Assessment tools: Anxiety Disorders Interview Schedule for DSM-IV (ADIS); Multidimensional Anxiety Scale for Children
(MASC); Screen for Child Anxiety Related Emotional Disorders (SCARED); clinical interviews with child and parents
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| Comorbidity: common; youth with anxiety disorders tend to have multiple anxiety disorders; in preadolescents, most common
comorbidity after additional anxiety disorder is ADHD (25%); in adolescents, most common comorbidities are depression,
substance use disorder, and bipolar disorder; comorbidity may influence functioning, treatment choice, and
treatment outcome
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| Treatment approaches: cognitive behavioral therapy (CBT); medications, especially selective serotonin reuptake inhibitors
(SSRIs); combination of CBT and medication
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| CBT: manualized therapy (speaker uses as primary psychosocial intervention); components that target anxiety include relaxation
training, cognitive modification (ie, helping children identify anxious thoughts and replace them with healthier
thoughts), behavioral interventions (eg, exposure), and teaching problem-solving techniques
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| When to combine CBT and medications: reserve for children with severe anxiety with functional impairment across several
settings, those with partial response to CBT, those with comorbidity (especially ADHD), and older youths
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| Selective serotonin reuptake inhibitors: first choice for anxiety disorders; 4 randomized clinical trials support use of
SSRIs for anxiety disorders in children, and included participants with separation anxiety disorder (SAD), generalized
anxiety disorder (GAD), and/or social phobia (SP); 60% to 70% had 2 anxiety disorders, and 25% to 30% had 3
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| Studies showed efficacy of: fluvoxamine and fluoxetine for SAD, GAD, and SP; sertraline and paroxetine for GAD;
studies ranged from 8 to 18 wk, and all showed SSRI superior to placebo
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| Another study showed: SSRIs not better than placebo for children with major depressive disorder; some efficacy in adolescents
with major depressive disorder; study concluded that since 30% to 40% of youth with major depressive disorder
have concurrent anxiety disorder, SSRIs may benefit depression by decreasing anxiety
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| Which SSRI is best? no studies directly compare efficacy of SSRIs head-to-head; no scientific evidence to recommend
specific SSRI for particular anxiety disorder or particular patient; in fluvoxamine study, increased severity of symptoms
and social phobia predicted less favorable response to fluvoxamine; in fluoxetine study, increased severity of
symptoms and family history of anxiety predicted less favorable response to fluoxetine
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| Treatment guidelines: choice of SSRI guided by side effect profile, family history of positive response to specific agent,
half-life of drug, and potential drug interactions; start with very low dose and increase gradually, based on side effects
and clinical response; in placebo-controlled trials, benefit apparent by wk 4; no laboratory tests or electrocardiography
necessary for short-term use
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| Side effects: stomachache and motor activation most common in children; motor activation more common in children
with symptoms of ADHD; do not confuse motor activation (common and tends to occur early in treatment) with bipolar
switching (rare and tends to occur later in treatment); bipolar switching involves motor activation but also includes
mood switching (possibly rapid) and problems with impulse control; treat motor activation by decreasing dose or discontinuing
medication; treat bipolar switching by discontinuing medication and adding mood stabilizer if necessary;
bipolar switching in youth who takes antidepressant is pharmacologically induced phenomenon and may or may not
lead to bipolar disorder
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| Drug interactions: fluoxetine and paroxetine inhibit liver enzymes at cytochrome P450 2D6 (CYP2D6), which leads to increased
levels of drugs metabolized at CYP2D6, including tricyclic antidepressants, risperidone, and aripiprazole
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| Other considerations: some youth do not respond to SSRIs; treatment options include longer period of drug treatment,
higher dose of drug, switching to another drug (such as from one SSRI to another), augmenting with another drug (eg,
clomipramine, risperidone, clonazepam, or second SSRI), and combining CBT with medication; duration of
treatment—1 yr after remission of symptoms; taper down during period of low stress (eg, summer vacation); taper SSRIs
with short half-life to avoid withdrawal symptoms; if relapse occurs during taper-down or drug-free period, restart
SSRI
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| Obsessive-compulsive disorder (OCD): considered anxiety disorder, but studied separately from SAD, GAD, and SP;
several studies support efficacy of SSRIs in youth with OCD, but SSRIs usually produce only 30% to 40% reduction in
symptoms and should therefore be combined with CBT; clinical effects of SSRIs may occur within 3 wk, but often require
6 to 12 wk for improvement; average dose usually effective; youth who does not respond to a particular SSRI may
respond to another; after 2 or 3 failed SSRI trials, try clomipramine
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| Pediatric OCD Treatment Study (POTS) recommendations: begin treatment with CBT alone or CBT plus SSRI; most
youth with OCD treated with SSRI, with or without atypical antipsychotic; better dissemination of CBT protocols needed
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| Other medications: benzodiazepines—use rarely and only in combination with SSRI or tricyclic antidepressant while
waiting for response to antidepressant; contraindicated in youth with alcohol or substance use; side effects can be impairing
and include sedation, cognitive problems, disinhibition, and difficulty with discontinuation
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| Anxiety with comorbid ADHD: can be treated with stimulant plus SSRI; monitor side effects that may exacerbate comorbidity
(eg, SSRI causing motor activation or stimulant exacerbating anxiety)
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Suggested Reading
[No authors listed] Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on
Pediatric Psychopharmacology Anxiety Study Group. N Engl J Med 344:1279, 2001; Axelson D et al: Phenomenology of
children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 63:1139, 2006; Birmaher B et al: Fluoxetine
for the treatment of childhood anxiety disorders. J Am Acad Child Adolesc Psychiatry 42:415, 2003; Birmaher B et al:
Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. J
Am Acad Child Adolesc Psychiatry 38:1230, 1999; Chengappa KN et al: Relationship of birth cohort and early age at onset
of illness in a bipolar disorder case registry. Am J Psychiatry 160:1636, 2003; Compton SN et al: Pharmacotherapy for
anxiety disorders in children and adolescents: an evidence-based medicine review. Pediatr Ann 36:586, 2007; Connolly
SD, Bernstein GA: Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents
with anxiety disorders. J Am Acad Child Adolesc Psychiatry 46:267, 2007; Geller B et al: Bipolar disorder at prospective
follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry 158:125, 2001; Geller B et
al: Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar
disorder phenotype. Arch Gen Psychiatry 61:459, 2004; Koran LM et al: American Psychiatric Association. Practice
guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry 164(7 Suppl):5, 2007; Lish JD
et al: The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord
31:281, 1994; Loebel AD et al: Duration of psychosis and outcome in first-episode schizophrenia. Am J Psychiatry
149:1183, 1992; March JS et al: The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability,
and validity. J Am Acad Child Adolesc Psychiatry 36:554, 1997; McClellan J et al: Work Group on Quality Issues. Practice
parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc
Psychiatry 46:107, 2007; Pardo PJ et al: Classification of adolescent psychotic disorders using linear discriminant analysis.
Schizophr Res 87:297, 2006; Rynn MA et al: Placebo-controlled trial of sertraline in the treatment of children with
generalized anxiety disorder. Am J Psychiatry 158:2008, 2001; Schulz SC et al: First-episode psychosis: a clinical approach.
J Am Board Fam Pract 13:430, 2000; Wagner KD et al: A multicenter, randomized, double-blind, placebo-controlled
trial of paroxetine in children and adolescents with social anxiety disorder. Arch Gen Psychiatry 61:1153, 2004;
White T et al: The schizophrenia prodrome. Am J Psychiatry 163:376, 2006; Youngstrom EA et al: Comparing the diagnostic
accuracy of six potential screening instruments for bipolar disorder in youths aged 5 to 17 years. J Am Acad Child
Adolesc Psychiatry 43:847, 2004.
Educational Objectives
| The goal of this program is to improve the diagnosis and treatment of schizophrenia, bipolar disorder, and anxiety disorders
in children and adolescents. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Explain the significance of the early stages of schizophrenia.
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| 2. Differentiate between schizophrenia and bipolar disorder in youth.
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| 3. Initiate appropriate treatment for schizophrenia and bipolar disorder in youth.
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| 4. Discuss family issues associated with schizophrenia, bipolar disorder, and anxiety disorders in youth.
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| 5. Provide effective treatment for anxiety disorders in youth.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and
not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Schulz is a consultant
to Eli Lilly and AstraZeneca, is on the Speakers’ Bureaus for Eli Lilly and AstraZeneca, receives grant/research support
from Eli Lilly, Abbott, and AstraZeneca, and receives honoraria from Eli Lilly and AstraZeneca. Dr. Oberstar is on the
Speakers’ Bureau for AstraZeneca and receives CME-lecture support from Abbott. Dr. Bernstein and the planning committee
reported nothing to disclose. All speakers discussed the off-label use of medications in youth.
Acknowledgements
Drs. Schulz, Oberstar, and Bernstein were recorded at the 8th Annual Psychiatry Review—Youth Mental Health: Bridging
Research and Clinical Practice, held September 17-18, 2007, in Minneapolis, MN, and sponsored by the University of
Minnesota Medical School. The Audio-Digest Foundation thanks the speakers and the University of Minnesota Medical
School for their cooperation in the production of this program.
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