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Psychotropic meds for kids and adolescents: WHATS NEW


Symptoms, incidence, prognosis, non- medication treatments, etc. ... controlled trial (Konijnenberg et al. , 2006) showed no benefit of Lexapro vs. ... – PowerPoint PPT presentation

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Title: Psychotropic meds for kids and adolescents: WHATS NEW

Psychotropic medsfor kids and adolescentsWHAT
  • Mark D. Edelstein, MD
  • Child Adolescent Psychiatrist
  • EMQ Children and Family Services
  • Victor Community Support Services
  • CMHACY - May, 2007

What we will cover
  • Meds in kids Dos Donts
  • FDA Approval and Off-Label Use
  • Evidence Based Practice
  • Foster children foster youth
  • Psychiatric Disorders Evidence-based prescribing
    Whats New

What we will not cover
  • Details about medicines
  • How they work, doses, side
  • effects, etc.
  • Details about disorders
  • Symptoms, incidence, prognosis, non- medication
    treatments, etc.
  • Evidence for benefit of med in adults

Some Dos Donts
  • Fewest number lowest doses that work.
  • Good evaluation.
  • Discuss findings. Diagnosis is not everything.
  • Weigh risks and benefits using meds but also of
    not using meds.
  • One part of the plan. Never meds only.

Some Dos Donts
  • Discuss med options.
  • Dose Start low, go slow, but get to effective
    dose (kids metabolize meds faster).
  • Monitor target symptoms watch for side effects.
    Try to resolve problems (to a point).
  • When possible, make one change at a time.
  • Consider causes of ineffectiveness wrong med,
    not enough time, dose too low (or high), not
    taking it, med wears off, tolerance, or not a
    med-responsive symptom.

  • Pharmaceutical companies research potential
  • After preclinical testing come 3 phases of
    clinical trials in humans) each must be approved
    by the FDA.
  • FDA approves a medicine to be advertised as safe
    and effective for specific medical conditions
    within a specific age group

Off-Label Prescribing
  • Once approved, doctor can prescribe any dose to
    any person for any reason.
  • Off-label prescribing prescribing outside age
    parameters diagnosis

Off-Label Prescribing
  • Pharmaceutical companies done little research on
    meds in kids (except for stimulants)
  • Disorders in the real world are not as clear-cut
    as in most research samples
  • additional research and clinical experience may
    show safety and efficacy in different populations
    and for different disorders.

Evidence Based Practice
  • Medicine a long history of EBP, but greater
    emphasis on it since 1990s.
  • Research type quality vary
  • Best research prospective, randomized,
    placebo-controlled, double-blind
  • Rely on research in kids, research in adults,
    clinical experience (e.g., case reports)

Evidence Based Practice
  • Efficacy (efficacious)
  • Works in controlled setting
  • Effectiveness (effective)
  • Works in the real world

Foster Children Youth
  • As with all kids
  • Informed consent by adult.
  • Developmentally appropriate informed assent by
    the child or youth.

Foster Children Youth
  • Logistical challenges of Court authorization.
  • Foster youth sensitive to being involved and
    listened to.
  • Public policy influenced by concern but also
  • Lack of knowledge
  • Lack of data
  • Irrational fears
  • Poor prescribing practices
  • May not appreciate risks of not treating

  • First line option for ADHD
  • 3 types
  • Methylphenidate (Ritalin, Ritalin-LA, Concerta,
    Metadate, Methylin, etc.)
  • Dexmethylphenidate (Focalin, Focalin-XR)
  • Amphetamine salts (Adderall, Adderall-XR)
  • FDA-approved (MPH to 6, Adderall to 3)
  • Efficacy well established 70 have significant
    response (resolved in fewer)

Stimulants Whats New
  • Sudden death? In 2006 FDA review found no
    evidence of increased risk except with structural
    cardiac abnormality.
  • Use in preschoolers? Effective but
    hyperactivity, impulsivity and inattention may
    not represent ADHD, and preschoolers may be more
    prone to growth impairment.
  • Increasing treatment of ADHD in adults
    (Focalin-XR, Adderall-XR Strattera also
    FDA-approved in adults)

Stimulants Whats New
  • Dexmethylphenidate (Focalin, Focalin-XR) the
    d-enantiomer of Methylphenidate
  • Methylphenidate Transdermal System Daytrana
    patch lasts 9 hours (if leave on)
  • Lisdexamfetamine dimesylate (Vyvnase)
    FDA-approved dextroamphetamine linked to lysine
    inactive if snorted or injected

Atomoxetine (Strattera)
  • Norepinephrine Reuptake Inhibitor
  • FDA-approved in children (6 and older),
    adolescents adults.
  • 5 randomized controlled trials show efficacy in
    children and adolescents.
  • Head-to-head studies favor stimulants.
  • Takes weeks to start working.
  • Long-lasting and non-abusable.

Other meds for ADHD
  • Not FDA-approved for ADHD less evidence
  • Bupropion (Wellbutrin-SR, Wellbutrin-XL)
  • Guanfacine (Tenex) Clonidine (Catapres)
  • Some studies show benefit
  • Expect approval for XR form of Guanfacine.
  • Modafinil (Provigil for narcolepsy)
  • Multi-center 2006 study showed efficacy but
    potential for skin reaction needs more study.
  • Tricyclic antidepressants

Bipolar Disorder
  • 3 categories of mood stabilizers
  • Lithium
  • Anticonvulsants (valproic acid/divalproex
    oxcarbazepine, lamotrigine, et al.)
  • Atypical antipsychotics (risperidone, olanzapine,
    quetiapine, et al.)
  • Very few rigorous studies in pediatric
    population, especially for bipolar depression
    maintenance therapy.

Acute mania Mixed Episodes
  • Efficacious in children adolescents
  • Lithium (most studied)
  • Probably efficacious
  • Divalproex (Depakote)
  • Lamotrigine (Lamictal)
  • Atypical antipsychotics
  • Inconclusive, no or negative evidence
  • Carbamazepine (Tegretol), oxcarbazepine
    (Trileptal), topiramate (Topamax), gabapentin

More on Bipolar Disorder
  • About 50 of pediatric patients Bipolar Disorder
    fail to respond to monotherapy.
  • One controlled trial showed Depakote Quetiapine
    superior to Depakote placebo in adolescents.
  • Open trials suggest efficacy of Lithium combined
    with an antipsychotic or anticonvulsant.

Bipolar Depression Maintenance
  • Bipolar Depression
  • No good evidence
  • Lithium, Lamictal, SSRIs may help
  • Maintenance
  • No good evidence
  • In 2005 a panel of experts from the Child
    Adolescent Bipolar Foundation recommended
    continuing same meds that worked acutely for
    12-24 months.

Depression Children
  • High placebo response makes research difficult
    (also true in adolescents).
  • No solid evidence of benefit from antidepressants
    for depression.
  • Compared to adolescents, children have 3 times
    rate of activation/agitation from SSRIs.
  • Omega-3 fatty acids appear safe but mixed
    results in adults one small, controlled
    double-blind study in children suggested benefit
    (Nemets et al., 2006)

Depression TADS
  • TADS Treatment for Adolescents with Depression
    Study (Data collected 2000-2003)
  • Randomized, double blind multi-center study of
    439 adolescents with Major Depressive Disorder
  • Improvement rates
  • Fluoxetine CBT 71
  • Fluoxetine alone 60
  • CBT alone 43 - not statistically
    significant vs. placebo
  • Placebo 35
  • Even in combined group, only 37 remission.

Depression SSRIs in Adolescents
  • Fluoxetine (Prozac) the only FDA-approved
    antidepressant for depression in adolescents
  • Do other SSRIs work?
  • Paxil shown in 4 studies to be no more effective
    than placebo in adolescent MDD except perhaps
    helpful in older adolescents.
  • Multi-center placebo-controlled trial
    (Konijnenberg et al. , 2006) showed no benefit of
    Lexapro vs. placebo for 6-11 year olds but
    significant improvement in global functioning in
    12-17 year olds.

Other Antidepressants in Adolescents
  • Bupropion (Wellbutrin-SR, Wellbutrin-XL)
    probably 2nd line agent (after SSRIs)
  • Venlafaxine (Effexor-XR) open label trial in
    showed effectiveness (but activating withdrawal
  • Others TCAs, mirtazepine (Remeron), lithium
    augmentation (inhibitors
  • Omega-3 fatty acids appear safe but mixed
    results in adults promising small controlled
    double-blind study in children (Nemets et al.,

Do Antidepressants Increase Suicide Risk?
  • 2004 FDA meta-analysis confirmed controversial
    British 2003 meta-analysis of increased
    suicidality (4 vs. 2 with placebo) except
  • No completed suicides in the studies
  • 2004 Black Box Warning recommendation for
    follow-up visits weekly x 4, every other week x
    2, and at 12 weeks.
  • Concern about risk of depressed adolescents not
    getting treatment.

Do Antidepressants Increase Suicide Risk?
  • 2004 placebo-controlled study by Eli Lilly (maker
    of Prozac) suicidality and self-harm in
    pediatric population same for fluoxetine
  • 2004 Valuck et al. review of over 24,000
    adolescents treated with antidepressants for MDD
    suggested antidepressants did not contribute to
    increased risk in suicide.
  • 2004 FDA reassessment of its data paroxetine
    venlafaxine linked with increased suicidality but
    others showed little or no effect.

Do Antidepressants Increase Suicide Risk?
  • 11/06 FDA reviewed 372 randomized
    placebo-controlled trials involving almost
    100,000 adults.
  • Risk of suicidality clearly age-related
  • 65 and over striking and statistically
    significant protective effect
  • 31-64 modest protective effective
  • 25-30 neutral effective on suicidal thoughts and
  • 19-24 increased risk of suicidal thoughts and
    behavior, though not statistically significant.

TADS revisited
  • Adolescents felt to be dangerous to themselves
    were excluded from the study.
  • Still, 29 had suicidal ideation at the start and
    21 had some form of suicidal behavior.
  • This decreased substantially over 12 weeks for
    all treatment groups (less than 10 had suicidal
    ideation after 12 weeks) but decreased most in
    the fluoxetine CBT group.
  • 18 incidents of new or worsening suicidal
    ideation and 5 of suicidal behavior (no completed
    suicides) most occurred over a month after
    initiating treatment.
  • Risk of suicidal behavior did not differ among
  • Risk of suicidal ideation higher (3.7) in the
    fluoxetine-only and placebo groups (CBT
    protective?) but not statistically significant.

Do Antidepressants Increase Suicide Risk?
  • 2006 Simon et al. reviewed 5000 treatment
  • episodes of pediatric patients with

Do Antidepressants ReduceSuicide Risk?
  • From 2003 to 2004
  • 20 decline in antidepressant prescriptions
    written for youth under age 20
  • 18 increase in suicides in this age
  • Gibbons et al.(2006) from 1996-98, areas of the
    country that had highest rate of SSRI
    prescriptions had lowest rates of suicide rates
    in children and young adolescents
  • May be very important to distinguish between
    suicidal ideation and suicidal behavior (duh)

Antidepressants Suicide Risk
  • Possible increased risk of suicidal ideation
    (and behavior?) in young people from
    (particular?) antidepressants (therapy
  • Probable reduction in suicides with effective
  • treatment (best medicine therapy)
  • Solution for MDD in adolescents (as in any
    similar situation in the medical field)
  • Diagnose and Treat
  • Educate and Monitor

  • Antipsychotics efficacious in adults evidence
    less but still good in pediatric population
  • Atypical (2nd generation) antipsychotics
  • Risperidone (Risperdal)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Clozapine (Clozaril)
  • Aripiprazole (Abilify)
  • Ziprasidone (Geodon)
  • Also used as mood stabilizers, for agitation
    aggression, and tics

CATIE (Phase I)
  • About the same somewhat effectiveness
  • Olanzapine a little more efficacious but also
    more side effects. Ziprasidone the opposite.
    Risperdal good balance.
  • High rates of discontinuation of all meds
  • Due to inefficacy or side effects.
  • Perphenazine as effective as the atypicals
  • No greater incidence of EPS.

1st vs. 2nd Generation
  • May see increased use of 1st generation meds
  • Perphenazine (Trilafon), Haloperidol (Haldol),
    Chlorpromazine (Thorazine), etc.
  • Why?
  • Less cost
  • Concerns about Metabolic Syndrome with atypicals
    (next slide)
  • A problem?
  • CATIE is one study
  • Greater risk of certain side effects (tardive
    dyskinesia, NMS, others?)

Metabolic Syndrome
  • Combination of increased
  • Waist circumference
  • Blood pressure
  • Blood sugar
  • Triglycerides and lipids
  • High cardiovascular risk (heart attack, stroke)
  • Greatest risk from Clozaril Olanzapine
  • Moderate risk from Risperdal Seroquel
  • Minimal to no risk from Abilify Geodon.
  • Family history monitoring

Forms of Atypical Antipsychotics
Paliperidone (Invega)
  • Brand new from Janssen
  • The main active metabolite of risperidone
  • Risperdal is off-patent
  • Slow release (OROS) system once daily dosing
  • FDA approved for adults with schizophrenia

  • Clearly established in adults as the most
    efficacious antipsychotic (and effective mood
    stabilizer), though with significant side
  • Studies now suggest this also applies to children
    and adolescents.
  • Shaw et al. (2006) in children adolescents
    with onset of schizophrenia before age 13,
    clozapine worked faster and better than
    Olanzapine also caused more side effects.

  • As of 8/05, no double-blind randomized placebo-
    controlled trials of meds for PTSD in children.
  • CBT most important treatment.
  • Hyperarousal may be best target symptom for meds
    (vs. re-experience avoidance/numbing)
  • 1st line SSRIs (some SSRIs have FDA approval
    for PTSD in adults). Favorable response reported
    in children and adolescents.
  • Other options buspirone cyproheptadine or
    trazodone for insomnia clonidine, guanfacine
  • Less evidence for benzodiazepines, TCAs,
    bupropion, antipsychotics, anticonvulsants

Other Anxiety Disorders
  • OCD, Separation Anxiety, GAD, Social Anxiety
  • CBT most important treatment
  • For OCD, Fluvoxamine, Zoloft, and Clomipramine
    are FDA-approved in pediatric patients (probably
    all SSRIs can be helpful)

Affective/Impulsive Aggression
  • Seen in some Oppositional Defiant Disorder, etc.
  • 2006 meta-analysis of suggests improvement in
    pediatric population with Lithium, typical
    antipsychotics, Risperdal, and possibly others.
  • Mixed results for valproic acid.

  • Risperdal FDA-approved in 2006 for aggression,
    self-injury, tantrums, and mood lability in
    children (age 5-16) with autistic disorders.
  • 2005 review of studies reported moderate benefit
    for Risperdal and Olanzapine.
  • No effect on core symptoms of autism.

Eating Disorders
  • Anorexia nervosa
  • No meds indicated except cautious treatment of
    co-occurring MDD or OCD
  • Bulimia
  • CBT is first line treatment
  • SSRIs clearly can be effective
  • Fluoxetine is FDA-approved for adults

Alcohol Opioid Dependence
  • Little to no research in adolescents
  • Alcohol dependence in adults
  • Naltrexone acamprosate each increase duration
    of abstinence in about 15 of individuals.
  • Opioid dependence in adults
  • Methadone significantly reduces amount of opioid
  • Naltrexolne decreases craving and blocks the
    high from opioids