Pediatric Psychopharmacology

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Pediatric Psychopharmacology

• Steven Domon, M.D.
• Laurence Miller, M.D.

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Objectives

• Review medications used in children for
  psychiatric indications
• Discuss levels of evidence for use (off label
  vs. FDA-approved)
• Discuss age-specific issues (comorbidity)
• Discuss psychosocial interventions

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Off label use

• No FDA-approval for a given use
• Very common in pediatrics
• Not unique to psychiatric medications
• Often supported by research or other evidence
• Often represents standard of care

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Stimulants/ADHD Medications

• As a class, stimulants have among the best
  evidence of efficacy of any psychotropic
• All work about equally well
• Superior to other medications used for ADHD
• Strict compliance less important for effect
• Short and long-acting formulations

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Stimulants/ADHD Medications (cont.)

• Side effects weight loss, insomnia,
  irritability, cardiac conduction problems
• Methylphenidate
• Short-acting Ritalin, Methylin, Focalin
• Long-acting Ritalin LA and SR, Metadate ER and
  CD, Focalin XR, Concerta, Daytrana Patch

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Stimulants/ADHD Medications (cont.)

• Amphetamines
• Short-acting Adderall, Dexedrine, Dextrostat,
  Desoxyn
• Long-acting Adderall XR, Dexedrine Spansule,
  Vyvanse

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Stimulants/ADHD Medications (cont.)

• Atomoxetine (Strattera)
• Mechanism similar to antidepressants
• Less effective than stimulants, generally
  considered second-line except in certain cases
• Less abuse potential
• Requires strict compliance to be effective
• May take weeks to reach effect

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Stimulants/ADHD Medications (cont.)

• FDA approved uses
• Adderall and Dexedrine age 3 and up
• Others age 6 and up
• Others
• Bupropion (Wellbutrin)and antidepressant
• Modafanil (Provigil)for narcolepsy
• Clonidine (Catapres)an antihypertensive
• Guanfacine (Tenex)an antihypertensive

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Antihypertensives

• Used to treat impulsivity, irritability,
  disruptive behavior, and aggression
• Alpha agonistsoften used as adjuncts to
  stimulants
• Clonidine
• Guanfacine
• Beta Blockersused more for aggression than as an
  adjunct to stimulants
• Propranolol

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Antidepressants

• Many classes tricyclics, MAOIs, SSRIs, SNRIs,
  others
• Have been used for a variety of disorders other
  than depression
• All work about equally well but individuals may
  respond preferentially
• Warnings of suicide may have been overblown

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Monoamine Oxidase Inhibitors (MAOIs)

• Phenylzine (Nardil), tranylcypromine (Parnate),
  isocarboxazid (Marplan)
• Rarely used in children due to dietary
  restrictions and drug interactions.

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Tricyclic Antidepressants (TCAs)

• With MAOIs, the oldest antidepressants
• Imipramine (Tofranil), desipramine (Norpramin),
  clomipramine (Anafranil), amitriptyline (Elavil),
  nortriptyline (Pamelor), protriptyline
  (Vivactil), others
• Standard of care for years, now second-line (at
  best)

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TCAs (cont.)

• Side effects dry mouth, sedation, constipation,
  blurred vision, cardiac rhythm effects, very
  dangerous in overdose
• FDA-approvals
• Imipramineenuresis age 6 and up
• ClomipramineOCD age 6 and up

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Selective Serotonin Reuptake Inhibitors (SSRIs)

• Fluoxetine (Prozac), sertraline (Zoloft),
  paroxetine (Paxil), citalopram (Celexa),
  escitalopram (Lexapro), fluvoxamine (Luvox)
• Safer and much better tolerated than MAOIs and
  TCAs
• Side effects GI upset, headaches, sexual
  dysfunction, somnolence, insomnia, vivid dreams

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SSRIs (cont.)

• FDA indications
• FluoxetineMDD and OCD age 7 and up
• SertralineOCD age 6 and up
• Paroxetinenone
• Citalopramnone
• Escitalopramnone
• FluvoxamineOCD age 6 and up

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Serotonin-Norepinephrine Reuptake Inhibitors
(SNRIs)

• Venlafaxine (Effexor), duloxetine (Cymbalta),
  trazadone (Desyrel), nefazodone (formerly
  Serzone)
• Similar mechanism to SSRIs
• Nefazodonevery sedating, risk of liver failure
  resulted in decreased use
• FDA approval in children under age 18 none

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Other Antidepressants

• Mirtazipine (Remeron)
• Unique mechanism of action
• Common side effects sedation, weight gain,
  headache, vivid dreams
• No FDA approved pediatric indication
• Bupropion (Wellbutrin)
• Unique mechanism of action
• Common side effects GI upset, may lower seizure
  threshold
• No FDA approved pediatric indication

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Antipsychotics

• Typical haloperidol (Haldol), chlorpromazine
  (Thorazine), pimozide (Orap), trifluoperazine
  (Stelazine), many others
• Atypical risperidone (Risperdal), olanzapine
  (Zyprexa), quetiapine (Seroquel), ziprasidone
  (Geodon), aripiprazole (Abilify), clozapine
  (Clozaril)

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Typical Antipsychotics

• Side effects
• weight gain, sedation, mental slowing,
  extrapyramidal side effects such as tremors and
  Parkinsons-like symptoms, and tardive dyskinesia
  
• FDA-approved pediatric uses
• Haldolpsychosis ages 3-12
• Thorazinesevere behavior problems, psychosis 6
  months-12 yrs
• OrapTourettes Syndrome age 12 and up
• Stelazinepsychosis age 6-12
• Some others are indicated for adolescent
  psychosis

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Atypical Antipsychotics

• Work on different neurotransmitters
• Once believed to be safer than typical
  antipsychotics (not necessarily true)
• May have diminished risk of tardive dyskinesia
  when compared to typical antipsychotics
• Side effects same as for typical
  antipsychotics. Recently there has been increased
  attention given to the risk of various metabolic
  disorders (diabetes, breast milk production)
• Often used to treat aggression and disruptive
  behavior in children and adolescents

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Atypical Antipsychotics (cont.)

• FDA-approved uses
• Risperdal
• age 5-16 irritability associated with autism
• age 10-17 bipolar disorder
• age 13-17 schizophrenia
• Abilify
• age 10-17 acute mania or mixed episodes
• age 13-17 schizophrenia
• Zyprexanone
• Seroquelnone
• Geodonnone
• Clozarilnone rarely used in children due to
  risks of bone marrow suppression

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Anxiolytics/Sedatives

• Benzodiazapines
• Diazepam (Valium), lorazepam (Ativan), alprazolam
  (Xanax), clonazepam (Klonopin), oxazepam (Serax)
• Significant abuse potential, especially among
  shorter-acting medications
• Side effects sedation, disinhibition

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Benzodiazapines

• FDA approval for anxiety in children
• Valium for children 6 months and older
• Ativanfor age 12 and over
• Xanaxnone
• Klonopinfor seizures in infants and older
• Seraxfor age 6 and over

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Antihistamines

• Diphenhydramine (Benadryl), hydroxyzine
  (Vistaril)
• FDA approval
• Benadrylnot FDA-approved for anxiety or sedation
  in children
• Vistarilin children for anxiety
• Side effects sedation, dry moth, blurred vision,
  constipation

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Buspirone (Buspar)

• Mechanism is different than benzodiazepines
• Lower abuse potential
• Side effects insomnia, nervousness,
  gastrointestinal upset
• No FDA approval in children

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Other Sedatives

• Zolpidem (Ambien)
• Not FDA-approved for children
• Eszopiclone (Lunesta)
• Not FDA-approved in children
• Trazadone (Desyrel)
• Antidepressant used sometimes as a sedative
• Not FDA-approved in children

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Mood Stabilizers

• Used chiefly to stabilize mood and to diminish
  aggression
• Lithium, anticonvulsants, and antipsychotics
• Lithium
• oldest mood stabilizer
• FDA approval in mania for age 12 and over

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Anticonvulsants

• Valproate/Valproic acid (Depakote, Depakene)
• FDA approval for seizures down to age 10 and for
  mania in adults
• Increased risk of hepatic failure (especially
  below age 2), pancreatic problems, platelet
  depression, and weight gain
• Lamotrigine (Lamictal)
• FDA approval for seizures for ages 2 and above
  and for Bipolar Disorder in adults
• Stevens-Johnson Syndrome

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Anticonvulsants (cont.)

• Carbemazepine (Tegretol, Carbatrol)
• no FDA approval for Bipolar D/O regardless of age
• much published data on its use as a mood
  stabilizer
• Stevens-Johnson Syndrome
• Topirimate (Topamax)no FDA approval for Bipolar
  D/O regardless of age
• Oxcarbazepine (Trileptal)no FDA approval for
  Bipolar D/O regardless of age
• Gabapentin (Neurontin)no FDA approval for
  Bipolar D/O regardless of age

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Antipsychotics as Mood Stabilizers

• any number of antipsychotics may help stabilize
  mood, although some are specifically indicated
  for mood stabilization
• Risperdalage 10-17 for Bipolar Disorder
• Abilifyage 10-17 for acute mania or mixed states

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Preschoolers

• Very few agents are currently FDA-approved for
  psychiatric use in preschoolers.
• Preschool Psychopharmacology Working Group
  (Gleason, et al., JAACAP, 4612, December 2007)
• Developed algorithms for a variety of disorders
• Emphasized the importance of psychosocial
  interventions before medications are utilized in
  part to better support the development of
  emotional and behavioral self-regulation
• Medication recommendations, when made, are
  secondary to psychosocial interventions

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Adolescents

• Often approached from a treatment standpoint as
  little adults, but it is not that simple.
• Substance abuse often becomes a factor
• May lead to other psychiatric problems
• Other psychiatric problems may lead to substance
  abuse
• Sometimes give away or sell their psychiatric
  medications

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Psychosocial Interventions

• Variety of interventionsindividual, family,
  group, etc.
• Multitude of techniquespsychoeducational,
  supportive, psychodynamic, cognitive, behavioral,
  etc.
• Many techniques are highly therapist dependent
• Not all therapy is equal
• Some geographic areas are often underserved
• Lack of psychosocial intervention availability
  may result in higher rates of medication use