1. Pediatric Psychopharmacology
Steven Domon, M.D.
Laurence Miller, M.D.

2. 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

3. “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”

4. 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

5. 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

6. Stimulants/ADHD Medications (cont.)
Amphetamines
Short-acting: Adderall, Dexedrine, Dextrostat, Desoxyn
Long-acting: Adderall XR, Dexedrine Spansule, Vyvanse

7. 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

8. 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

9. Antihypertensives
Used to treat impulsivity, irritability, disruptive behavior, and aggression
Alpha agonists—often used as adjuncts to stimulants:
Clonidine
Guanfacine
Beta Blockers—used more for aggression than as an adjunct to stimulants:
Propranolol

10. 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

11. Monoamine Oxidase Inhibitors (MAOIs)
Phenylzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan)
Rarely used in children due to dietary restrictions and drug interactions.

12. 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)

13. TCAs (cont.)
Side effects: dry mouth, sedation, constipation, blurred vision, cardiac rhythm effects, very dangerous in overdose
FDA-approvals:
Imipramine—enuresis age 6 and up
Clomipramine—OCD age 6 and up

14. 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

15. SSRI’s (cont.) FDA indications: Fluoxetine—MDD and OCD age 7 and up
Sertraline—OCD age 6 and up
Paroxetine—none
Citalopram—none
Escitalopram—none
Fluvoxamine—OCD age 6 and up

16. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Venlafaxine (Effexor), duloxetine (Cymbalta), trazadone (Desyrel), nefazodone (formerly Serzone)
Similar mechanism to SSRIs
Nefazodone—very sedating, risk of liver failure resulted in decreased use
FDA approval in children under age 18: none

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

18. 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)

19. Typical Antipsychotics
Side effects:
weight gain, sedation, mental slowing, extrapyramidal side effects such as tremors and Parkinson’s-like symptoms, and tardive dyskinesia
FDA-approved pediatric uses
Haldol—psychosis ages 3-12
Thorazine—severe behavior problems, psychosis 6 months-12 yrs
Orap—Tourette’s Syndrome age 12 and up
Stelazine—psychosis age 6-12
Some others are indicated for adolescent psychosis

20. 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

21. Atypical Antipsychotics (cont.)
FDA-approved uses:
Risperdal
age 5-16 irritability associated with autism
age bipolar disorder
age schizophrenia
Abilify
age acute mania or mixed episodes
Zyprexa—none
Seroquel—none
Geodon—none
Clozaril—none; rarely used in children due to risks of bone marrow suppression

22. 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

23. Benzodiazapines FDA approval for anxiety in children:
Valium— for children 6 months and older
Ativan—for age 12 and over
Xanax—none
Klonopin—for seizures in infants and older
Serax—for age 6 and over

24. Antihistamines Diphenhydramine (Benadryl), hydroxyzine (Vistaril)
FDA approval:
Benadryl—not FDA-approved for anxiety or sedation in children
Vistaril—in children for anxiety
Side effects: sedation, dry moth, blurred vision, constipation

25. Buspirone (Buspar) Mechanism is different than benzodiazepines
Lower abuse potential
Side effects: insomnia, nervousness, gastrointestinal upset
No FDA approval in children

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

27. 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

28. 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

29. Anticonvulsants (cont.)
Carbemazepine (Tegretol, Carbatrol)
no FDA approval for Bipolar D/O regardless of age
much published data on it’s 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

30. Antipsychotics as Mood Stabilizers
any number of antipsychotics may help stabilize mood, although some are specifically indicated for mood stabilization
Risperdal—age for Bipolar Disorder
Abilify—age for acute mania or mixed states

31. Preschoolers
Very few agents are currently FDA-approved for psychiatric use in preschoolers.
Preschool Psychopharmacology Working Group (Gleason, et al., JAACAP, 46:12, 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

32. 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

33. Psychosocial Interventions
Variety of interventions—individual, family, group, etc.
Multitude of techniques—psychoeducational, 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