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Pediatric Psychopharmacology

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

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  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): • Unique mechanism of action • Common side effects: GI upset, may lower seizure threshold • No FDA approved pediatric indication

  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 10-17 bipolar disorder • age 13-17 schizophrenia • Abilify • age 10-17 acute mania or mixed episodes • age 13-17 schizophrenia • 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) • 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

  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 10-17 for Bipolar Disorder • Abilify—age 10-17 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

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