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

“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”

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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)

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

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

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 Zyprexa—none Seroquel—none Geodon—none Clozaril—none; rarely used in children due to risks of bone marrow suppression

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

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

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

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

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

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

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

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

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

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

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

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