Pediatric psychopharmacology

Introduction
In general, there is a paucity of research in the field of pediatric psychopharmacology. Many practices are considered “off-label,” meaning there is no FDA approval. This is also true of many non-psychiatric medications and their uses in children (perhaps half or more medication interventions in children are “off-label”). This does not mean that such practices are not supported by some level of evidence (sometimes a large volume of published evidence), and such practices may be consistent with the standard of care. Many practices in children are “extensions” of practices in adults, although dosing in children may be different due to metabolic and/or developmental differences. *In the context of this presentation, references to FDA approval are included for informational purposes and not as an endorsement or criticism of treatment practices. Classes of Medications
*Please note that the following is not intended to serve as an exhaustive listing of all psychopharmacologic agents used in children nor does it necessarily reflect my practices. More detailed information regarding the mechanisms of these medications is beyond the scope of this presentation. This section is instead intended to address, in a general manner, many of the more common agents used in children and adolescents. Agents listed are included based on their frequency of use and from questions I have previously received regarding specific medications or prescription practices. Stimulants/ADHD Medications
o The most research evidence for any class of psychopharmacologic agents used in o All work equally well, although individuals may respond differentially o May work well when taken regardless of overall compliance o Short-acting and long-acting formulations o May require multiple daily doses to achieve desired effect o Risks: weight loss, insomnia, irritability, cardiac problems o Methylphenidate  Short-acting forms (Ritalin, Methylin, Focalin)  Long-acting forms (Ritalin LA and SR, Metadate ER and CD, Methylin ER, Focalin XR, Concerta, Daytrana patch)  Short-acting forms (Adderall, Dexedrine, Dextrostat, Desoxyn)  Long-acting forms (Adderall XR, Dexedrine Spansule, Vyvanse)  Adderall (short acting) and Dexedrine age 3 and up  All others age 6 and up o Mechanism more like an antidepressant than a stimulant o Generally considered second-line, after stimulants, except in cases where there is a history of substance abuse or significant anxiety o FDA approval age 6 and up o Advantages:  Lower abuse potential  Longer-lasting effects  Less effective than stimulants  May take weeks to exert effect  Requires strict compliance  Same “Black Box” warning as antidepressants • Other agents sometimes used for ADHD:  Bupropion (Wellbutrin)—an antidepressant (not FDA-approved)  Modafanil (Provigil)—used for narcolepsy—mechanism similar to  Clonidine (Catapres)—an antihypertensive (not FDA-approved)  Guanfacine (Tenex, Intuniv)—an antihypertensive (FDA-approval for Antihypertensives
• Used to treat aggression and disruptive behavior (including hyperactivity and impulsivity, sometimes with ADHD) as well as insomnia and tics (no FDA approval for these uses)  Clonidine and Guanfacine  Usually used as an adjunct to stimulants  While clonidine has been reported to possibly be associated with sudden death when used with methylphenidate, a controlled study showed no cardiac toxicity Antidepressants
• There are many classes of antidepressants, and most are used in children to some extent • As a class, they have been used to treat depression, anxiety disorders, enuresis, symptoms of ADHD, and aggression (among other diagnoses) • All work about equally well for depression in adults, although individuals may respond • The FDA warnings of increased suicide risk (but no increase in completed suicides) resulted in a decrease in prescription rates—and a subsequent increase in completed suicide rates • Monoamine Oxidase Inhibitors (MAOIs) o Phenelzine (Nardil), tranylcypromine (Parnate), and isocarboxazid (Marplan) o Dietary restrictions (cheese, etc.) and interactions with other antidepressants limit o Imipramine (Tofranil), desipramine (Norpramin), clomipramine (Anafranil), amitriptyline (Elavil), nortriptyline (Pamelor), protriptyline (Vivactil), others o Along with MAOIs, among the oldest antidepressants o Standard of care for many years o Common side effects: dry mouth, constipation, urinary retention, memory disturbance, blurred vision, cardiac rhythm disturbances o Cardiac risks/toxicity, risk in overdose, and other side effects have resulted in less o FDA approval in children under age 18:  Imipramine—enuresis age 6 and up  Clomipramine—OCD age 6 and up • Selective Serotonin Reuptake Inhibitors (SSRIs) o Fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox) o In general, safer and better tolerated than TCAs and MAOIs o Common side effects: GI upset, headaches, sexual dysfunction, somnolence, o FDA approval in children under age 18:  Fluoxetine—MDD and OCD age 7 and up  Sertraline—OCD age 6 and up  Paroxetine—none  Citalopram—none  Escitalopram—MDD age 12-17  Fluvoxamine—OCD age 6 and up • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) o Venlafaxine (Effexor), duloxetine (Cymbalta), nefazodone (formerly Serzone) o Similar mechanism to SSRIs o Serzone pulled from market (risk of liver failure) but generic nefazodone is still o Common side effects: as with SSRIs (nefazodone is fairly sedating) o FDA approval in children under age 18: o Common side effects: sedation, weight gain, headache, vivid dreams o No FDA approved pediatric indication o Unique mechanism of action o Common side effects: GI upset, may lower seizure threshold o No FDA approved pediatric indication Antipsychotics
• Typical antipsychotics include haloperidol (Haldol), chlorpromazine (Thorazine), pimozide (Orap), trifluoperazine (Stelazine), many others o Side effects include weight gain, sedation, mental slowing, extrapyramidal side effects” such as tremors and Parkinson’s-like symptoms, and tardive dyskinesia o FDA approval for typical antipsychotics:  Haldol—psychosis ages 3-12  Thorazine—severe behavior problems, psychosis 6 months-12 years  Orap—Tourette’s Syndrome age 12 and up  Stelazine—psychosis age 6-12  Some others are indicated for adolescent psychosis • Atypical antipsychotics include risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), paliperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), clozapine (Clozaril) o Work on different neurotransmitters o Once believed to be safer than typical antipsychotics o May have diminished risk of tardive dyskinesia when compared to “typical” o Risk of various metabolic disorders (diabetes, breast milk production) o Often used to treat aggression and disruptive behavior in children and adolescents o FDA approvals for atypical antipsychotics: • age 5-16 irritability associated with autism • age 10-17 bipolar disorder • age 13-17 schizophrenia • Age 6-17 irritability associated with autism • age 10-17 acute mania or mixed episodes • age 13-17 acute mania or mixed episodes  Geodon—none; currently trying to get FDA-approval for bipolar disorder  Invega—none  Fanapt—none  Saphris—none  Clozaril—none; rarely used in children due to risks of bone marrow Anxiolytics/sedatives
o Diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax), clonazepam (Klonopin), oxazepam (Serax) o Significant abuse potential, especially among shorter-acting medications o Side effects: sedation, disinhibition o 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 o Diphenhydramine (Benadryl), hydroxyzine (Vistaril) o FDA approval:  Benadryl—not FDA-approved for anxiety or sedation in children  Vistaril—in children for anxiety o Side effects: sedation, dry moth, blurred vision, constipation o Mechanism is different than benzodiazepines o Lower abuse potential o Side effects: insomnia, nervousness, gastrointestinal upset o No FDA approval in children Mood Stabilizers
• Used chiefly to stabilize mood and to diminish aggression o oldest mood stabilizer o FDA approval in mania for age 12 and over o 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  FDA approval for seizures for ages 2 and above and for Bipolar Disorder o Carbemazapine (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 o Oxcarbazepine (Trileptal)—no FDA approval for Bipolar D/O regardless of age o Gabapentin (Neurontin)—no FDA approval for Bipolar D/O regardless of age o Topirimate (Topamax)—no FDA approval for Bipolar D/O regardless of age • Antipsychotics—any number of antipsychotics may help stabilize mood, although some are specifically indicated for mood stabilization o Risperdal—age 10-17 for Bipolar Disorder o Abilify—age 10-17 for acute mania or mixed states Preschool Children
• Very few agents are currently FDA-approved for psychiatric use in preschoolers. • Preschool Psychopharmacology Working Group (Gleason, et al., JAACAP, 46:12, o Developed algorithms for a variety of disorders o Emphasized the importance of psychosocial interventions before medications are utilized in part to better support the development of emotional and behavioral self-regulation o Medication recommendations, when made, are secondary to psychosocial

Source: http://www.midsouth.ualr.edu/abuse-neg-conf/2010accanconference/handouts/Domon-Psychiatric%20Medication%20Use.pdf