Pediatric Pediatric PsychopharmacolPsychopharmacol

ogyogySteven Domon, M.D.Steven Domon, M.D.

Laurence Miller, M.D.Laurence Miller, M.D.

ObjectivesObjectives

Review medications used in children Review medications used in children for psychiatric indicationsfor psychiatric indications

Discuss levels of evidence for use Discuss levels of evidence for use (“off label vs. FDA-approved)(“off label vs. FDA-approved)

Discuss age-specific issues Discuss age-specific issues (comorbidity)(comorbidity)

Discuss psychosocial interventionsDiscuss psychosocial interventions

““Off label use”Off label use”

No FDA-approval for a given useNo FDA-approval for a given use Very common in pediatricsVery common in pediatrics Not unique to psychiatric Not unique to psychiatric

medicationsmedications Often supported by research or Often supported by research or

other evidenceother evidence Often represents “standard of care”Often represents “standard of care”

Stimulants/ADHD Stimulants/ADHD MedicationsMedications

As a class, stimulants have among the As a class, stimulants have among the best evidence of efficacy of any best evidence of efficacy of any psychotropicpsychotropic

All work about equally wellAll work about equally well Superior to other medications used Superior to other medications used

for ADHDfor ADHD Strict compliance less important for Strict compliance less important for

effecteffect Short and long-acting formulationsShort and long-acting formulations

Stimulants/ADHD Stimulants/ADHD Medications (cont.)Medications (cont.)

Side effects: weight loss, insomnia, Side effects: weight loss, insomnia, irritability, cardiac conduction irritability, cardiac conduction problemsproblems

MethylphenidateMethylphenidate Short-acting: Short-acting: Ritalin, Methylin, FocalinRitalin, Methylin, Focalin Long-acting: Long-acting: Ritalin LA and SR, Ritalin LA and SR,

Metadate ER and CD, Focalin XR, Metadate ER and CD, Focalin XR, Concerta, Daytrana PatchConcerta, Daytrana Patch

Stimulants/ADHD Stimulants/ADHD Medications (cont.)Medications (cont.)

AmphetaminesAmphetamines Short-acting: Short-acting: Adderall, Dexedrine, Adderall, Dexedrine,

Dextrostat, DesoxynDextrostat, Desoxyn Long-acting: Long-acting: Adderall XR, Dexedrine Adderall XR, Dexedrine

Spansule, VyvanseSpansule, Vyvanse

Stimulants/ADHD Stimulants/ADHD Medications (cont.)Medications (cont.)

Atomoxetine (Atomoxetine (StratteraStrattera):): Mechanism similar to antidepressantsMechanism similar to antidepressants Less effective than stimulants, generally Less effective than stimulants, generally

considered second-line except in certain considered second-line except in certain casescases

Less abuse potentialLess abuse potential Requires strict compliance to be Requires strict compliance to be

effectiveeffective May take weeks to reach effectMay take weeks to reach effect

Stimulants/ADHD Stimulants/ADHD Medications (cont.)Medications (cont.)

FDA approved uses:FDA approved uses: AdderallAdderall and and DexedrineDexedrine age 3 and up age 3 and up Others age 6 and upOthers age 6 and up

Others:Others: Bupropion (Bupropion (WellbutrinWellbutrin)—and antidepressant)—and antidepressant Modafanil (Modafanil (ProvigilProvigil)—for narcolepsy)—for narcolepsy Clonidine (Clonidine (CatapresCatapres)—an antihypertensive)—an antihypertensive Guanfacine (Guanfacine (TenexTenex)—an antihypertensive)—an antihypertensive

AntihypertensivesAntihypertensives Used to treat impulsivity, irritability, Used to treat impulsivity, irritability,

disruptive behavior, and aggressiondisruptive behavior, and aggression Alpha agonists—often used as adjuncts to Alpha agonists—often used as adjuncts to

stimulants:stimulants: ClonidineClonidine GuanfacineGuanfacine

Beta Blockers—used more for aggression Beta Blockers—used more for aggression than as an adjunct to stimulants:than as an adjunct to stimulants: PropranololPropranolol

AntidepressantsAntidepressants

Many classes: tricyclics, MAOIs, Many classes: tricyclics, MAOIs, SSRIs, SNRIs, othersSSRIs, SNRIs, others

Have been used for a variety of Have been used for a variety of disorders other than depressiondisorders other than depression

All work about equally well but All work about equally well but individuals may respond individuals may respond preferentiallypreferentially

Warnings of suicide may have been Warnings of suicide may have been overblownoverblown

Monoamine Oxidase Monoamine Oxidase Inhibitors (MAOIs)Inhibitors (MAOIs)

Phenylzine (Phenylzine (NardilNardil), tranylcypromine ), tranylcypromine ((ParnateParnate), isocarboxazid (), isocarboxazid (MarplanMarplan))

Rarely used in children due to Rarely used in children due to dietary restrictions and drug dietary restrictions and drug interactions.interactions.

Tricyclic Antidepressants Tricyclic Antidepressants (TCAs)(TCAs)

With MAOIs, the oldest With MAOIs, the oldest antidepressantsantidepressants

Imipramine (Imipramine (TofranilTofranil), desipramine ), desipramine ((NorpraminNorpramin), clomipramine ), clomipramine ((AnafranilAnafranil), amitriptyline (), amitriptyline (ElavilElavil), ), nortriptyline (nortriptyline (PamelorPamelor), protriptyline ), protriptyline ((VivactilVivactil), others ), others

Standard of care for years, now Standard of care for years, now second-line (at best)second-line (at best)

TCAs (cont.)TCAs (cont.)

Side effects: dry mouth, sedation, Side effects: dry mouth, sedation, constipation, blurred vision, cardiac constipation, blurred vision, cardiac rhythm effects, rhythm effects, very dangerous in very dangerous in overdoseoverdose

FDA-approvals:FDA-approvals: Imipramine—enuresis age 6 and upImipramine—enuresis age 6 and up Clomipramine—OCD age 6 and upClomipramine—OCD age 6 and up

Selective Serotonin Selective Serotonin Reuptake Inhibitors Reuptake Inhibitors

(SSRIs)(SSRIs) Fluoxetine (Fluoxetine (ProzacProzac), sertraline (), sertraline (ZoloftZoloft), ),

paroxetine (paroxetine (PaxilPaxil), citalopram (), citalopram (CelexaCelexa), ), escitalopram (escitalopram (LexaproLexapro), fluvoxamine ), fluvoxamine ((LuvoxLuvox) )

Safer and much better tolerated than Safer and much better tolerated than MAOIs and TCAsMAOIs and TCAs

Side effects: GI upset, headaches, sexual Side effects: GI upset, headaches, sexual dysfunction, somnolence, insomnia, vivid dysfunction, somnolence, insomnia, vivid dreams dreams

SSRI’s (cont.)SSRI’s (cont.)

FDA indications:FDA indications: Fluoxetine—MDD and OCD age 7 and Fluoxetine—MDD and OCD age 7 and

upup Sertraline—OCD age 6 and upSertraline—OCD age 6 and up Paroxetine—none Paroxetine—none Citalopram—none Citalopram—none Escitalopram—none Escitalopram—none Fluvoxamine—OCD age 6 and up Fluvoxamine—OCD age 6 and up

Serotonin-Serotonin-Norepinephrine Norepinephrine

Reuptake Inhibitors Reuptake Inhibitors (SNRIs) (SNRIs) Venlafaxine (Venlafaxine (EffexorEffexor), duloxetine ), duloxetine

((CymbaltaCymbalta), trazadone (Desyrel), ), trazadone (Desyrel), nefazodone (formerly nefazodone (formerly SerzoneSerzone) )

Similar mechanism to SSRIs Similar mechanism to SSRIs Nefazodone—very sedating, risk of Nefazodone—very sedating, risk of

liver failure resulted in decreased useliver failure resulted in decreased use FDA approval in children under age FDA approval in children under age

18: none18: none

Other AntidepressantsOther Antidepressants Mirtazipine (Mirtazipine (RemeronRemeron):):

Unique mechanism of actionUnique mechanism of action Common side effects: sedation, weight gain, Common side effects: sedation, weight gain,

headache, vivid dreamsheadache, vivid dreams No FDA approved pediatric indicationNo FDA approved pediatric indication

Bupropion (Bupropion (WellbutrinWellbutrin):): Unique mechanism of actionUnique mechanism of action Common side effects: GI upset, may lower Common side effects: GI upset, may lower

seizure thresholdseizure threshold No FDA approved pediatric indication No FDA approved pediatric indication

AntipsychoticsAntipsychotics

Typical: haloperidol (Typical: haloperidol (HaldolHaldol), ), chlorpromazine (chlorpromazine (ThorazineThorazine), pimozide ), pimozide ((OrapOrap), trifluoperazine (), trifluoperazine (StelazineStelazine), many ), many others others

Atypical: risperidone (Atypical: risperidone (RisperdalRisperdal), ), olanzapine (olanzapine (ZyprexaZyprexa), quetiapine ), quetiapine ((SeroquelSeroquel), ziprasidone (), ziprasidone (GeodonGeodon), ), aripiprazole (aripiprazole (AbilifyAbilify), clozapine ), clozapine (Clozaril)(Clozaril)

Typical AntipsychoticsTypical Antipsychotics Side effects:Side effects:

weight gain, sedation, mental slowing, extrapyramidal weight gain, sedation, mental slowing, extrapyramidal side effects such as tremors and Parkinson’s-like side effects such as tremors and Parkinson’s-like symptoms, and tardive dyskinesia symptoms, and tardive dyskinesia

FDA-approved pediatric usesFDA-approved pediatric uses HaldolHaldol—psychosis ages 3-12—psychosis ages 3-12 ThorazineThorazine—severe behavior problems, psychosis 6 —severe behavior problems, psychosis 6

months-12 yrsmonths-12 yrs OrapOrap—Tourette’s Syndrome age 12 and up—Tourette’s Syndrome age 12 and up StelazineStelazine—psychosis age 6-12—psychosis age 6-12 Some others are indicated for adolescent psychosis Some others are indicated for adolescent psychosis

Atypical AntipsychoticsAtypical Antipsychotics Work Work on different neurotransmitterson different neurotransmitters Once believed to be safer than typical Once believed to be safer than typical

antipsychotics (not necessarily true)antipsychotics (not necessarily true) May have diminished risk of tardive dyskinesia May have diminished risk of tardive dyskinesia

when compared to “typical” antipsychoticswhen compared to “typical” antipsychotics Side effects: same as for “typical” antipsychotics. Side effects: same as for “typical” antipsychotics.

Recently there has been increased attention Recently there has been increased attention given to the risk of various metabolic disorders given to the risk of various metabolic disorders (diabetes, breast milk production)(diabetes, breast milk production)

Often used to treat aggression and disruptive Often used to treat aggression and disruptive behavior in children and adolescentsbehavior in children and adolescents

Atypical Antipsychotics Atypical Antipsychotics (cont.)(cont.)

FDA-approved uses:FDA-approved uses: RisperdalRisperdal

age 5-16 irritability associated with autismage 5-16 irritability associated with autism age 10-17 bipolar disorderage 10-17 bipolar disorder age 13-17 schizophreniaage 13-17 schizophrenia

AbilifyAbilify age 10-17 acute mania or mixed episodesage 10-17 acute mania or mixed episodes age 13-17 schizophreniaage 13-17 schizophrenia

ZyprexaZyprexa—none —none SeroquelSeroquel—none —none GeodonGeodon—none—none ClozarilClozaril—none; rarely used in children due to risks —none; rarely used in children due to risks

of bone marrow suppressionof bone marrow suppression

Anxiolytics/SedativesAnxiolytics/Sedatives

BenzodiazapinesBenzodiazapines Diazepam (Diazepam (ValiumValium), lorazepam (), lorazepam (AtivanAtivan), ),

alprazolam (alprazolam (XanaxXanax), clonazepam ), clonazepam ((KlonopinKlonopin), oxazepam (), oxazepam (SeraxSerax))

Significant abuse potential, especially Significant abuse potential, especially among shorter-acting medicationsamong shorter-acting medications

Side effects: sedation, disinhibitionSide effects: sedation, disinhibition

BenzodiazapinesBenzodiazapines

FDA approval for anxiety in children:FDA approval for anxiety in children: ValiumValium— for children 6 months and — for children 6 months and

olderolder AtivanAtivan—for age 12 and over—for age 12 and over XanaxXanax—none—none KlonopinKlonopin—for seizures in infants and —for seizures in infants and

olderolder SeraxSerax—for age 6 and over —for age 6 and over

AntihistaminesAntihistamines Diphenhydramine (Diphenhydramine (BenadrylBenadryl), hydroxyzine ), hydroxyzine

((VistarilVistaril))

FDA approval:FDA approval: BenadrylBenadryl—not FDA-approved for anxiety or —not FDA-approved for anxiety or

sedation in childrensedation in children VistarilVistaril—in children for anxiety—in children for anxiety

Side effects: sedation, dry moth, blurred Side effects: sedation, dry moth, blurred vision, constipation vision, constipation

Buspirone Buspirone (Buspar)(Buspar)

Mechanism is different than Mechanism is different than benzodiazepinesbenzodiazepines

Lower abuse potentialLower abuse potential

Side effects: insomnia, nervousness, Side effects: insomnia, nervousness, gastrointestinal upsetgastrointestinal upset

No FDA approval in children No FDA approval in children

Other SedativesOther Sedatives

Zolpidem Zolpidem (Ambien)(Ambien) Not FDA-approved for childrenNot FDA-approved for children

Eszopiclone Eszopiclone (Lunesta)(Lunesta) Not FDA-approved in childrenNot FDA-approved in children

Trazadone (Trazadone (Desyrel)Desyrel) Antidepressant used sometimes as a Antidepressant used sometimes as a

sedativesedative Not FDA-approved in childrenNot FDA-approved in children

Mood StabilizersMood Stabilizers

Used chiefly to stabilize mood and to Used chiefly to stabilize mood and to diminish aggression diminish aggression

Lithium, anticonvulsants, and Lithium, anticonvulsants, and antipsychoticsantipsychotics

Lithium:Lithium: oldest mood stabilizeroldest mood stabilizer FDA approval in mania for age 12 and over FDA approval in mania for age 12 and over

AnticonvulsantsAnticonvulsants Valproate/Valproic acid (Valproate/Valproic acid (Depakote, Depakote,

DepakeneDepakene)) FDA approval for seizures down to age 10 and FDA approval for seizures down to age 10 and

for mania in adultsfor mania in adults Increased risk of hepatic failure (especially Increased risk of hepatic failure (especially

below age 2), pancreatic problems, platelet below age 2), pancreatic problems, platelet depression, and weight gaindepression, and weight gain

Lamotrigine (Lamotrigine (LamictalLamictal)) FDA approval for seizures for ages 2 and FDA approval for seizures for ages 2 and

above and for Bipolar Disorder in adultsabove and for Bipolar Disorder in adults Stevens-Johnson Syndrome Stevens-Johnson Syndrome

Anticonvulsants (cont.)Anticonvulsants (cont.) Carbemazepine (Carbemazepine (Tegretol, CarbatrolTegretol, Carbatrol))

no FDA approval for Bipolar D/O regardless of no FDA approval for Bipolar D/O regardless of ageage

much published data on it’s use as a mood much published data on it’s use as a mood stabilizerstabilizer

Stevens-Johnson SyndromeStevens-Johnson Syndrome Topirimate (Topirimate (TopamaxTopamax)—no FDA approval for )—no FDA approval for

Bipolar D/O regardless of ageBipolar D/O regardless of age Oxcarbazepine (Oxcarbazepine (TrileptalTrileptal)—no FDA approval for )—no FDA approval for

Bipolar D/O regardless of ageBipolar D/O regardless of age Gabapentin (Gabapentin (NeurontinNeurontin)—no FDA approval for )—no FDA approval for

Bipolar D/O regardless of ageBipolar D/O regardless of age

Antipsychotics as Mood Antipsychotics as Mood StabilizersStabilizers

any number of antipsychotics may any number of antipsychotics may help stabilize mood, although some help stabilize mood, although some are specifically indicated for mood are specifically indicated for mood stabilizationstabilization

RisperdalRisperdal—age 10-17 for Bipolar —age 10-17 for Bipolar DisorderDisorder

AbilifyAbilify—age 10-17 for acute mania or —age 10-17 for acute mania or mixed states mixed states

PreschoolersPreschoolers Very few agents are currently FDA-approved Very few agents are currently FDA-approved

for psychiatric use in preschoolers. for psychiatric use in preschoolers. Preschool Psychopharmacology Working Preschool Psychopharmacology Working

Group (Gleason, et al., Group (Gleason, et al., JAACAPJAACAP, 46:12, , 46:12, December 2007)December 2007) Developed algorithms for a variety of disordersDeveloped algorithms for a variety of disorders Emphasized the importance of psychosocial Emphasized the importance of psychosocial

interventions before medications are utilized in interventions before medications are utilized in part to better support the development of part to better support the development of emotional and behavioral self-regulationemotional and behavioral self-regulation

Medication recommendations, when made, are Medication recommendations, when made, are secondary to psychosocial interventions secondary to psychosocial interventions

AdolescentsAdolescents

Often approached from a treatment Often approached from a treatment standpoint as “little adults,” but it is not standpoint as “little adults,” but it is not that simple.that simple.

Substance abuse often becomes a Substance abuse often becomes a factorfactor May lead to other psychiatric problemsMay lead to other psychiatric problems Other psychiatric problems may lead to Other psychiatric problems may lead to

substance abusesubstance abuse Sometimes give away or sell their Sometimes give away or sell their

psychiatric medicationspsychiatric medications

Psychosocial Psychosocial InterventionsInterventions

Variety of interventions—individual, family, Variety of interventions—individual, family, group, etc.group, etc.

Multitude of techniques—psychoeducational, Multitude of techniques—psychoeducational, supportive, psychodynamic, cognitive, supportive, psychodynamic, cognitive, behavioral, etc.behavioral, etc.

Many techniques are highly therapist Many techniques are highly therapist dependentdependent

Not all “therapy” is equalNot all “therapy” is equal Some geographic areas are often underservedSome geographic areas are often underserved Lack of psychosocial intervention availability Lack of psychosocial intervention availability

may result in higher rates of medication usemay result in higher rates of medication use