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Copyright © The REACH Institute. All rights reserved.

PediatricPsychopharmacology Overview

of Categories and Agents

http://www.thereachinstitute.org/


Learning Objectives

• To describe general guidelines for the use of psychoactive medications in the pediatric population

• To discuss recommendations for establishing an effective working alliance and “partnering” with families

• To review the basic categories and indications of pediatric psychopharmacology


Urgent Appointment—Alex

• Friday, 4:30 pm appointment • Alex is a 14 y/o boy who was discharged from a

psychiatric hospital 4 weeks ago, now running out of medications (family missed follow-up appointment with psychiatrist)

• Alex’s mother, Janet, reports that Alex has “mood swings” and was discharged after two months with a diagnosis of Bipolar Depression, ADHD, and Aggression

• When you ask about Alex’s medications, Alex’s mother gives you this zip-lock bag


• Methylphenidate (Concerta) 18 mg daily

• Lorazepam (Ativan) 1mg TID

• Risperidone (Risperdal) 2 mg BID

• Valproic Acid (Depakote) 750 mg BID (no level available)

• Escitalopram (Cipralex) 20 mg daily

Urgent Appointment—Alex


Activity: Medication ReconciliationActivity: Medication Reconciliation TABLES – As a group: Identify classes, indications,

and dose levels for each bottle of medication.

SCRIBES: On your flipchart, create a chart with 4 columns:

– Name of agent

– Class (or type) of drug

– Indication: What is it used for?

– Dose: Is the dose low, average, or too high?

Complete the chart for each medication in Alex’s bag.


The REACH First Principles1: Developmental / Contextual Assessment

•Assess children & adolescents’ networks: family, friends, neighborhood, schools, etc.

• Do a thorough diagnostic & bio-psycho-social evaluation

• Medications cannot replace needs for family support, safety, parenting skills, friends, meaningful hobbies, self-esteem, etc.

•Diagnostic systems (DSM & ICD) have limitations in assessing children and their contexts

– Diagnoses may unfold over time, and initial symptoms and diagnoses may differ from later adult diagnoses

•Psychiatric medications are generally just one part of a meaningful, effective treatment plan

Adapted from Connor and Meltzer: Pediatric Psychopharmacology


2: Team Formation, Communication, and Decision-Making• Fully involve family & child in decision-making re:

medications use (shared decision making)– Inquire about concerns, continue to address their concerns

• Medication approaches must recognize chronicity of childhood neuropsychiatric disorders, by providing:– Parental and youth support, empowerment, self-management,

and patient activation to promote recovery and hope– Sustained therapeutic alliance and problem-solving

• Treat primary diagnosis (or the most urgent or impairing problem) with indicated medication first

• Use systematic rating scale to measure agreed-upon target symptoms at baseline and throughout treatment

The REACH First Principles


3: Do No Harm

• Children & youth are different than adults e.g. developmental differences for efficacy & side effects– E.g. SSRIs, TCAs, stimulants

• Children may require proportionately higher doses: faster metabolism, kidney clearance, and liver-to-body-size ratio

• Use medications at appropriate RCT-documented dose and duration before changing or augmenting

• Start low, go slow, taper slow (exception: stimulants can be discontinued more quickly)

• Use systematic rating method to measure side effects

Adapted from Connor and Meltzer: Pediatric Psychopharmacology



4: Evidence-based Prescribing Practices

• Whenever possible, use medications supported by double-blind RCTs for this age group and diagnosis

•Minimize use of multiple medications

•When changing meds:– Make only one med change at a time; monitor results– Always consider environmental strategies as alternative or complement– “Don’t change horses mid-stream”

•Evaluate iatrogenic effects of multiple medications– When unclear, consider tapering or discontinuing most worrisome

medication or the one with the least amount of RCT evidence



RESOURCE SLIDE: Effective Working Alliance

• Ensure case formulation precedes prescription

• Emote a sense of understanding in communications with patients and families

• Involve the patient/family in the decision-making process

• Assess the understanding of the mental illness and meaning of medication for the patient and family

• Nurture all professional relationships necessary to sustain child’s health

• Visit consumer websites often and help families connect to support groups

• Identify references and books to help patients

• When discussing pharmacotherapy, pause and listen to family’s response to word “medication”

• Provide a small number of choice of medications whenever possible so that past associations with a particular med do not derail treatment

• Respect the family’s right to informed consent and need to know about side effects, without burdening them with so much info they feel overwhelmed

• Practice the 3 C’s of good pharmacotherapy:– Collaboration (therapists, other providers,

families)– Conscientiousness (of standard of practice

and socio-cultural needs)– Communication (return phone calls and e-

mails promptly, be available, document so others follow pharmacotherapy reasoning

• Remember all actions have potential meaning for patients and families, from pens, to language, to the way the prescriber provides realistic hope for the future

From Joshi, Teamwork: The Therapeutic Alliance in Pediatric Pharmacotherapy, Child and Adolescent Psych Clinics of NA, Jan 2006See A 1.0


Studies and Acronyms to Know

MTA: Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder

PATS: The Preschool ADHD Treatment Study

TADS: Treatment for Adolescents with Depression Study

CAMS: The Child/Adolescent Multimodal Study


Studies Referenced MTA: Multimodal Treatment Study of Children with

Attention Deficit Hyperactivity Disorder - Examined for the first time the safety and relative effectiveness of these two treatments—alone and in combination for a time period of up to 14 months, and compared these treatments to routine community care. Combination treatment and medication management alone were both significantly superior to intensive behavioral treatment alone and to routine community care in reducing ADHD symptoms. The study also showed that these benefits last for as long as 14 months.

See WBk A 1.6


PATS: The Preschool ADHD Treatment Study provides us with the best information to date about treating very young children diagnosed with ADHD," said NIMH Director Thomas R. Insel, MD. "The results show that preschoolers may benefit from low doses of medication when it is closely monitored, but the positive effects are less evident and side-effects are somewhat greater than previous reports in older children."

Studies Referenced

See WBk A 1.7


Studies Referenced

TADS: Treatment for Adolescents with Depression Study - A multi-site clinical research study examining the short- and long-term effectiveness of an antidepressant medication and psychotherapy alone and in combination for treating depression in adolescents ages 12 to 17.

See WBk A 1.8


Studies Referenced

CAMS: The Child/Adolescent Multimodal Study randomly assigned 488 children and adolescents ages 7 to 17 years to one of four treatment options for a 12 week period. 81 percent of children and adolescents receiving combination treatment improved. Sixty percent of them receiving CBT only improved and 55 percent receiving antidepressant medication only improved. Twenty four percent of those receiving only placebo improved.

See WBk A 1.9


What medications are used for ADHD?

Copyright © 2014 The REACH Institute. All rights reserved.


FDA-Approved Medications for ADHD

• Stimulants• Methylphenidate – e.g., Ritalin (LA), Concerta, Focalin

(XR), Daytrana, Methylin, Metadate (CD), Quillivant XR

• Amphetamine – e.g., Dexedrine, Adderall (XR), Vyvanse

• Non-stimulants• Atomoxetine (Strattera)

• Guanfacine XR (Intuniv)

• Clonidine XR (Kapvay)


Stimulant Medications: Efficacy

• Safety and efficacy studies in over 200 controlled studies of ADHD in school-age children

• One of the most robust treatments in psychiatry

• Effective in approximately 70% of children with ADHD—generally equal efficacy across stimulants

• An additional 20% will respond to the next one attempted

• If the 1st and 2nd choices fail, check for wrong diagnosis and/or previously unrecognized comorbidity


Stimulant Medications: Mechanisms

Receptors

Synapse

DopamineNorepinephrine

NerveImpulse

DAT Transporter

MPHblocks

TH

• MPH exerts much of its effect through dopamine uptake blockade by inhibition of dopamine transporter (DAT) of central adrenergic neurons

• By contrast, amphetamines not only block DAT, but also increase catecholamine release as a primary mechanism

• Both increase spontaneously released dopamine that enhances response to environmental stimuli


Non-Stimulant Medication Efficacy

Non-Stimulant Medication Efficacy

Atomoxetine (Strattera) is approved for the treatment of children, adolescents, and adults with ADHD– Head-to-head comparison with OROS-methylphenidate

(Concerta): OROS-MPH more effective than atomoxetine (Newcorn et al, Am J Psychiatry, 2008), e.g. Effect sizes 0.8-1.0 vs. 0.4-0.5 in stimulant naive

Guanfacine XR (Intuniv) and Clonidine XR (Kapvay) approved for the treatment of children & adolescents 6-17


Non-Stimulant Medication Mechanism of Action

Non-Stimulant Medication Mechanism of Action

Atomoxetine (Strattera) blocks reuptake at the noradrenergic neurons (selective noradrergic reuptake inhibition – SNRI)

Guanfacine XR (Intuniv) and Clonidine XR (Kapvay) - alpha-2A adrenergic receptor agonists


Cardiovascular Monitoring and Stimulants

A thorough patient and family history and physical examination should be performed.

Treatment without obtaining routine ECGs or routine subspecialty cardiology evaluations is appropriate for most children.

Acquiring an ECG is not mandatory, but rather is left to the physician's discretion.

PEDIATRICS Volume 122, Number 2, August 2008

*More to come in ADHD Unit


What about theantidepressant medications?



Treatments for Depression• Pharmacotherapy

• Fluoxetine (Prozac)--FDA approved for pediatric patients 8-18 years of age

• Escitalopram (Lexapro)--FDA approved for adolescents 12-17 years of age

• Psychotherapy: Cognitive Behavioral Therapy (CBT)

• Interpersonal psychotherapy- some evidence supporting role in pediatric depression

• ECT

• Light Therapy

• TMS (transcranial magnetic stimulation) – preliminary study


Antidepressants—Mechanism

• SSRIs selectively block the reuptake of 5-HT (first-line pharmacotherapy)

• TCAs block the reuptake of 5-HT and/or norepinephrine

• MAOIs block monoamine oxidase (MAO), thereby blocking metabolism and increasing neurotransmitter availability in the synapse


MEDICATION Drug Placebo P value

Fluoxetine (Prozac) (March ’04)* 56% 33% 0.02

Fluoxetine (Prozac) (Emslie ’97) 52% 37% 0.03

Fluoxetine (Prozac) (Emslie ’02) 61% 35% 0.001

Paroxetine (Paxil) (Keller ’01)** 66% 48% 0.02

Paroxetine (Paxil) (Unpublished) 69% 57% NS

Paroxetine (Paxil) (Unpublished) 65% 46% 0.005

Citalopram (Celexa) (Wagner ’04) 47% 45% NS

Sertraline (Zoloft) (Wagner ’03) 63% 53% 0.05

Escitalopram (Cipralex) (Emslie ’09) 64% 53% 0.03

*Fluoxetine alone compared to placebo**Paroxetine compared to placebo

Response Rates in RCT’s of Antidepressants (for depression) based on CGI (Clinical Global Impression)


The FDA Boxed Warning“the Black Box”

• Suicidality– incr. risk of suicidality in children, adolescents and young adults w/ major

depressive or other psychiatric disorders esp. during 1st months of tx w/ antidepressants vs. placebo; weigh risk vs. benefit; in short-term studies of antidepressants vs. placebo, suicidality risk not increased in pts >24 y/o, and risk decreased in pts >65 y/o; observe all pts for clinical worsening, suicidality, or unusual behavior changes

• Applies to all medications with FDA indication for depression

– Antidepressants (SSRIs, SNRIs, TCAs, MAOIs, others)

– Others with FDA indication For example, quetiapine (Seroquel) has the warning due to indication in adults

for bipolar depression and aripiprazole (Abilify) has the warning due to indication in adults for adjunct treatment of depression

• To be discussed further in upcoming sessions


What aboutmood stabilizers and

antipsychotics forchildren and adolescents?



Mood Stabilizers• Lithium—only traditional mood stabilizer with

FDA indication for treatment of Bipolar Disorder in children 12 and older

• Valproic Acid—FDA indication for seizure disorder in children (but not for Bipolar Disorder)

• Carbamazepine (Tegretol)—FDA indication for seizure disorder (but not for Bipolar Disorder)

• Oxcarbazepine (Trileptal)—evidence stronger for younger children (no FDA indication for Bipolar Disorder)


Atypical Antipsychotics• Risperidone (Risperdal)

– FDA indication for bipolar disorder, Acute Mania for children 10-17 – Also has indication for schizophrenia for children ages 13-17 and the

irritability symptoms of autistic disorder in children ages 5-16

• Aripiprazole (Abilify)– FDA indication for bipolar disorder, Acute Mania for children 10-17 – Also has indication for schizophrenia for children ages 13-17 and the

irritability symptoms of autistic disorder in children ages 6-17

• Quetiapine (Seroquel)– FDA indication for bipolar disorder, Acute Mania for children 10-17– Also has indication for schizophrenia for children ages 13-17

• Olanzapine (Zyprexa)– FDA indication for bipolar disorder, manic or mixed episodes , ages 13-17– Also has indication for schizophrenia for children ages 13-17

• Evidence also for aggression but must weigh side effects and consider general principles (thorough diagnostic eval, treat primary disorder, etc)


Adapted from: Pappadopulos EA et al. Schizophr Bull. 2002;28:111-121. Marder et al, 2003; Potkin et al, 2003.

SEE T-MAY Reference Guide

Antichol-inergic

Elevated prolactin EPS

Ortho-stasis

QTcIncrease Sedation

Weight Gain

Clozapine ++++ 0/+ 0/+ +++ + ++++ ++++

Risperidone + ++++ ++ ++ + + +++

Olanzapine ++ ++ + ++ + +++ ++++

Quetiapine + 0/+ 0/+ ++ + ++ ++

Ziprasidone + + + + ++ + 0/+

Aripiprazole* 0/+ 0/+ + + 0 + 0/+

Safety and Tolerability ofAtypical Antipsychotics


Monitoring Side Effects

• Antipsychotic Use in Children and Adolescents: Minimizing Adverse Effects to Maximize Outcomes. – Correll, C. Journal of the American Academy

of Child & Adolescent Psychiatry. 47(1):9-20, January 2008

• BMI Percentile Calculator– http://apps.nccd.cdc.gov/dnpabmi/Calculator.a

spx, T-MAY Tool Kit

http://apps.nccd.cdc.gov/dnpabmi/Calculator.aspx

http://apps.nccd.cdc.gov/dnpabmi/Calculator.aspx


Summary• Meds in Pediatric Psychopharmacology

have extensive data in support of safety and efficacy, given the correct diagnosis

• The most common disorders (ADHD, depression, anxiety, and disruptive behavior disorders) can be effectively treated & monitored in primary care – you can do it!

• Many children will benefit by your learning the safe & appropriate use of these agents


REMINDER: Please fill out Unit A

evaluation


RESOURCE SLIDE:Annotated Bibliography

• Pediatric Psychopharmacology: Fast Facts.– Book by Daniel Connor and Bruce Meltzer reviewing psychiatric medications

for children and adolescents by medication and by disorder. Information is clearly and effectively organized and communicated. Latest version: 2006

• Straight Talk About Psychiatric Medications for Kids– Book and guide for parents (and prescribers) by Timothy Wilens about

medications for kids. Addresses questions such as: When is medication the right choice? What are the alternatives? Are medications safe for my growing child?

• The Prescriber’s Guide– Reference book by Stephen Stahl providing easy-to-understand graphics for

all psychiatric medications. Not focused on children and adolescents.

See WBk A 1.4


RESOURCE SLIDE: Additional Resources forPrimary Care Clinicians

• www.pdr.net– This web site is free for US-based prescribers. It offers

access to the PDR entries for medications which are updated on a regular basis

• www.epocrates.com– Free on-line version allows access to latest data on

medications, including dosing for FDA indications. Palm/Pocket version also available

• www.parentsmedguide.org– This web site is a collaborative effort by the American

Academy of child and Adolescent Psychiatry and the American Psychiatric Association. Practical information and advice for parents, patients and clinicians is posted regarding ADHD, pediatric depression and bipolar disorder.

See WBk A 1.5

copyright © the reach institute. all rights reserved. pediatric psychopharmacology overview of...

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