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Pediatric�Psychopharmacology�
UpdateLaura Shapiro PMHNP-BC, MS, M.Ed, NCSN
Pharmacology Basics⦿ Studies with children are limited⦿ Off label use is common⦿ Almost all meds lower Sz threshold
• *exceptions● Benzo’s● Antiepileptic's
⦿ Children metabolize differently• Size-MG/kg• Growth may increase CYP450 metabolism/inhibition- may
require higher dosing than adults-very individualized● Moving Targets
CYP 450 Hepatic Metabolism⦿ System of enzymes in the liver which
metabolizes compounds such as medications⦿ Many psyche meds inhibit of induce the
enzymes in this system. ⦿ This effects drugs levels in the body
• Especially when medications compete for the same enzyme system
• Most Common Source of drug/drug Interactions ● *OCP’s
CYP 450 med interactions⦿ http://ars.els-cdn.com/content/image/1-s2.0-S1470204510701054-gr1.jpg
SSRI�Selective Serotonin Re-Uptake Inhibitors
Ist line of treatment for tx of depression/anxiety
⦿ TAD study 2006⦿ Depression⦿ Initially combination
therapy + medication modestly favorable
⦿ On repeat virtually no difference between combination therapy and medication alone
⦿ (pt’s in combined tx more likely to dc SSRI)
Frequently prescribed SSRI⦿ Approved⦿ Fluoxetine (Prozac)
• MDD 8years• OCD 7 years• Commonly used off-label
younger/anxiety⦿ More of a response
compared to placebo⦿ Long half life
• Ideal for erratic adolescent administration
⦿ Escitalprolam (Lexapro)• MDD over age 12• 10mg=40mg Citalopram
⦿ Sertraline (Zoloft)• OCD 6 years
⦿ Fluvoxamine(Luvox)• OCD 7 years
SSRI cont’d Paxotene(Paxil )
• More withdrawal side effects
• More sexual side effects• Sometimes used for
premature ejaculation• Sometimes written for
adolescents
⦿ Citalopram (Celexa)• Well tolerated• Cardiac effects● women
Quick and Dirty Neuro Bio SSRI
SSRI Effectiveness⦿ 40-70% of depressed patients treated have a
modest-moderate positive response.⦿ Placebo response rate 30-60%⦿ Medication with CBT reduces relapse rate.
Side Effects of SSRICOMMON RARE
⦿ Often Dose Dependent⦿ Head Aches⦿ GI⦿ Serotonin receptors in gut⦿ Activation of undiagnosed
Bipolar• Sleep Issues• Activation• Sometimes used diagnostically
⦿ Serotonergic Syndrome• Hyperthermia• Agitation• Confusion
⦿ Increase in bleeding time⦿ Nosebleeds/bruising
SSRI and Suicidality⦿ Black box warning⦿ Patients under 25⦿ 11 times more likely to have a + response than
to feel ++ suicidality⦿ Still legally/ethically need to explain risks ⦿ When first initiating tx or increasing dose
• ? Reduces inhibitions/increase in motivation
Student Management on SSRI⦿ No labs routinely drawn⦿ Withdrawal Effects-agitation, somatization⦿ Meds have long half life's-take on average 4 weeks
of a therapeutic dose for any + effect⦿ Ask about medications when you hear head/GI
complaints⦿ Headache and GI upset commonly pass after 2
weeks• Med still not titrated to effectiveness at this point
SSNI-Selective Serotonin Noreperinepherine Re-Uptake Inhibitors
⦿ Often 2nd line in adolescents/Adults⦿ Primary symptom:
• Anhedonia-low motivation⦿ Stahl⦿ Serotonin deficiency vs. Noradrenergic
deficiency
Types of SSNI-seen in child/adolescents⦿ Venlafaxine (Effexor)
• +effect on depressed adolescents
• No efficacy on children pre-puberty
In high doses also block Dopamine uptake
Headaches/nausea reduced in extended release version
Bupropion (Wellbutrin)*NDRI
• Inconclusive data on efficacy
• Wt. loss• Lowers Sz threshold• Not given in females with
hx of eating disorder-Bulimia
TTT
⦿ Mirtazapine-MDD in adolescents off label⦿ Sometimes used in children over 10⦿ Often used as an augmenting agent when there
is a partial response to another med⦿ Sedation ⦿ Weight gain is common
• Blocks histamine receptors
Other Antidepressant meds seen in pedi psyche
⦿ Dysarel (Trazadone)⦿ SARI
• Blocks the transporter⦿ Used for sleep in
<100mg⦿ Priapism serious SE/
more commonly seen in adolescent males
⦿ QT prolongation
⦿ Imipramine (Tofranil)⦿ TCA
• Blocks 5HT/Norepi reuptake.
• Increases Dopa transmission in frontal cortex
⦿ Enuresis-6 years⦿ MDD-off label 12years
Other Antidepressants⦿ Amitriptyline (Elavil)
• Used with caution in adolescents over 12• Migraines• The PCP’s TCA• Sedating
Anxiety⦿ Commonly seen in pediatrics⦿ Trick is determining normal development from
pathology⦿ Types:
• Separation Anxiety• Generalized Anxiety Disorder• Social Phobia• PTSD• Agoraphobia//School Phobia• OCD• Panic
Anxiety: The Benzo’s⦿ AACAP position⦿ “benefit in adult trials but
not in children”⦿ “clinically they are used as
an adjunct short term tx to achieve rapid reduction in severe symptoms”
⦿ May permit the exposure phase of CBT-(the gold standard)
⦿ “Should be used cautiously”⦿ Contraindicated in
adolescents with substance abuse
The Benzo’s⦿ Alprazolam/Xanex⦿ $$$$$$
• Rapid onset• Short half life• QID
⦿ Clonazepam/Klonopin• Longer half life• BID-TID
⦿ Lorazepam/Ativan• Sedation• May be used for sleep• PTSD
⦿ The research:⦿ Simon (1992)
• Avoidant disorder• Perseveration• Alprazolam=PLC
⦿ Graae (1994)• Clonazepam (.5mg-2mg)• Separation Anxiety• Clonazepam=PLC
Bernstein (1990)• School Refusal• Alprazolam (.75-4mg) = PLC
Anxiety: Buspirone⦿ Buspirone/Buspar⦿ Enhance serotonin activity
and contribute to antidepressant actions
⦿ Pregnancy B/animal studies⦿ Main Side Effect
• Dizziness• Activation
⦿ Off label in kids⦿ Commonly prescribed due
to safety profile⦿ 2-4weeks for therapeutic
effect.⦿ Competes with CYP450
3A4 • When used with some
SSRI*Luvox* may require lower dose
• Induced by Tegretol, dose may need to be raised
PTSD: Special Situations⦿ Catapress/Clonodine⦿ Used in children over 6⦿ Off label⦿ Sedating⦿ Monitor BP
• Rebound HTN with rapid d/c
⦿ Aids in Sleep⦿ Decreases activationAlso used as adjunct with
mood stabilizers.
OCD⦿ Approved⦿ Fluvoxamine/Luvox
• Ages 8-17• Above 50mg divide dosing• Steady State
⦿ Sertraline/Zoloft• Age 6-12 initial 25mg/day• >12 adult dosing
⦿ Clomipramine/Anafranil• For children over 10• Sudden death has occurred
in kids• Careful dose titration• 3mg/kg/day
Antipsychotics⦿ 1st generation
• Haloperidol/Haldol● Approved>age 3● Tourette's, agitation, psychosis● EPS-● Anticholinergic,● Akithisia● TD
⦿ Second line after atypical
Atypical Antipsychotics(AAAs)⦿ 2nd Generation⦿ Less uncomfortable SE
than 1st generation
⦿ Commonly prescribed for psychosis in adults
⦿ More commonly prescribed for aggression in children than psychosis
Most Common AAA’s⦿ Clozapine/Clozaril⦿ Risperidone/Risperdal⦿ Olanzapine/Zyprexa⦿ Quetiapine/Seroquel⦿ Ziprasidone/Geodon⦿ Aripiprazole/Abilify⦿ Paliperidone/Invega⦿ Asenapine/SAPHRIS
FDA Approvals⦿ Adolescent Schizophrenia (ages 13-17)⦿ Youth Bipolar I mixed/manic state ⦿ (ages 10-17)
RisperidoneOlanzapineQuetiapineAripiprazole
⦿ Autistic Disorders (irritability)• Resperidone (5-16 years)• Aripiprazole (6-17 years)
AAA General Info⦿ Work by blocking the D2 receptors in the
postsynaptic neuron
⦿ Individual drugs vary by the way the bind to block the receptor
⦿ Prescribing steadily increasing with the pediatric population
⦿ Prescribed more frequently to males, to those in foster care, and those on Medicare• Rogers Procedure
Rogers Procedure⦿ Child in DCF custody with existing or new antipsychotic prescription
⦿ Court appoints Rogers GAL and schedules Rogers hearing
⦿ GAL conducts an investigation, meets with child, psychiatrist and other stake holders.
⦿ GAL submits report to the court
⦿ MD writes affidavit regarding the tx, submits to court
⦿ Court reviews these reports and affidavit and hears statements or objections from child or parents.
⦿ Judge will approve or deny prescription
⦿ Judge will again review Rogers order at a later predetermined time.
Clozapine/Clozaril 1989 ⦿ “800 pound gorilla”⦿ Severe agranulocytosis⦿ National registry⦿ Pharmacy parameters
⦿ 2 Board Certified Psychiatrists sign off for initial prescription
⦿ Off label use in youth with tx refractory schizophrenia • have experienced severe EPS with other
agents
• Research● Greater efficacy than Haldol
for both positive and negative symptoms of schizophrenia
Risperidone/Risperdal⦿ Most studied
• Youth with “disruptive behavior”• Co-Morbid ADHD/sub average IQ• Risperdal > PLC• Some research states may worsen OCD symptoms-not
replicated yet• Long Action Consta injections• Studied in children for long term safety for several different
dx● Aggression/Autism● Increases prolactin● Mod wt gain● Mod EPS Akithsia
Olanzapine/Zyprexa⦿ Well studied⦿ Has shown some efficacy with youth bipolar 1⦿ Weight gainàLipids, Diabetes
• Risk benefit ratio⦿ Injected forms not studied in children⦿ Pedi-need close monitoring⦿ Symbax not yet approved in pedi
• Olanzapine/Fluoxetine combo-Bipolar
Quetiapine/Seroquel⦿ Research:⦿ Approved for:⦿ Schizophrenia ages 13-17 years⦿ Bipolar ages 10-17⦿ Many off label uses
• When combined with Depakote improved adolescent mania greater than PLC• Sedating/Mod wt gain• Potential Benefit:● Aggression● Conduct disorder● Tic Disorders● (AACAP, 2010)
Ziprasidone/Geodon⦿ Off label⦿ The Research:⦿ Low dose may be effective in ages 7-17 with
tic disorder⦿ Low to modest efficacy in youth with bipolar 1⦿ Low weight gain/metabolic effects⦿ Higher incidence of QT prolongation
Aripiprazole/Abilify⦿ Uses:
• Mania• Aggression• PDD/Autism• Adolescent Schizophrenia• In smaller doses used as an adjunct with SSRI for tx
resistant depression• Can be activation/take in morning.• Higher Akathisia● Oral disintegrating tablet, liquid, IM available
Newer MedsInvega (Paliperidone)-Active metabolite of Resperidone
Approved for 12 and older, initially thought to have less side effects but case reports have rapidly increased.
Fanapt (Illoperidone)-Latuda (Lurasidone)Adults with schizophrenia
Saphris (Asenapine)- Approved for bipolar in ages 10-17 & adults and schizophrenia in adults. Requires sublingual delivery.Bad tasting. Avoid food or drink 10 minutes after taking. Any meal with in 4 hours reduces bioavailability by 20%. Drug Interactions inhibits CYP2D6, causing increase in serum levels of drugs metabolized by this enzyme-SSRI’s like Paxil.
Metabolic Syndrome⦿ Weight Changes
• Greater in young people than adults⦿ Diabetes
• Black box warning⦿ Hyperlipidemia
• Alteration is triglycerides correlates with weight gain
ADA Screening guidelines for patients on AAA
⦿ Personal & Family History• Baseline and annually
⦿ Weight• Baseline, 4 weeks, 8 weeks, 12 weeks
⦿ Waist Circumference• Baseline, annually
⦿ Blood Pressure• Baseline 12 weeks, annually
⦿ Fasting Blood Glucose• Baseline, 12 weeks annually
⦿ Fasting Lipids (HDL,LDL,TG, Total Cholesterol)• Baseline, 12 weeks
Cardiovascular SE⦿ The research:
• Cardiac side effects more common in youth than adults per case report.
• Ziprasidone● Baseline EKG?● QT interval prolongation● Torsade's de pointes
• Orthostatic hypotension● Clozapine
• Tachycardia
Agranulocytosis Neutropenia⦿ Clozapine
• Risperidone• Olanzapine• Quetiapine
⦿ Risk greater in children⦿ Potentially Fatal
Hepatic Dysfunction⦿ In youth related to rapid weight gain
• Steatohepatitis• Rare
Prolactin⦿ Dopamine inhibits prolactin⦿ Inhibiting Dopamine disinhibits prolactin⦿ Risperidone
• Amenorrhea• Galactorrhea• Gynecomastia
Neuroleptic Malignant Syndrome (NMS)
⦿ Very rare⦿ Very serious⦿ Autonomic instability
• Elevated temp• Rigidity• Elevated CPK
⦿ Reported in all AAA’s
Other Rare SE⦿ Seizures
• Clozapine⦿ Movement Disorders
• EPS• Withdrawal Dyskinesia's• TD• Low but occurs more often in youth
School Nurse Implications⦿ Assessment⦿ Ask the question!
Mood Stabilizers⦿ Lithium
• Approved in kids > 12 years for Mania/ Mood swings⦿ Anti-epileptics
• Thought to decrease glutamate and increase GABA● Lamotrigine/Lamictal● 2012 adolescent maintenance Bipolar 1● Valproic Acid/Depakote● Carbamazepine/Tegretol● Oxcarbazepine/Trileptal
Pediatric Bipolar⦿ Diagnostic Controversy
• Irritability• NOS diagnosisBiological PredispositionPolypharmacy very common
Lithium⦿ Approval based on adult lit.⦿ Thought to alter
neurotransmission via NA transport
⦿ Requires labs at least every 12 weeks• Lith level• Renal function• TSH/T4• Lytes- CA
⦿ Pregnancy test⦿ Narrow therapeutic window (.
6-1.2)
⦿ Weight gain⦿ Tremor⦿ Dehydration⦿ Polyuria⦿ Thirst
• Heat• sports
Lithium Toxicity⦿ Tremor⦿ Ataxia⦿ Diarrhea⦿ Vomiting
Lithium⦿ Changing the preparation can address GI SE.⦿ Rapid discontinuation associated with increase
suicide risk⦿ NSAIDS increase plasma Lithium levels⦿ Youth are more likely to experience SE than
adults• Sports• Hydration
Lamotrigine/Lamictal⦿ Anti-seizure⦿ Maintenance tx of BP1-bipolor depression⦿ 100-200mg/day⦿ Brittle initiation/taper
• Skin rash ? Higher incidence in kids• If stopped for more than 5 days re-titrate• DC first sign of rash
⦿ 5 weeks to dose starting at 25mg day• Problem with erratic administration• Dose by half if using with VPA
⦿ No labs
Stevens Johnson⦿ Life threatening
necrotizing rash
⦿ More likely to occur if previous rash developed
⦿ Can result in amputation and death
Valproic Acid (VPA)⦿ Anti-Seizure⦿ Acute Mania⦿ Requires Labs⦿ Baseline
• LFT• Platelets
⦿ Levels
⦿ Not recommended in children under 10• PCOS● Infertility
⦿ Increase efficacy when used with Seroquel for mania• Weight gain
Carbamazepine/Tegretol⦿ Anti-seizure⦿ Acute mania- 13 years
older⦿ Requires Labs
• LFT• Renal• TSH/T3/4• Levels
⦿ Auto inducer/genetic predisposition
⦿ Inexpensive⦿ GI upset⦿ Bone marrow effects
• Minimized by conservative dosing
Oxcarbazepine/Trileptal⦿ Very similar to previous med but better
tolerated.⦿ Second and third line⦿ Off label in kids⦿ Strong inducer of other meds, careful of drug
drug interactions.⦿ Consider monitoring NA levels q 12 weeks
Toprimate/Topamax⦿ Anti-epileptic⦿ Migraines⦿ Off Label- Bipolar⦿ Binge eating
⦿ Sometimes used 2-3rd line with adolescents over 13
⦿ SE • GI upset• Metabolic acidosis• Kidney stones
ADHD⦿ Just a quick mention⦿ Focalin⦿ Tenex-Long Acting
Case Study 1⦿ J is a 14 year old 8th . He had an initial dx of ODD
at age 8. Parents sought treatment last year due to his “lack of energy”. He was given a dx of MDD, treated with CBT for 9 months with minimal positive effect. • Prescribed 10mg of Celexa, after 3 weeks the dose was
increased to 20mg.• Two days after dose increase became increasingly irritable
and had angry outbursts when re-directed.
What may be going on⦿ True diagnosis.
⦿ Medication Issue?
⦿ Potential School Implications.
Continuation⦿ On day 6 he begins cutting his arm with a fork,
later that evening his mother found him trying to tie a shoelace around his neck. When asked why or if he was suicidal he states “I wanted to see what would happen?”.
Ideas??⦿ What are some options regarding diagnosis and
next level of care?
References⦿ www.aacap.org⦿ Practice parameters⦿ Stahl (2012) The Prescriber’s Guide; Stahl’s
Essential Psychopharmacology