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Prescribing Guidelines for Child & Adolescent Behavioral
Health
Sonya Montgomery FNP-BC, PMHCS-BCFocus Behavioral Health
Asheville, NC 28803
National Nurse Practitioner Symposium2021
Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5
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Disclosures
No financial relationship with any commercial interest.
- S. Montgomery FNP-BC, PMHCS
Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5
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Learning ObjectivesDiscuss common psychiatric- behavioral health pediatric conditions and their presentation in the primary care setting.
Develop a safe and effective pharmacological treatment plan for managing behavioral health and identify the risks/benefits of psychotropic medications.
Utilize sound clinical judgement when referral to psychiatry or other treatment options are warranted.
Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5
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A Paradigm Shift in Pediatric Care
No longer fighting the bugs
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How troubled are children & youth in the U.S.????
THE FACTSSuicide 2nd leading cause of death in adolescents. Rates are up 56% since 2007.
Neuropsychiatric disorders in children have increased.
Children are not as responsive to medical treatments.
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Treatment Approaches
Therapies Behavioral, emotional,
educational, cognitive…….
Medications
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What are our concerns?
Developmental interactions
Long term adverse effects
Black box warnings
Off label prescribing
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FDA
Photo: Courtesy of Architect of the Capitol
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Antidepressant Studies
Fluoxetine (Prozac) Escitalopram (Lexapro) Sertraline (Zoloft) Fluvoxamine (Luvox) Duloxatine (Cymbalta) Vortioxetine (Trintellix)
5 of the above are approved by FDA for pediatric use.
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Children are not just “small adults.”
Developmental pharmacokinetics
*Metabolism & elimination differences*Cytochrome P450 differences*Absorption differs due to “gut” transit time*Less body fat*Higher extracellular water volume (newborn -12 y/o)
*Protein binding alterations
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Unique Pharmacokinetic Properties
Rapid elimination of drugs that utilize hepatic pathways
More efficient renal elimination (i.e. Lithium)
Dosing on body weight alone may lead to sub therapeutic concentrations
Hormonal changes influence drug concentrations & clearance
Blood level monitoring helpful
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Implications for dosing
Low dosing; bid dosing instead of dose increase for sub-therapeutic response.
Start low, titrate up slowly.
Do not rely on dosing strategies used in RCT studies. Study the literature on pharmacokinetic studies.
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Do we use the same medications?
Essentially, yes.
Mood Stabilizers Antipsychotics Antidepressants Antianxiety Alpha Agonists Stimulants
Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5
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Mood Stabilizers
Useful in cases of excessive irritability, unstable mood, & suboptimal or no response to antidepressants.
Diagnosis: DMDD, ODD, Conduct disorder, anxiety, depression.
Most of our guidelines for use are based on Pediatric studies for epilepsy, not psychiatric disorders.
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Mood Stabilizers
Valproic acid (depakote) Carbamzepine (tegretol) Lithium Oxcarbazepine (trileptal)
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Mood Stabilizers
Valproic Acid (Depakote) Starting dose:
<40 kg 250-500mg (750mg) >40 kg 500 mg (>1000mg)Titrate up q 3 days as needed
Labs: Monitor CBC, baseline LFTs, platelets,serum levels; (50 – 125 ug/ml)
Caution: Do not use in childbearing age females due to neural tube defects.Possible polycystic ovarian disease.
*Capsules for sprinkling available; valproic acid syrup.
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Mood Stabilizers
Carbamazepine (Tegretol)Dosing: <40kg 200mg QD (TD 400mg)>40kg 400mg QD (TD 800mg)Titrate up q 5 days as needed LABS: CBC, LFTs, blood levels weekly until
steady state (4-14ug/ml) Transient leukopenia; agranulocytosis within 1rst 3 months,
but rare. However should d/c med; may retrial later. * Capsules may be sprinkled, chewable & liquid formulations.
Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5
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Mood Stabilizers
Oxcarbazepine (trileptal) Similar to Tegretol, but fewer S/E.
Dosing: 300-600mg initially; titrate up to 900-1200mg daily (split dosing)
Risks of hyponatremia (Na levels) Serum levels for compliance issues or poor
responders Liquid & PO formulations
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Mood Stabilizers
Lithium Dosing:
<40kg 600mg/day (TD 600 -900mg/d) >40kg 900mg/day (TD 1200mg/d) LABS: CBC, BUN, Creat., U/A, thyroid function, EKG,
frequent serum levels (0.6-1.2 mEq/L) q 1-2 mos. Repeat thyroid & U/A q 3-6 months
FDA approved for mania >12y/o Caution: Lithium toxicity (>3.5 mEq/L) Metabolic syndrome Capsule, tablet, & liquid formulation.
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Mood Stabilizers: Third Generation
Lamotrigine (Lamictal) Topiramate (Topamax) Gabapentin (Neurontin)
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Mood Stabilizers: Third Generation
Lamotrigine
Recent studies have demonstrated efficacy in adolescent bipolar depression.
Not for use in children < 37lbs.(17kg). Dosing: Start low & titrate up very slowly q 14 days to
avoid rash. Caution: DVP increases serum concentrations; CBZ
lowers serum levels. Side effects? Well tolerated except 1% of pediatric pts.
developed a serious rash in clinical trials (greater than adult population)
If rash develops, evaluate immediately. Available in 5mg chewable, oral disintegrating and
tablets. Manufacturer warns against splitting tablets.
Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5
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Mood Stabilizers: 3rd Generation
Topiramate Adjunctive use primarily Dosing:
>40kg 12.5 - 25mg (TD 150mg/d) Titrate up q 7 days as needed. Monitor: Weight loss, cognitive S/E,
parathesias Caution: lowers oral contraceptive levels Migraine prophylaxis
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Mood Stabilizers: 3rd Generation
Gabapentin Dosing:
> 40kg = 300mg tid (TD 900-1800mg/d) Labs: Monitor serum levels for compliance
and/or poor response, (3.5- 10ml/L/d) Creat. clearance if renal impaired Inconclusive evidence of efficacy for pediatric
mood & anxiety disorders. Refractory use mostly.
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Antidepressants
SSRIs are still considered first line: Safe treatment of choice for…….
anxietydepression
irritabilityaggression
repetitive behaviorsself-injuriousbehaviors
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Antidepressants
2nd or 3rd line for treatment of ADHD/MOOD symptoms
Duloxotine (Cymbalta)Desvenlafaxine (Pristiq)Bupropion (Wellbutrin)Venlafaxine (Effexor)Vortioxetine (Trintellix)
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Antidepressant Studies
Fluoxetine (Prozac) Paroxetine (Paxil) Escitalopram (Lexapro) Sertraline (Zoloft) Fluvoxamine (Luvox)
2 of the above are approved by FDA.
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The Black Box Warning
Jan. 2006, Simon et al, found risk of suicide highest in the month prior to initiating antidepressant (AD) treatment, and risk declines after starting AD medication.
Sept. 2006, Leon: one of 36 youth suicides had antidepressant detectable in lab studies at autopsy.
April 2007, Bridge et al., restudied earlier data & included more data than previous study. Found the difference in SI between placebo & medicated group was 1%, not 2%.
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Did this create a problem?
April 2007, Nemeroff et al. report:
RX declined 10 – 20% following FDA warning.
Care “shifted” from generalists to specialists.
Rate of suicide in children/adolescents increased 18%.
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Antipsychotic Agents
Second Generation (Atypicals)
* Risperdone (Risperdal) 5 – 16 y/o* Paliperidone (Invega) 10- 17 y/o
* Iloperidone (Fanapt) 13 – 17 y/o
*Aripiprazole (Abilify) 6 – 7 y/o* Quetiapine (Seroquel) 10- 17 y/o
* FDA Approval
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Second Generation Atypicals
Ziprasidone (Geodon)Lurasidone (Latuda)Olanzapine (Zyprexa) 13- 17y/oAsenapine (Saphris) 10 - 17
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First Generation Antipsychotics
*Chlorpromazine 1 – 12 y/o *Loxapine 12 y/o and up *Perphenazine 12 y/o and up *Prochlorperazine 2 yrs/> 20 lbs. *Thiothixene 12 y/o and up. *Trifluperazine 6 y/o and up.
*FDA approved
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Expanded Use of Atypical Antipsychotics in Childhood
Schizophrenia of early onset
Bipolar disorder
Behavioral control
Autism Spectrum Disorder Conduct Disorder Oppositional Defiant D/O Mood Disorders
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Safety Considerations
*NEUROLOGICALEPSTardive Dyskinesia
*METABOLICWeight gainHyperlipidemiaElevated Prolactin
*CARDIACProlonged QT intervals
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Atypical Antipsychotics
EPS symptoms:
The atypicals are associated with less EPS at higher doses.
Add-on anticholinergics diminishes cognition. Do not use unless evidence of EPS.
The Bottom Line:AIMS testing.Start low, go slow.Optimal benefits with low dosing.
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Elevated prolactin
3.2 – 20 mcg/L in children.
Amenorrhea, gynecomastia, infertility Monitor levels in males & females Baseline & q 6 months Fasting lipids & glucose Seroquel best choice
Wfpsychbrain.wwik
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Atypical Antipsychotics: Metabolic Risks
Elevated glucose, cholesterol & triglyceride levels
Weight gain
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Atypical: Cardiac A/E
Prolonged QT intervals which may lead to fatal arrhythmias, (Geodon)
Hypotension & tachycardia due to a-adrenergic blockade with Risperidone & some FGAs.
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Stimulants
Amphetamine salts(Adderall, Adderall XR
Dextroamphetamine(Dexadrine,Dexadrine
Spansules)
Lisdexamfetamine(Vyvanse)
Methylphenidate(Ritalin, Ritalin SR,
Daytrana patch, Concerta)
Dexmethylphenidate(Focalin, Focalin XR)
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Other Choices
Methyphenidate D
Aptensio XR Quillichew ER Quillivant ER
Amphetamine D
Dyanavel XR liquid Adzenys XR-ODT Evekeo IR (ages 3 & up) Zenzedi IR (ages 3 & up)
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Newer Products
Adhansia (methyphenidate ER) Approved in ages 6y/o and up.Duration of 13- 16 hrs reported in RCTs.Dosing from 25- 85mg daily.No dosing equivalence to other methyphenidate products.
Jornay pm (methyphenidate ER)Approved in ages 6 y/o and up.Administer in the evening for a delayed release in the AM. Dosing from 20mg – 100mg daily (not equilivant to other methyphenidate products.)
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Stimulants: Safety & Efficacy
First line treatment of ADHD. Over 60 yrs. of research & clinical use. Stimulant treatment has generated the
largest body of literature for children: 3000 publications Over 200 RCTs
Recent studies addressing long term use: NIMH sponsored MTA study largest. Positive
outcomes r/t improvement & stability.
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Stimulants: Why the FDAWarning??
BLACK BOX warning on Amphetamines: Potential for abuse & diversion Potential for sudden death & serious
cardiovascular effects if the drug is misused
Warning on all Methylphenidate products: Cardiovascular risk for those with pre-existing
cardiovascular conditions.
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Stimulant Warnings
The warning is new: not the knowledge. Studies have always demonstrated minor
effects on BP & HR; pre-existing cardiac conditions always a contraindication.
Clarification & Formalization of Guidelines: Use is not recommended in children/adolescents
with known serious structural cardiac abnormalities, cardiomyopathy, serious arrhythmias.
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Stimulant Warnings
Listen to heart sounds every visit. Monitor v/s. PCP & mental health provider
collaboration necessary. Clearly review risks/benefits with Pt. &
family. Family hx of sudden cardiac death? ECG? (American Heart Assoc.- yes; American
Psychiatric Assoc.- no)
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Stimulant Alternative
Strattera (Atomoxetine)
FDA approved for ADHD; ADHD with anxiety. Best for ADD sxs., not hyperactivity. Labeling warns about possible effects on BP. GI side effects common. Recent warning added of increased suicidal
risk. Elevated LFT reported.
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Alpha-2 adrenergic agonists
Clonidine (Catapres, Kapvay)
Guanfacine (Tenex)
Guanfacine ER (Intuniv)
Effective for inattentiveness, hyperactivity, anxiety, insomnia, disruptive behavior, tic d/o, ASD symptoms.
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Alpha-2 adrenergic agents (clonidine, guanfacine)
First line treatment (off label) for:
Very young (ages <8)
High risk for weight loss or < 50 lbs.
Poor tolerance to stimulants
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Alpha-2 adrenergic agents
Utilized in children since 1970s. Prescriptions have increased seven-fold. Few studies, but efficacy is clearly
demonstrated. Monotherapy; or combination therapy with
other psychotropics. Cautious use with Methyphenidate,
antihypertensives, CNS depressants.
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Alpha-2 adrenergic agents
Guanfacine 1mg BID/TID Guanfacine ER 1mg – 6mg/day
Monitor for sedation, dizziness, dry mouth.
Clonidine 0.1mg HS/BID/TID up to 0.4mg/d
Clonidine ER 0.1mg BID up to 0.4mg/d
Formulation: Clonidine available in patch. Tablets for both may be broken.
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AND………………
Amantadine 100mg QD/BID/TID (dopamine agonist, glutamate inhibitor)
Useful for ADD sxs./anxiety/disruptive behavior.
Caution: doses 300mg/d or > raise seizure threshold.
May cause drowsiness initially. Start 50mg
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New product
Qelbree (Viloxazine) -multimodal agent -modulates 5HT2B & 5HT2C-Blocks NE
Viloxazine
5HTNEApproved
April 2021
5HT
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References
Aas, M. et al. Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders. Psychol. Med. 47, 902–912 (2017).
Bridge JA, Iyengar S, Salary SB, Barbe RP, Birmaher B, Pincus HA, Brent DA (2007). Clinical response and risk for reported suicidal ideation and suicide attemtps in pediatric antidepressant treatment. A meta analysis of randomized controlled trials. JAMA 297: 1683-1696.
CDC; National Center for Health Statistics 2020.
Cuffe, Steven P. (2009). Suicide and SSRI medications in children and adolescents: an update., American Academy of Child and Adolescent Psychiatry.
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ReferencesLeon AC, Marzuk PM, Tardiff K, Bucciarelli A, Piper TM, Galea S (2006). Antidepressants and youth suicide in New York City, 1999 – 2002. J Am Acad Child Adolesc Psychiatry45(9):1054-1058
Fleiss, Bobbi et al (2018). Early Origins of Neuropsychiatric Disorders, Pediatric Research 85, 113 – 117.
Nemeroff CB, Kalali A, et al (2007). Impact of publicity concerning pediatric suicidality data on physician practice patterns in the U.S. Arch Gen Psychiatry 64: 466-472.
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References
Olfson M, Blanco C, Lui SM, et al. (2012) National trends in the office-based treatment of children, adolescents and adults with antipsychotics. Archive Gen Psychiatry, 69:1247-56.
Simon GE, Savarino J, Operskalski B, Wang PS (2006).Suicide risk during antidepressant treatment. Am J Psychiatry 163: 41-47.
Slomiski, Anita. (2019). Chronic Mental Health Issues in Children Now Loom Larger than Physical Problems. JAMA 308.
Stahl, Stephen. Stahl’s Essential Psychopharmacology; Cambridge University Press; 2018.
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