3UHVFULELQJ *XLGHOLQHV IRU &KLOG ...npsymposium.com/wp-content/uploads/2021/05/A5-Pediatric...Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5 3 $ 3DUDGLJP 6KLIW LQ

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


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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.


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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


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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.


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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.


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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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Stimulant Medications


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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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Questions/Comments


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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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Documents

3UHVFULELQJ *XLGHOLQHV IRU &KLOG ...npsymposium.com/wp-content/uploads/2021/05/A5-Pediatric...Pediatric Psychopharmacology Sonya Montgomery FNP-BC, PMHCS-BC A5 3 $ 3DUDGLJP 6KLIW LQ