This is an introduction to pediatric psychopharmacology. Presentation done on July 25th as a part of the nuts and bolts lecture series. Thanks to all the chief fellows over the last 6 years who have contributed to the development of these slides. Please refer to scientific literature for accuracy. This can serve as a rough guide to pediatric psychopharm for child and adol psychiatry fellows as well as residents, and medical students. If you have any questions please feel free to send them my way at pallavpareek@gmail.com

1. Pediatric Psychopharmacology
July 25th 2012
Pallav Pareek M.D.
(Initial writings & contributions from the
various chief fellows over the years)

2. Pharmacokinetics: children are not little adults !!
• Pharmacokinetics: constitutes
absorption, distribution,
metabolism, and excretion
• Gastric absorption
– Stomach contents are less acidic, so weakly acidic
drugs may be absorbed less efficiently
• Distribution
– Most neuroleptics and antidepressants are
lipophilic (less body fat)
• Antipsychotics, TCA’s and Lithum
eliminated more rapidly
• Metabolism
– Increased hepatic metabolic capacity and more
efficient renal clearance

3. Before Starting Medications
• Physical exam: height, weight, vitals and
abbreviated neurological exam
• Labs may be required:
– CBC, CMP, UA/UDS, TSH
– Urine HCG in females of reproductive age
– Fasting lipids and glucose
– May consider lead level, karyotype and/or specific
chromosomal analysis if MR is suspected

4. Treatment of ADHD : Atomoxetine
• Brand name Strattera ®
• Available as 10,18,25,40,60
mg caps
• FDA approved for ADHD in
children
• Is a Sert, Ne, da reuptake
inhibitor
• CYP2D6 substrate
• Half life: 5 hours

5. Strattera ® Fun facts
• Eli Lilly first postulated
this as a depression rx
• Failed clinical trial (trade
secret): retried and
submitted to FDA for
ADHD
• Time to response : 1 » 6
weeks
• Use in patients with
depressive symptoms
• Initial name tomoxetine ,
changed to atomoxetine
as per FDA
recommendations

6. Strattera word of caution
• Liver damamge
• FDA warning for monitoring mood change
• Can increase BP/HR on initiation, caution in
known heart disease
• Induction of mania, suicidal thoughts/behaviors
• Can precipitate seizures in combination with
tramadol
• Increased levels when co-administered with
paroxetine and fluoxetine (CYP2D6)
• MAOIs contraindicated

7. α-2 adrenergic agonists
• First developed an antihypertensive
agents
• Fisrt used in child psychiatry 70’s for
tics, TS
• Dramatic increase last two decades
• MOA » Initially thought to be
through presynaptic α2A receptors
in LC firing and NE release. Now
proposed postsynaptic action on PFC
α2A receptors.

8. α2-adrenergic agonists contd:
• Clonidine: • Guanfacine:
• Available as • Only available orally as
0.1,0.2,0.3mg tabs and 1,2,3,4 mg tabs
eqv dose patch system • Roughly ten times less
(1 week) potent
• Starting dose 3-5 • Start at 0.5 mgbid ↑ to
μg/kg/day t/qid
• ↑ by 0.05 per 3 days • ↑ 0.5mg/3d
• Max dose : 0.4 • Max: no studies for
dosages above 4mg/d

9. Adverse Effects
• Clonidine: Dry mouth, drowsiness, sedation,
weakness, fatigue, hypotension, bradycardia
• GXR has similar but less pronounced s/e profile
• Patch: dermatitis (hydrocortisone)
• CV complications
Scenario 1: low BP, low pulse » ↓ Clonidine
Scenario 2: tachycardia, tachypnea, fever(+/-)
anxiety panic, acute mental status changes,
reinstate dose and gradually taper

10. Stimulants
• MTA: Multimodal treatment
study of children with ADHD
• 14 month study: 579 children
• Pharmacological(P) vs.
behavioral(B) vs.
combined(P+B) vs. controls
• P much superior than B, not
much differnce P+B

11. Stimulants
• Two families of stimulants MPH preperations and
Amphetamine preperations
• 1st use in children for ADHD as early as 1930’s
• Well established role 1970’s
• Global use of stimulants have ↑ 3 fold 1993-2003
(Scheffler et. al 2007)
• 80% of worldwide stimulant use is in US
• 2003: 2.5 million children 4-17 in the US receiving
stimulants (CDC)

12. Stimulants contd:
• Methylphenidate and Amphetamine preparations
are the two main families of stimulants
• MOA: not known, but proposed enhancement of
NE and DA transmission
• Both MPH and AMPH are racemic mixtures of D
or L enantiomers
• Only D enantiomer: D-MPH i.e. Focalin D-AMPH
i.e. Dexedrine
• D&L enantiomer mixture: Ritalin or Adderall

13. Methylphenidate preparations

14. Amphetamine preparations

15. Should I order an
EKG before starting
a stimulant

16. AACAP & APA verdict1
• American Academy of Child and
Adolescent Psychiatry (AACAP) and
the American Academy of Pediatrics
(AAP) have concluded that sudden
cardiac death (SCD) in persons
taking medications for ADHD is a
very rare event, occurring at rates
no higher than in the general
population of children and
adolescents. Both of these groups
also note the lack of any evidence
that the routine use of ECG
screening before beginning
medication for ADHD treatment
would prevent sudden death.
1: Cardiovascular Monitoring and Stimulant Drugs for Attention-
Deficit/Hyperactivity Disorder (AAP May2008)

17. Stimulants: Adverse Effects
• Appetite suppression, growth delay
– Reduction in growth velocity that reverses when stimulant is discontinued,
no effect on ultimate height
• Insomnia
– Decreased sleep efficiency and REM sleep
– Increase in stage 1 and 2 sleep
• Blood pressure and heart rate changes
– Risk of sudden death
• End-of-dose withdrawal/rebound
• Stimulant side effects generally worse in younger
populations, e.g. preschoolers

18. When should stimulants be avoided ?
• Cardiomyopathy
• Serious structural or rhythm abnormalities
• Add behavioral rx in kids with anxiety
• Package inserts: contraindicate in seizure
disorder (no evidence base for this warning)
• Uncontrolled epilepsy

19. Antidepressants

20. MAO Inhibitors
• Last youth trials
have been more
than a decade and
a half ago
• Currently minimal
enthusiasm
amongst clinicians
and researchers
due to plethora of
available options
• Cheese reaction →

21. Tricyclics
• FDA approval
– Depression and Anxiety in ages 12 and up (Doxepin)
– Also used to treat enuresis 6 (Imipramine)and OCD 10(Clomipramine)
• Considered “third-line” for ADHD
• Used to treat chronic pain/headaches
• Sudden death in 8 children—thought to be
cardiac related
– Check baseline ECG

22. TCA’s continued

23. SSRI’s
• FDA approval for MDD, OCD
– Fluoxetine approved for use in MDD in 8+
– Escitalopram approved for use in MDD ages 12-17
– Sertraline, Fluvoxamine approved for use in OCD
– Preferred treatment for MDD in
children/adolescents
• Less SE’s
• Overdose less problematic
• Once daily dosing in most
– Black-box warning

24. SSRI’s and Suicidality
• 2003: Great Britain’s department of health
issued statement :Paxil in 18 yr and younger
• 2004: FDA: All SSRI’s Black-box warning 18 &↓
based on analysis of data indicating 4% ↑
suicidal thoughts on SSRI’s as compared to 2%
PBO (Hammad et. al. 2006)
• TADS: Fluoxetine (F) vs. CBT(C) vs.
Combination (Cb) vs. Controls (Pbo): 12 week
trail » F-9.2%, C-4.5%, Cb-4.7%, Pbo-2.7%

25. Things to remember re: SSRI’s
• Suicidality: always discuss with parents and
explain
• Switch to Mania: discuss R/B analysis
• Serotonin Syndrome: rigidity, myoclonus, hyper-
reflexia, autonomic instability, hyperthermia,
agitation, delirium
• Discontinuation syndrome
• Drug interactions: Pimozide & Atomoxetine (paxil
and prozac 2D6) ↑levels, Tramadol ↓ seizure
threshold

26. Mood Stabilizers

27. Lithium
• Gold Standard
• 1st used 40 yrs ago in children
• Lithium carbonate is a naturally occuring
salt.
• FDA approved: mania 12 & older
• MOA: Multiple complex mechanisms
mostly at second messenger level
• Half life in children: ~18 hours
• Recommended dose: 30 mg/kg/d
• Levels: 0.8-1.2 meq/L

28. Recommended testing
• Baseline: BUN/creatinine, electrolytes, serum
Calcium, TFT, CBC
• Repeat RFT: every 3 months till 6 mo
• Repeat TFT: once in first 6 months
• Repeat all labs, as needed/symptomatic,
repeat serum calcium/year.
• Lithium levels: trough value without morning
dose, can do as early as 5th day.

29. Trivia !!
• Historically which soft-drink contained lithium
as one of it’s ingredients

31. Valproic Acid
• FDA approved
– Acute mania (up to 3 weeks) in patients over the age of 18
– Migraine prophylaxis in patients over 16
• Dosing: Start at 15mg/kg/day
• Testing: CBC, platelet, LFT at baseline, repeat every 6 mo
• Cautions
– Severe or fatal hepatotoxicity, esp. for children under age 2
– Teratogenic (neural tube defects)
– PCOS, elevated serum testosterone in females under age 20
– Co-administration with clonazepam may induce absence seizures
– Co-administration with guanfacine may increase VPA levels
– Co-administration with lamotrigine may increase lamotrigine levels (PRITE)

32. Carbamazepine
• FDA approved
– Any age for seizures
– Tegretol XR approved for bipolar mania in adults
• Cautions
– Follow CBC, LFTs, carbamazepine level
– Bone marrow suppression
– Sedating
– Can be teratogenic (neural tube defects)
– Strong potential for drug interactions
• Dosing
– Children greater than 8 years: 15mg/kg/day divided TID with target
dose achieving level of 7-10 mcg/ml
– Adolescents: 200 mg BID to start with treatment doses ranging from
600-1600 mg/daily divided BID and target level of 8-12 mcg/ml

33. Lamotrigine
• FDA approved for
– Adjunct use for epilepsy in children > age 2
– Bipolar in adults but not kids
• Cautions
– Serious skin reactions in 1% of patients <16 are most likely to happen
within the first 8 weeks.
• Fever, swollen LN’s, sores of mouth, eyes, lips or tongue all may
require D/C of med.
• Dosing
– 25 mg/day x 2 weeks; double for 2 weeks; increase by 50 mg/day
every 1-2 weeks
– Typical target for Bipolar Disorder 100-200 mg/day

34. Crux of the Story !!
• Other options include: oxcarbazepine,
topiramate, gabapentin, pregabalin
• All research to date indicates: Evidence is
strongest for lithium, somewhat strong for
valproate, and weaker for others
• Lithium and VPA are also neuro-protective
with more evidence for Lithium, also reduces
suicidality (Chuang t. al. 2004)

35. Antipsychotics
• Typicals: Around longer; more experience in
kids.
– FDA approved for use in children
– Studied in ADHD, MR, ASDs and movement
disorders
– Concern for more extrapyramidal side effects and
tardive dyskinesia

36. Second generation Antipsychotics
FDA approved
 Psychosis, mood stabilization in patients over 18
yrs
Primary Psychosis in kids is RARE
 1-2/10,000 in ages <15 yrs; boys outnumber girls
by approximately 2:1.
 Childhood schizophrenia appears to be genetically
related to the adult type of schizophrenia.
Used to treat aggression, irritability in multiple diagnoses
Have been studied in MR, autistic populations, Bipolar Disorder

37. SGA’s

38. Desmopressin DDAVP
• FDA approved
– Primary nocturnal eneuresis (ages 5-17)
– Central DI
• Enuresis
– 80% of cases are “primary”
– Untreated, remission rate is 10-20% per year
– Associated with ADHD, comorbid developmental delays and
encopresis
– To dx: must be at least age 5, 2x/week for 3 consecutive months
• Dosing
– 20 micrograms or 0.2 ml nasal spray divided between nostrils at
HS, can decrease to 0.1 ml if effective
– 0.2 mg tab at HS
– Max 0.6 mg at HS

39. Insomnia treatment
• Benzos / Z drugs(acting
through the GABAergic
transmitter) Best avoided
• Melatonin : pineal hormone→
• Remelteon (Rozerem) MT1 &
MT2 receptor agonist:
available as 8mg tab →
• Mirtazapine
• Trazodone

40. Thank You !!