Pediatric Psychopharmacology

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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

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Pediatric Psychopharmacology

  1. 1. Pediatric Psychopharmacology July 25th 2012Pallav Pareek M.D.(Initial writings & contributions from the various chief fellows over the years)
  2. 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. 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. 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. 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. 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. 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. 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. 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 complicationsScenario 1: low BP, low pulse » ↓ ClonidineScenario 2: tachycardia, tachypnea, fever(+/-) anxiety panic, acute mental status changes, reinstate dose and gradually taper
  10. 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. 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. 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. 13. Methylphenidate preparations
  14. 14. Amphetamine preparations
  15. 15. Should I order anEKG before starting a stimulant
  16. 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. 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. 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. 19. Antidepressants
  20. 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. 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. 22. TCA’s continued
  23. 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. 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. 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. 26. Mood Stabilizers
  27. 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. 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. 29. Trivia !!• Historically which soft-drink contained lithium as one of it’s ingredients
  30. 30. 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)
  31. 31. 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
  32. 32. 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
  33. 33. 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)
  34. 34. 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
  35. 35. Second generation AntipsychoticsFDA approved  Psychosis, mood stabilization in patients over 18 yrsPrimary 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 diagnosesHave been studied in MR, autistic populations, Bipolar Disorder
  36. 36. SGA’s
  37. 37. 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
  38. 38. 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
  39. 39. Thank You !!

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