Mental illness in Children and adolescents

Question 1

Depressive Disorders in children/adolescents

Question 2

Anxiety disorders in children/adolescents

Question 3

ADHD

Question 4

Substance use disorders in children/adolescents

Question 5

Autism Spectrum Disorder

Question 6

Psychotic Disorders in Children and Adolescents

Question 7

Prescribing recommendations for children:

Answer 7

-Accurate assessment
-Evaluate various child/adolescent’s contexts
-Obtain information from various sources( e.g. home and school)
-Be aware of pediatric pharmacokinetic principles
-Use psychotropics only for serious disruptive behaviors or symptoms
-Establish alliance with patient and parents
-Be aware that evidence of adults may not be the same for children and adolescents
-Maintain informed consent from responsible party and assent from patient
-Address the patient’s fears and resistance to psychotropics
-Consultations with other experienced clinicians are recommended

Question 8

Pharmacokinetics in children: Lipophilic medications

Answer 8

Lipophilic Medications:
Most psychotropic medications are highly lipophilic
The percentage of total body fat increases during the first year of life, then decreases gradually until puberty
Children have different volumes of fat for drug storage at different ages.

Question 9

Pharmacokinetics in Children: CYP/Metabolizing enzymes:

Answer 9

Both CYP450 and phase II drug metabolizing enzymes generally are absent in infancy, though rapidly develop over the first few years of life.
Toddlers and older children may have levels of these drug-metabolizing enzymes which exceed adult levels!
These decline until puberty, where they generally remain the same until adulthood.

Question 10

Pharmacokinetics in children: Liver mass effects

Answer 10

Relative to body weight, the liver mass of a toddler is 40-50% greater than an adult. A 6 year old’s liver mass is 30% greater than an adult.
Children tend to clear drugs more rapidly than adults
Children may require higher mg/kg concentrations to achieve the same plasma levels

Question 11

Pharmacokinetics in children: Renal Filtration

Answer 11

-By age 1, GFR and renal tubular mechanisms for secretion have reached adult levels
-fluid intake may be greater in children relative to adults
-medications have a more rapid renal clearance in children compared to adults

Question 12

Issues with Diagnosing Depression in Children and Adolescents:

Answer 12

Limited research conducted on children and adolescents
-Mood disorders may mimic other conditions (e.g. ADHD)
-Treatment of bipolar disorder

Question 13

What medications are used to treat depression in children?

Answer 13

SSRI’s and TCA’s.
-See table in PPT for specifics.
-Taper gradually to prevent withdrawal side effects.

Question 14

FDA approved medications for treatment of OCD

Answer 14

Clomipramine > 10 y/o
Fluvoxamine > 8 y/o
Sertraline > 6 y/o
Fluoxetine > 7 y/o

Medication Augmentation:
Clomipramine, Clonazepam, Neuroleptics, Add second SSRI, Lithium

Question 15

Non-OCD anxiety disorders:

Answer 15

Sertraline does not have FDA approval for treatment of anxiety disorders in childrenbut there is good evidence for its efficacy.
Medications should be dosed at rates done in clinical trials.
Typical dosages for sertraline based on CAMS study are 100-150 mg by week .
Typical dosage for fluoxetine are based on TADS and TORDIA studies. May titrate up to 40 mg by week 12.

Question 16

Oppositional Defiant Disorder:

Answer 16

No official medications approved by FDA for treatment
Best evidence is for psychotherapy and psychosocial interventions
Off-label use of stimulants (high comorbidity with ADHD), as well as mood stabilizers (Divalproex and Lithium)
Atypical Antipsychotics used as well (Risperidone has some evidence)
Bottom line: Treat with psychotherapy and use medications for any comorbid psychiatric disorders.

Question 17

Pediatric Bipolar I, Manic or Mixed.

Answer 17

Controversial diagnosis
Psychosocial interventions are necessary in addition to medications
Approved Medications by FDA for manic and mixed states in ages 10-17: Lithium, Quetiapine, Risperidone, Aripiprazole. Olanzapine has been approved to age 13 and up.
Off label use: Carbamazepine, Divalproex in monotherapy and as augmentation to approved meds, Ziprasidone, and Clozapine
Topiramate and Oxcarbazepine only have negative studies in children, DON”T USE THEM!!

Question 18

Diagnostic criterial for ADHD in children:

Answer 18

Onset usually by seven years old
Many theories exist to etiology
Potentially linked to pre-frontal cortex neurodevelopmental abnormalities
Dopamine and other neurotransmitters linked to development of ADHD
Environmental factors may play role
Diagnosed by various healthcare professionals
Characterized by inattentiveness, impulsivity, and hyperactivity

Question 19

Atomoxetine for ADHD in children.

Answer 19

Selective NE reuptake inhibitor
Advantages:
low abuse potential
less insomnia
Less growth problems
Disadvantages:
delayed onset of effect (2-4 weeks)
lower efficacy than stimulants
Starting dose: Starting dose 0.25 mg per pound for children and adolescents weighting less than 154 pounds
Dose based on weight: 0.5mg/kg/day, up to 1.2mg/kg/day as tolerated
Adverse effects: nausea, stomach pain, moodiness, increased heart rate, Black Box – suicidality

Question 20

Bupropion for ADHD

Answer 20

NE reuptake and DA reuptake inhibitor
Dosing is somewhat unclear in children

Question 21

What are the Alpha-adrenergic agonists for ADHD

Answer 21

May strengthen working memory by improving functional connectivity in prefrontal cortex

Question 22

Guanfacine

Answer 22

Guanfacine (Intuniv) more selective for A2a receptor (long acting)
less sedation and dizziness than clonidine
2-4 mg with effect between 2-4 weeks

Question 23

Clonidine

Answer 23

Clonidine (Kapvay – Catapress)less effective than stimulants, used as adjunct to manage tics, sleep problems and aggression

Question 24

Methylphenidate vs. amphetamine:

Answer 24

Methylphenidate vs. Amphetamine:
Methylphenidate blocks the reuptake of DA and NE but has little effect on presynaptic release of dopamine
Amphetamine blocks reuptake of DA and NE and increases release of DA and NE
Long Acting Forms - 3 delivery options:
SODAS (Spheroidal Oral Drug Absorption Systems) and Diffucaps= combination of immediate and extended release beads
OROS (Osmotic Release Oral System): capsule with H2O permeable holes which release medication depending on osmotic pressure
3rd option: Lisdexamfetamine, a prodrug bound to L-lysine which uses GI tract to metabolize  dextroamphetamine

Question 25

Methylphenidate: Ritalin

Answer 25

FDA approved stimulant
Blocks transporters of NE and DA
Prevents reuptake of NE and DA
Available in immediate and control released dosages
Initial dose 2.5 mg
If not effect, weekly increments of 2.5 mg to 5 mg
Multiple doses during the day may be required
Long acting forms available (Concerta)

Question 26

Amphetamine(Adderall)

Answer 26

FDA approved stimulant
Blocks transporters of NE and DA slightly different than methylphenidate
Prevents reuptake of NE and DA
High doses may be linked to abuse
Initial dose of 2.5 mg to 5 mg
Weekly increments may be required
Multiple doses during the day may be required

Question 27

Stimulant side effects:

Answer 27

Decreased appetite
Weight loss
Sleep disturbances
Irritability
Headache
Palpitations, jitteriness
Sweating and flushing
Motor tics

Question 28

Practical Steps in Stimulant Treatment

Answer 28

Refer to handouts for dosing information
Can titrate with short acting as needed on top of long acting
Base your clinical decisions on the best interests of the child
Adverse effects:
Common: nausea, stomach upset, decreased appetite, insomnia, headache
Uncommon: motor tics , dysphoria, irritability, hallucinations, “zombie-like” appearance
Cardiac: 25 cases of sudden death
Growth: MTA study – 1cm/year decrease in height over 1-3 yrs. of continuous treatment

Question 29

Autism Spectrum Pharmacotherapy:

Answer 29

NO medications approved for core symptoms
Medications often used to treat related symptoms, such as depression, anxiety, and aggression
Aggression: Risperidone is FDA approved
Methylphenidate, Clonidine and naltrexone have preliminary data
Insistence on Sameness: Lexapro has preliminary efficacy data
Anxiety: often use SSRIs, at low doses
Patients with autism are often very sensitive to adverse effects, even at low doses

Question 30

Treating schizophrenia in children and adults:

Answer 30

Atypical antipsychotics are first line treatment for psychosis in children and adolescents:
Aripiprazole
Olanzapine
Quetiapine
Paliperidone (ages 13-17 years old)
Atypical antipsychotics are not approved for use in children under 5 years old

Question 31

Treating Substance use Disorder in Children and adolescents:

Answer 31

-No medication is FDA approved for treatment of Substance Use Disorder in children
-There are scant studies which show the efficacy of using medications to treat SUD in adolescents
-Drugs prescribed will be used off label for opioid, alcohol or nicotine use disorder
-There are limited studies which show the neurobiological impact of the use of the off label drug treatment

Question 32

Treating Opioid use disorder in children and adolescents

Answer 32

buprenorphine, methadone, naltrexone
Suboxone and subutex recommended.

Question 33

Treating Alcohol use disorder in children and adolescents

Answer 33

Acamprosate, disulfuram, naltrexone

Question 34

Treating nicotine use disorder in children and adolescents

Answer 34

Chantix, bupropion, nicotine replacement therapy.