Child and Adolescent Psychopharmacology

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Child and Adolescent Psychopharmacology

• Clinical Issues

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Treatment issues in common psychiatric disorders
including

• ADHD
• Major Depression
• Bipolar Disorder
• Psychotic disorders
• Anxiety Disorders/OCD
• Tic disorders

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General Concepts

• Metabolic issues- May require higher weight
  adjusted dosages
• Probable Heterogeneity of diagnoses (e.g. Bipolar
  disorder)
• Developmental Differences
• Address Contraceptive issues
• Avoid rapid switching (up to 8 wks for
  antidepressant effect)

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General Concepts (cont)

• Comorbidity
• Regulatory issues (FDA Approval, warnings)
• Off label use common
• Medication interactions
• Medications generally one component of treatment
  (psychotherapy, behavioral)

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Target symptoms

• Avoid empiric treatment when possible
• Target symptoms based on diagnosis
• Clinical interview/direct observation
• Collateral history-Family, teachers
• Rating scales-Conners, Beck, etc.
• Computerized testing

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Choice of drug

• Class A- Good empiric support, RCTs (eg.
  Fluoxetine-depression, stimulants-ADHD)
• Class B- Fair empiric support, positive but
  inconsistent in RCTs, small sample trials
  (clonidine for tics, fluoxetine for OCD, etc)
• Class C- minimal empiric support, case studies,
  open-label trials (newer meds)

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Risk-Benefit Ratio

• Informed consent critical
• Process, not a document
• Utilize patient education materials (FDA website,
  AACAP Facts for Families, etc.)
• Reinforce importance of decision, encourage
  understanding of rational

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Documentation of Informed Consent

• Who was present, readiness to learn
• Alternative tx options
• Predisposing factors
• Common, less common, rare but serious
• Cover toxicities, potential fatal outcomes, Black
  Box Warnings as applicable
• Indicate process, questions, understanding
• Consent/assent statement
• Questions
• Withdrawal without prejudice

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ADHD

• Stimulants remain the mainstay
• Atomoxetine (SSRI) second line
• Others-
• Clonidine
• Guanfacine
• Bupropion

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ADHD- Stimulants

• Two major groups- methylphenidate and
  dextroamphetamine/mixed salts.
• Lisdexamfetamine dimesylate (prodrug)
• Mechanism of action- increased dopamine (DA)
  release, decreased reuptake. Possible secondary
  norepinephrine effects
• Increased attention/decreased off task motor
  activity
• Non-specific attention issue

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ADHD Stimulants

• SEs include appetite suppression, GI upset
  (mild), HAs, tic exacerbation
• FDA warnings include cardiovascular (arrythmia-
  sudden death with Adderall), behavioral,
  psychosis
• Black Box- abuse potential

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ADHD others

• Atomoxetine (Strattera)- SSRI- second line- 2
  cases of hepatic damage
• Clonidine- less robust, concern for rebound HTN
• Bupropion (Wellbutrin)- Possible Utility in
  adults, substance abuse, etc.

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Major Depression

• SSRI s the mainstay- Includes
  fluoxetine, sertraline, citalopram, escitalopram
• FDA approval- fluoxetinedepression, fluoxetine,
  sertraline, fluvoxamine- OCD
• Others- Bupropion, venlafaxine, TCAs

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Depression-SSRIs

• Mechanism of action- block reuptake of serotonin
• SEs mild- include GI distress, HA, sweating.
  More severe- irritability, behavioral
• Watch drug interactions (cP450 enzyme)
• Black BoxWarning for suicidality

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Black Box Warning for Suicidality

• Data from initial clinical trials- Twice as
  likely as placebo to have
  suicidal thoughts or behaviors
• Possible explanations- Improvement
  Misdiagnosed? Irritability With
  drawal syndrome

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Bipolar disorder

• Three classes of medications used clinically
• Traditional mood stabilizer- LiC03
• Anticonvulsants-valproate, carbamezapine,
  lamotrigine, topirimate
• Atypical antipsychotics (including risperidone,
  quetiapine, olanzapine, ziprasidone)

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Bipolar disorder-LiC03

• FDA approved age 13 and up
• Mechanism- evidence of multiple neurotransmitter
  effects (dopamine, serotonin, acetylcholine, NE,
  and GABA) Common SEs- thirst, GI, taste
• More troubling- tremor, acne
• Significant- renal, thyroid, ? Teratogenic

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Bipolar Disorder- LiCO3 (cont)

• Med interactions- note ibuprofen
• Narrow therapeutic window (approx 0.5-1.2 meQ/L)
• Monitor renal and thyroid function
• Compliance critical, Some evidence of loss of
  efficacy with non-compliance

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Bipolar disorder-Anticonvulsants

• Valproate
• Off label use- few rigorous studies
• Mechanism likely involves GABA, Protein kinase
  C, possibly kindling
• Monitor levels
• Common SEs- sedation, wt gain, GI
• Rare/Serious SEs-Teratogenic (neural tube),
  ?PCO, Hepatic damage, pancreatitis

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Bipolar disorder- Anticonvulsants

• Carbamezepine- off label- literature limited
• Autoinduction, leukopenia, rash, aplastic anemia,
  thrombocytopenia- use more infrequent
• Third Generation- Lamotrigine, Topirimate-
  literature limited, some promising info.
  Significant SEs include rash with Lamotrigine,
  weight loss with Topirimate

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Bipolar disorder- Antipsychotics

• Typical APs (haloperidol, fluphenazine) less
  used-Atypicals more common-
• Includes risperidone, quetiapine, olanzapine,
  ziprasidone-
• Mechanism- D2 blockade 5HT2 effects

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Bipolar disorder-Antipsychotics (cont)

• Common SEs- Dry mouth, blurry vision,
  constipation, sedation, wt gain (except
  ziprasidone)
• Rare/Serious- association with DM (particularly
  olanzapine), Movement d/o, EPS, NMS, ?Tardive
  dyskinesia
• Monitor with ADA guidelines- wt, waist, BMI

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Psychotic disorders

• Schizophrenia, Schizophreniform disorder-
  Atypicals the mainstay
• Schizoaffective disorder- Combination mood
  stabilizer, Atypical antipsychotic- Similar to
  bipolar strategy

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Anxiety disorders including OCD

• Fluvoxamine and sertraline approved for use in
  juvenile OCD
• Other anxiety disorders (panic d/o, GAD) low dose
  SSRIs most commonly used
• Start low, go slow (activation, increased anxiety
  a possibility)
• Benzodiazepines may have some utility-
  risk-benefit ratio must be considered
  (clonazepam)
• ? Buspirone

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Tic disorders

• Includes Tourettes, motor, vocal and transient
  tic disorders
• Use of haloperidol, pimozide supported by
  literature
• Most clinicians choose newer atypicals to reduce
  risk of EPS. Controlled trials needed
• Clonidine, Guanfacine may be useful

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Pervasive Developmental Disorders

• Autism, Aspergers D/O, Childhood disintegrative,
  Retts, NOS
• Literature supports typical antipsychotics
• Like tic d/os atypicals more common
• Risperdal Recently approved
• Associated disorders- depression, consider SSRI
• Stimulants controversial- May worsen?

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Summary

• Clarify diagnosis
• Choice of agent based on best evidence
• Education, informed consent essential
• Follow closely
• Utilize adjunctive therapy where appropriate
• Be conservative and careful- avoid rapid switch,
  polypharmacy only when appropriate, keep up with
  literature