Child Psychopharmacology

1. Overview of Child Psychopharmacology
   1. Key Points
2. Selective serotonin reuptake inhibitors
   1. Key Points
   2. Management
3. Tricyclic Antidepressants
   1. Key Points
   2. Management
4. Atyptical (novel) antidepressants
   1. Key Points
   2. Management
5. Stimulants
   1. Key Points
   2. Management
6. Anxiolytics
   1. Key Points
   2. Management
7. Alpha Agonists
   1. Key Points
   2. Management
8. Mood Stabilizers and Anticonvulsants
   1. Key Points
   2. Management
9. Antipsychotics
   1. Key Points
   2. Management
10. Medication Tables
    1. SSIRs
    2. SSIR Research
    3. Tricyclic Antidepressant Preparations
    4. Types of Stimulants
    5. Commonly Prescribed Psychotropic Medications for Children
11. Resources for Parents
12. References

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• Black box warning: The FDA has recently added a black box warning on all antidepressant medications warning of the risk of suicidal behavior. This is the strongest warning short of banning a drug. A recent AACAP report states there is a there is a "consistent increase in risk ratio of about 1.5-2 among all the antidepressants"(Cuffe, 2004). This translates into 2-3 adolescents per 100 evidencing suicidal ideation or behavior. But this black box warning has been controversial since suicide rates among children untreated depression (among adults) may be higher. The benefit-ratio of medication treatment for each child should be assessed on an individual basis as untreated depression may be more harmful. The risks and benefits of medication should always be discussed with parents. Combination treatment with psychotherapy has the most evidence for positive outcome. For the Black Box warning go to http://www.fda.gov/cder/drug/antidepressants/labelTemplate.pdf.
  The FDA has recently added a black box warning on all antidepressant medications warning of the risk of suicidal behavior. This is the strongest warning short of banning a drug. A recent AACAP report states there is a there is a "consistent increase in risk ratio of about 1.5-2 among all the antidepressants"(Cuffe, 2004). This translates into 2-3 adolescents per 100 evidencing suicidal ideation or behavior. But this black box warning has been controversial since suicide rates among children untreated depression (among adults) may be higher. The benefit-ratio of medication treatment for each child should be assessed on an individual basis as untreated depression may be more harmful. The risks and benefits of medication should always be discussed with parents. Combination treatment with psychotherapy has the most evidence for positive outcome. For the Black Box warning go to http://www.fda.gov/cder/drug/antidepressants/labelTemplate.pdf.
• well tolerated and non-lethal in overdose: Wilens et al 1999 demonstrated hemodynamic and ECG safety, cardiovascular safety.
  Wilens et al 1999 demonstrated hemodynamic and ECG safety, cardiovascular safety.
• combination of Fluoxetine and Cognitive Behavioral therapy most effective treatment: The Treatment for Adolescents with Depression Study (TADS; 2004) examined the efficacy of various depression treatment combination on 439 adolescents. Results indicate that the combination treatment (CBT + fluoxetine) was significantly more effective than placebo, fluoxetine alone or CBT alone. The rates of positive response were: 71% for combination fluoxetine and CBT; 61% fluoxetine alone; 43 % CBT alone; 35 % CBT with placebo.
  The Treatment for Adolescents with Depression Study (TADS; 2004) examined the efficacy of various depression treatment combination on 439 adolescents. Results indicate that the combination treatment (CBT + fluoxetine) was significantly more effective than placebo, fluoxetine alone or CBT alone. The rates of positive response were: 71% for combination fluoxetine and CBT; 61% fluoxetine alone; 43 % CBT alone; 35 % CBT with placebo.
• significant reduction in suicidal ideation: However, Fluoxetine alone showed the smallest reduction in suicidal ideation and Fluoxetine treated adolescents had a significantly higher rate of "harm related events", including suicidal attempts. Together these findings suggest that combination treatment be strongly encouraged.
  However, Fluoxetine alone showed the smallest reduction in suicidal ideation and Fluoxetine treated adolescents had a significantly higher rate of "harm related events", including suicidal attempts. Together these findings suggest that combination treatment be strongly encouraged.
• Recent research shows that Sertraline alone was more effective than placebo: The Pediatric OCD Treatment Study (POTS) was a RCT that included 112 patients aged 7-17 with OCD in 3 academic centers.
  The Pediatric OCD Treatment Study (POTS) was a RCT that included 112 patients aged 7-17 with OCD in 3 academic centers.
• Fluoxamine - efficacy: RUPP Anxiety Study Group; Well tolerated, more GI symptoms.
  RUPP Anxiety Study Group; Well tolerated, more GI symptoms.
• Paroxetine - more effective: 5% Insomnia, decreased appetite, vomiting
  5% Insomnia, decreased appetite, vomiting
• suicidal ideation and behavior: Suicidal ideation and behavior among children may include a broad range of thoughts and behaviors, including direct statements ("I want to kill myself"), indirect statements ("Nobody will miss me"), intentional self-harm (e.g., scratching, cutting, burning), dangerous behavior (e.g., running into traffic, unprotected sex, jumping from heights), harm to animals, acting out, violent behavior, death-themed artwork/journaling or joking about death.
  Suicidal ideation and behavior among children may include a broad range of thoughts and behaviors, including direct statements ("I want to kill myself"), indirect statements ("Nobody will miss me"), intentional self-harm (e.g., scratching, cutting, burning), dangerous behavior (e.g., running into traffic, unprotected sex, jumping from heights), harm to animals, acting out, violent behavior, death-themed artwork/journaling or joking about death.
• Fluoxetine: Approved for children 7 and older for OCD & depression. In the recently completed Treatment for Adolescents with Depression Study (TADS) funded by NIMH, suicidal thinking generally decreased during treatment with fluoxetine, but 15 of the 216 youths on fluoxetine (6.94 percent) had a suicide-related event, such as a suicidal attempt or threats, as compared with 9 of the 223 on the inert placebo pill (4.04 percent).
  Approved for children 7 and older for OCD & depression. In the recently completed Treatment for Adolescents with Depression Study (TADS) funded by NIMH, suicidal thinking generally decreased during treatment with fluoxetine, but 15 of the 216 youths on fluoxetine (6.94 percent) had a suicide-related event, such as a suicidal attempt or threats, as compared with 9 of the 223 on the inert placebo pill (4.04 percent).
• Fluvoxamine: Approved for children 8 and older for OCD.
  Approved for children 8 and older for OCD.
• Sertraline: Approved for children 6 and older for OCD.
  Approved for children 6 and older for OCD.
• Clomipramine: Approved for children 10 and older for OCD.
  Approved for children 10 and older for OCD.
• Desipramine: Not approved for use in children.
  Not approved for use in children.
• Imipramine: Approved for children 6 and older for bedwetting.
  Approved for children 6 and older for bedwetting.
• Monitoring: Careful consideration of personal or family history of premature cardiac disease, conduction deficit, and cardiac structural anomalies rhythm disturbances.
  Careful consideration of personal or family history of premature cardiac disease, conduction deficit, and cardiac structural anomalies rhythm disturbances.
• Bupropion (Wellbutrin): Wellbutrin is a novel aminoketone that is structurally similar to amphetamines. Dopamine uptake>Norepinephrine uptake. Formulary is short acting (75 and 100 mg tid), sustained release (100, 150, 200 mg b.i.d.) or extended release tablets ( 150 and 300 mg daily). Typical dose is 300mg/d (maximum 450mg).
  Wellbutrin is a novel aminoketone that is structurally similar to amphetamines. Dopamine uptake>Norepinephrine uptake. Formulary is short acting (75 and 100 mg tid), sustained release (100, 150, 200 mg b.i.d.) or extended release tablets ( 150 and 300 mg daily). Typical dose is 300mg/d (maximum 450mg).
• research: Two positive double blind placebo controlled trials; One positive study of Wellbutrin vs. Ritalin vs. placebo.
  Two positive double blind placebo controlled trials; One positive study of Wellbutrin vs. Ritalin vs. placebo.
• Trazodone: Sedative effect; efficacy for tics and bulimia await further studies and replication. Side effects: priapism, orthostatic hypotension
  Sedative effect; efficacy for tics and bulimia await further studies and replication. Side effects: priapism, orthostatic hypotension
• Nefazodone (Serzone), Mirtazapine (Remeron): Open label studies in PTSD and insomnia await further studies and replication. Side effects: sedation, weight gain, hypomania
  Open label studies in PTSD and insomnia await further studies and replication. Side effects: sedation, weight gain, hypomania
• Venlafaxine (Effexor): Open label study in ADHD. Used for depression and GAD in adults.
  Open label study in ADHD. Used for depression and GAD in adults.
• Seizures: Four times that of other antidepressants; 10 times at doses >=450 mg/day. Increased risk if: History of seizures, head trauma, CNS tumor or other organic brain disease Alcohol or benzodiazepines withdrawal, Concomitant administration of other psychotropics (haldol, lithium) that affect the seizure level, Eating disorders.
  Four times that of other antidepressants; 10 times at doses >=450 mg/day. Increased risk if: History of seizures, head trauma, CNS tumor or other organic brain disease Alcohol or benzodiazepines withdrawal, Concomitant administration of other psychotropics (haldol, lithium) that affect the seizure level, Eating disorders.
• Effectiveness for ADHD medications well-documented: By 1996, there were 161 RCTs published: 5 preschool, 150 school aged, 7 adolescent, and 9 adult. Studies consistently noted a positive response for core ADHD symptoms and showed improvement in 65% to 75% of patients.
  By 1996, there were 161 RCTs published: 5 preschool, 150 school aged, 7 adolescent, and 9 adult. Studies consistently noted a positive response for core ADHD symptoms and showed improvement in 65% to 75% of patients.
• Combination treatment and medication alone: The NIMH Multimodal Treatment Study of Children with ADHD (MTA; 1999) picked 18 nationally recognized authorities at 6 university medical centers to evaluate the leading treatments for ADHD. The study included 600 children who were randomized into 1 of 4 treatment groups: Medication alone, Psychosocial/behavioral treatment alone, combination of medication and behavior or routine community care. The study found that combination treatment and medication alone are superior to intensive behavioral treatments and routine community treatments in reducing ADHD symptoms. Follow up study showed benefits at 24 months as well as that combination treatment was not superior to medication alone except for targeting other areas. These areas included anxiety, oppositionality, parent-child relations, and social skills deficits.
  The NIMH Multimodal Treatment Study of Children with ADHD (MTA; 1999) picked 18 nationally recognized authorities at 6 university medical centers to evaluate the leading treatments for ADHD. The study included 600 children who were randomized into 1 of 4 treatment groups: Medication alone, Psychosocial/behavioral treatment alone, combination of medication and behavior or routine community care. The study found that combination treatment and medication alone are superior to intensive behavioral treatments and routine community treatments in reducing ADHD symptoms. Follow up study showed benefits at 24 months as well as that combination treatment was not superior to medication alone except for targeting other areas. These areas included anxiety, oppositionality, parent-child relations, and social skills deficits.
• Dexmethylphenidate: New drug which is formulated by isolating the active d-isomer of methylphenidate (Ritalin). This is believed to reduce side effects. Focalin was approved by the FDA in 2005 for use with ADHD in children 6 years and older and adults.
  New drug which is formulated by isolating the active d-isomer of methylphenidate (Ritalin). This is believed to reduce side effects. Focalin was approved by the FDA in 2005 for use with ADHD in children 6 years and older and adults.
• Atomoxetine: "FDA Alert (09/05): Suicidal Thinking in Children and Adolescents The Food and Drug Administration (FDA) directed Eli Lilly (Lilly) to revise the labeling for Strattera to include a boxed warning and additional warning statements regarding an increased risk of suicidal thinking in children and adolescents being treated with this drug. Strattera is currently approved in the United States to treat ADHD in children, adolescents, and adults. Strattera has not been studied in children under 6 years of age." This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.
  "FDA Alert (09/05): Suicidal Thinking in Children and Adolescents The Food and Drug Administration (FDA) directed Eli Lilly (Lilly) to revise the labeling for Strattera to include a boxed warning and additional warning statements regarding an increased risk of suicidal thinking in children and adolescents being treated with this drug. Strattera is currently approved in the United States to treat ADHD in children, adolescents, and adults. Strattera has not been studied in children under 6 years of age." This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.
• Stimulant-associated height deficits: "Catch up period" unrelated to weight deficit or stimulant treatment and no effect on pubertal timing.
  "Catch up period" unrelated to weight deficit or stimulant treatment and no effect on pubertal timing.
• No clear evidence linking Adderall and sudden death: In February 2005 Health Canada suspended the market authorization of Adderall XR as a result of a review of safety information which indicated there were 20 international reports of sudden death. Twelve of these deaths occurred in children but none of the deaths appeared to be linked to overdose, misuse or abuse. Both AACAP and the FDA agree that sufficient data are lacking at this time to infer causality between the medication and the sudden unexplained deaths. AACAP recommends that physicians continue practices as before without immediate changes and describe and discuss with parents/guardians and with the patient the risks and benefits of any treatment. However, physicians should refrain from prescribing Adderall XR for children with a family history of sudden cardiac death, individual medical history of cardiac structural problems or abnormal EKG.
  In February 2005 Health Canada suspended the market authorization of Adderall XR as a result of a review of safety information which indicated there were 20 international reports of sudden death. Twelve of these deaths occurred in children but none of the deaths appeared to be linked to overdose, misuse or abuse. Both AACAP and the FDA agree that sufficient data are lacking at this time to infer causality between the medication and the sudden unexplained deaths. AACAP recommends that physicians continue practices as before without immediate changes and describe and discuss with parents/guardians and with the patient the risks and benefits of any treatment. However, physicians should refrain from prescribing Adderall XR for children with a family history of sudden cardiac death, individual medical history of cardiac structural problems or abnormal EKG.
• Strattera: Strattera provides 24-hour coverage with daily administration. It may take 3-6 weeks for effect. Side effects include: abdominal discomfort (up to 30%), decreased appetite, sleep disturbance, lethargy, headache, dizziness, and possible liver problems. New labeling has a bolded warning about the potential for severe liver injury following two reports in patients who had been treated with Strattera for several months, both of whom recovered.
  Strattera provides 24-hour coverage with daily administration. It may take 3-6 weeks for effect. Side effects include: abdominal discomfort (up to 30%), decreased appetite, sleep disturbance, lethargy, headache, dizziness, and possible liver problems. New labeling has a bolded warning about the potential for severe liver injury following two reports in patients who had been treated with Strattera for several months, both of whom recovered.
• Buspirone: Not FDA approved for use in children.
  Not FDA approved for use in children.
• Clonidine and Combined Clonidine + Methylphenidate improved both tics and ADHD symptoms: Adverse Reaction Concern: Four children died suddenly on both medicines. The proposed mechanism had to do with opposing hemodynamic effects of the two drugs but the causality is uninterpretable.
  Adverse Reaction Concern: Four children died suddenly on both medicines. The proposed mechanism had to do with opposing hemodynamic effects of the two drugs but the causality is uninterpretable.
• Lithium is FDA approved: Non-FDA indications: Depression augmentation therapy, Decrease aggressive behavior in conduct disorder, Decrease aggressive behavior in children with mental retardation.
  Non-FDA indications: Depression augmentation therapy, Decrease aggressive behavior in conduct disorder, Decrease aggressive behavior in children with mental retardation.
• Randomized controlled trials indicate generally positive effects: Positive study of Lithium vs. placebo in substance-abusing bipolar adolescents; Positive study of Lithium vs. Haldol vs. placebo for aggression in under-socialized aggressive conduct disorder (Replicated in a separate study by the same group; Contrasts one negative study); Three positive double-blind RCT from 1970s of Carbamazepine vs. placebo for behavioral problems and high activity levels; Negative double-blind RCT of Carbamazepine vs. placebo in hospitalized aggressive children with conduct disorder
  Positive study of Lithium vs. placebo in substance-abusing bipolar adolescents; Positive study of Lithium vs. Haldol vs. placebo for aggression in under-socialized aggressive conduct disorder (Replicated in a separate study by the same group; Contrasts one negative study); Three positive double-blind RCT from 1970s of Carbamazepine vs. placebo for behavioral problems and high activity levels; Negative double-blind RCT of Carbamazepine vs. placebo in hospitalized aggressive children with conduct disorder
• new anticonvulsants: Gabapentin (Neurontin), Lamotrigine(Lamictal), Topiramate(Topamax)
  Gabapentin (Neurontin), Lamotrigine(Lamictal), Topiramate(Topamax)
• Lithium: Close monitoring indicated for renal function, thyroid, pregnancy test, calcium, ECG, CBC
  Close monitoring indicated for renal function, thyroid, pregnancy test, calcium, ECG, CBC
• haloperidol: FDA approved for children age 3 and older.
  FDA approved for children age 3 and older.
• pimozide: FDA approved for children age12 and older for Tourette's syndrome. Data for age 2 and older indicate similar safety profile
  FDA approved for children age12 and older for Tourette's syndrome. Data for age 2 and older indicate similar safety profile
• thioridazine: FDA approved for children age 2 and older.
  FDA approved for children age 2 and older.
• Baseline and follow-up physical evaluation: Abnormal movements 1) Weight, BMI, Heart Rate & Blood Pressure 2) Gynecomastia in boys; Abnormal menses in girls 3) Sexual dysfunction in adolescents 4) Fundoscopic exam 5) Fasting lipids, insulin, glucose 6) EKG
  Abnormal movements 1) Weight, BMI, Heart Rate & Blood Pressure 2) Gynecomastia in boys; Abnormal menses in girls 3) Sexual dysfunction in adolescents 4) Fundoscopic exam 5) Fasting lipids, insulin, glucose 6) EKG
• "Extrapyramidal" Motor Effects: akinesia (Parkinsons-like symptoms), akathesia, dystonias, dyskinesias -- tardive dyskinesia may be permanent
  akinesia (Parkinsons-like symptoms), akathesia, dystonias, dyskinesias -- tardive dyskinesia may be permanent