Psychiatric drugs used in children

1. PEDIATRIC PSYCHOPHARMACOLOGY
PRESENTER – Dr. Sriram.R, PG MD Psychiatry
CHAIRPERSON – Dr. Arul Saravanan, Assistant Prof of Psychiatry

3. INTRODUCTION
 Pediatric Psychopharmacology refers to the study of
interaction of drugs with the body and its behavioral effects
in children [1]
 First reports of psychotropic drug use in adolescents in the
1930’s by Charles Bradley [2]

4. HISTORY OF PEDIATRIC PSYCHOPHARMACOLOGY
 1997- FDA Moderation Act gave incentives for pediatric
research on already adult-approved medications [3]
 2002- Best Pharmaceuticals for Children Act- an extensive
process for studying medications in pediatric populations [3]
 2003- Pediatric Research Equity Act authorized FDA to require
drug manufacturers to conduct pediatric studies [3]
 With these regulations  consumers and medical providers
have a fairly large database for using these psychotropic
medications in children

5. PHARMACOKINETICS:
 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

6. 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

7. CLASSIFICATION OF DRUGS
 Each class of drugs has a different way of functioning in the
body [4]:
• Stimulants
• Anti-depressants
• Anti-psychotics
• Mood Stabilizers/Anti-Convulsants
• Anxiolytics and Sedatives

8. STIMULANTS
 Centrally and peripherally enhance both dopaminergic and
noradrenergic transmission to improve cognitive and behavioral
functioning [2]
 Methylphenidate (Ritalin), Dextroamphetamine (Focalin),
Pemoline (Cylert), Amphetamine-dextroamphetamine
(Adderall)
 Are the most prescribed psychotropic agents
 Most commonly used with ADHD [5]
 Over 200 controlled studies have shown that stimulant
medications are safe and effective [2]

9. ANTI-DEPRESSANTS
 Act on central pre- and post-synaptic receptors  affect
neurotransmitter release and uptake (i.e. serotonin,
norepinephrine, dopamine) [2]
 4 main sub-classes: monoamine oxidase inhibitors (MAOIs),
tricyclic (TCAs), selective serotonin uptake inhibitors (SSRIs),
atypical anti-depressants
 Of these, SSRIs are the most frequently prescribed (i.e. Prozac,
Zoloft, Paxil)
 Mostly used for major depressive disorder, but also for: OCD,
insomnia, ADHD, anxiety disorders [4]

10. ANTI-PSYCHOTICS
 Effectively treat psychosis, including hallucinations, delusions,
bizarre behavior, severe agitation [4]
 Thought to be related to dopamine antagonist properties
 2 main classes: traditional and atypical
 Common anti-psychotics: Olanzapine (Zyprexa), Clozapine
(Clorzaril), Chlorpromazine (Thorazine)
 Mostly used for schizophrenia, but also for psychotic
depression, mania, autism spectrum disorders, severe
aggressive behaviors [15]

11. MOOD STABILIZERS/ANTI-CONVULSANTS
 Act through a variety of mechanisms affecting intracellular
processes- still being researched
 3 most commonly used: lithium, valproate, and
carbamazepine [2]
 Lithium is only FDA approved drug for pediatric bipolar
disorder [4]
 Also used to improve aggressive behavior and conduct disorder
 Valproate effectively treats mania in adults and possibly
children

12. Anxiolytics and Sedatives
 Relatively less evidence compared to the other categories
of medication, but still used with pediatric medications [2]
 Benzodiazepines have been used for anxiety (GAD) and
panic disorders [15]
 Buspirone, TCA’s, SSRIs, Beta Blockers, and α-2a agonists
[4]
 Need for more research with children, so not as frequently
used

13. Miscellaneous
 Atomoxetine (Strattera)- nonstimulant drug that was
approved for ADHD treatment [9]
 Thought to inhibit norepinephrine receptors
 Clonidine- α-adrenergic agonist used especially for tics and
sometimes ADHD and anxiety disorders [13]
 Reduces sympathetic outflow directly at the brain stem 
therapeutic
effects

14. DISORDERS IN CHILDREN
 ADHD
 Pediatric Bipolar
 Depression
 OCD
 Schizophrenia
 Anxiety
 Autism
 Anorexia
 Bulimia nervosa
 Obesity

15. ADHD
 ADHD is the most commonly diagnosed psychiatric disorder
of childhood [2]
 4.5 million children between 5-17 years of age have been
diagnosed with ADHD as of the end of 2006. [6]
• Children with ADHD can experience peer rejection,
impulsivity, disruptive behaviors, low self-esteem 
which can affect their daily life [7]
• If not treated, symptoms can persist into adulthood [2]
Medication has proven to be extremely
effective for treating ADHD

16.  Over 200 controlled studies have shown that
stimulant medication is safe and effective [2]
 Methylphenidate and atomoxetine have repeatedly
been found to decrease inattention and hyperactivity
[9]
 Stimulants for ADHD do not result in substance
abuse disorders and may actually have a protective
effect against development of substance abuse in
adolescence [8]
 Also protective factor for legal difficulties and poor
impulse control
 Concerns that stimulant medication may be
responsible for smaller brain structures  not well
supported [5]
ADHD

17.  Semrud-Clikeman et al. 2008 [7]
 Compared ADHD kids that have at least some
history of medication (current or past) to ADHD
kids that were never exposed to treatment
 ADHD children with some history of medication
performed significantly better in writing,
attention, executive functioning, verbal working
memory, and academics. They also had less
mood problems and aggressive behaviors.
 ADHD children that have been
medicated show better functioning
even when medicine has been
discontinued.
ADHD

18.  Pappadopulos et al. 2004 [11]
 When reviewing a decade of studies-
stimulant medication has been tested on over
6000 ADHD children  substantial evidence
showing stimulants are effective at treating
ADHD symptoms
ADHD
• Pelham et al. 2002 [12]
– Methylphenidate shown to reduce ADHD
treatments in children with normal and low IQ

19.  ADHD Attitudes [5]
 Parent
 Over 90% of parents challenged and were
skeptical of the doctor’s recommendation
of starting medication
 After 2 years- about 80% of parents
considered methylphenidate a safe and
effective drug
ADHD
• A few parents stopped the medication in between- but all of
them restarted treatment because of belief that child
performed better on medication
– Child:
• After 2 years on stimulant drugs- 86% of kids considered
methylphenidate safe and effective

20.  In the school settings- teachers and school
psychologists are working with medical doctors to
provide a multinodal treatment for ADHD children
[10]
 Medication combined with psychosocial interventions
show greatest decrease in symptoms
 75% of parents believe that the best treatment for
ADHD = methylphenidate + psychological support
 Behavioral interventions alone did not exert
improvement in academic performance, emotional
status, and overall functioning [13]
 American Academy of Pediatrics announced that
stimulant medication should be recommended to
improve outcomes in ADHD children [5]
ADHD

21. Effectiveness of
stimulants in
children 6 years
and older with
ADHD [14]
ADHD

22.  PBD children experience moods that alternate
between depression and mania episodes
 Early onset PBD often starts with depression episode
that switches to BD [2]
 Therefore hard to estimate PBD prevalence
 Children with PBD can be extremely harmful to
themselves, family, and society
Medication is critical with
almost all PBD cases
PEDIATRIC BIPOLAR DISORDER

23. PEDIATRIC BIPOLAR DISORDER
 Lithium- only FDA approved drug for treatment of PBD [15]
 Clinical Global Assessment Scale score of more than 65 was
achieved by 47% of kids receiving lithium versus 8% of kids on
the placebo [11]
 Findling et al. 2003 [17]
 Lithium + divalproex sodium (mood-stabilizer) treatment produced
significant improvements in various areas  47% subjects met
criteria for full remission after medication for 20 weeks

24. PEDIATRIC BIPOLAR DISORDER
 Kafantaris et al. 2001 [18]
 Lithium + Anti-psychotic treatment (Haloperidol)
showed improvement of symptoms for adolescents
with PBD
 Majority of patients showed reoccurrence of symptoms
once medication was discontinued
• Biederman et al. 2005 [21]
– When given Risperidone (anti-psychotic)- PBD patients
showed 70% response for manic symptoms and 35% for
ADHD symptoms.

25. PEDIATRIC BIPOLAR DISORDER
 Pavuluri et al. 2009 [16]
 Lamotrigine is an anti-convulsant commonly used for adult BD
 Controls glutamate release activates serotonin levels
 This study showed that kids on lamotrigine medication showed
significantly reduced depressive symptoms and controlled
aggression and irritability compared to the placebo group
 Previous adverse effect of benign rash only seen in 6% of
patients and was quickly treated with no long-term effects

26. PEDIATRIC BIPOLAR DISORDER
 PBD can be extremely severe if left untreated
 Certain researchers today consider it unethical to have a
placebo group for children with PBD  because
withholding treatment can have drastic long term effects
 Without medication- high risk for substance abuse, conduct
disorder, suicide, and other co-morbidities [21]
 Show symptoms of hallucinations, verbal and physical intrusion,
lack of self-control, delusional thinking, possibly assaultive, and
more [2]

27. DEPRESSION
 Increased rates of depression among kids: especially in
families dealing with divorce, abuse, neglect, bereavement
[3]
 Harvard Medical School study in 2006 found that childhood
depression is increasing by 23% a year
 Depression rates and suicide are strongly
correlated  suicide is the 6th leading cause of death
among children ages 5-14 [22]

28. DEPRESSION
 Fluoxetine (SSRI) has been shown to be superior to placebo
in many controlled studies. Emslie et al. 2002 [24] Tao et al.
2009 [26]
 Fluoxetine medication showed significantly improved results
compared to cognitive behavioral therapy alone [25]
 Only FDA approved drug for pediatric depression
 Tricyclic antidepressant (Anafranil) and paroxetine (Paxil)
have shown some promising results in the treatment of
pediatric depression
 More controlled studies is needed before these drugs can be
frequently distributed for treatment

29. OBSESSIVE COMPULSIVE DISORDER
 OCD in children obsessions, compulsions, persistent
thoughts, impulses, or images that are intrusive/inappropriate
[14]
 Causes anxiety & stress
 Repetitive behaviors are in response to obsession
• 1/3-1/4 of OCD patients had symptoms before the age of
15 [27]
• Symptoms can manifest similar to adult OCD but often
differently (i.e. temper tantrums, food restrictions,
decreased academic performance) [2]

30. OBSESSIVE COMPULSIVE DISORDER
 Of all childhood disorders- OCD has most evidence supporting
pharmacologic treatment & largest number of FDA approved
drugs [2]
 SSRIs fluoxetine (Prozac), fluvoxamine (Luvox), sertraline
(Zoloft) and clomipramine (Anafranil) are FDA approved for
treating childhood OCD (age 6 and up) [2]
 Geller et al. 2003 [28]
 Meta analysis of children with OCD showed significant difference
between children on medication and placebo
 Clomipramine was shown to be the most superior of the SSRIs [2]

31. OBSESSIVE COMPULSIVE DISORDER
 Wagner et al. 2003 [29]
 Sertaraline has been shown effective in long term trials
because of significant remission rates and improved functional
status in majority of patients
 Gellar et al. 2003 [28]
 Continued paroxetine treatment significantly reduces pediatric
OCD relapse rates compared to the placebo
 Is often comorbid with other disorders such as ADHD,
tics, anxiety disorders, and PBD [14]

32. SCHIZOPHRENIA
 Pediatric schizophrenia is serious disorder that affects cognition
and ability to relate socially with others  gross impairment of
reality [2]
 Symptoms include delusions, hallucinations, distortion,
disordered speech and communication, catatonic behavior,
intensity of emotions and exaggeration of behavioral control
[14]
 These children are significantly delayed in their school
functioning, relationships, and self care. Again, without
medication- can be extremely dangerous to themselves and
society.

33. SCHIZOPHRENIA
 Sikich et al. 2004 [30]
 Schizophrenic children and adolescents between 8-19 years of age
show significant improvement when taking either risperidone,
olazapine, and haloperiodol medication
 Sikich et al. 2008 [20]
 First and second generation atypical antipsychotics (molindone,
olanzapine and risperidone) have been shown to significantly decrease
pediatric schizophrenia symptoms
 Kranzler et al. 2005 [31]
 Schizophrenic children can often be extremely aggressive
 Clozapine treatment showed significant clinical improvement for
severely aggressive children

34. SCHIZOPHRENIA
 Psychotherapy alone has not been proven to be
effective for treating pediatric schizophrenia
 Adjunctive psychosocial treatments (psychoeducation,
behaviorally based therapy, cognitive-behavioral
therapy) improves symptoms and reduces relapse
rates [32]
• If the disorder is at an advanced stage- constant
hallucinations and bizarre ideation can take over the child’s
life without medication

35. ANXIETY DISORDERS
 One of the most commonly diagnosed psychiatric disorders
affecting populations in U.S. and Europe [14]
 Includes separation anxiety, panic disorder, social phobia, specific
phobias, and generalized anxiety
 Not only distress to thought of threat, but also cognitive feelings
of losing control, unwelcome or intrusive thoughts, inattention,
insomnia, and perceptual disturbances.
 Affects youth more than adults
because anxiety affects normal
physical and mental development

36. ANXIETY DISORDERS
 Due to a lack of current research, there are no FDA
approved drugs for the treatment of pediatric
anxiety disorders [2]
 But numerous medications have shown promising
results:
 SSRIs: such as Fluoxentine have shown notable
symptom reduction with minimal side effects [10]
 Benzodiazepines: such as Clonazepam is useful in
short-term treatment (i.e. used to ensure child attends
school) [2]
 α-2a Agonists: help with symptoms
of hyperautonomic arousal (i.e. palpitations)
 Tricyclic antidepressants [14]

37. OTHER DISORDERS
 There are several studies show evidence of psychotropic
medication decreasing symptoms in other disorders:
 Autism [2]
 SSRIs, anti-psychotic (haloperidol, thioridazine), α-2a agonists,
anticonvulsants, stimulants
 Anorexia nervosa [33]
 Atypical antipsychotics (olanzapine), appetite enhancers, mood stabilizers
 Bulimia nervosa [33]
 Anti-depressants, Tri-cyclic anti-depressants, SSRIs (fluoxentine)
 Obesity [33]
 Anti-depressants, appetite suppressants

38. DRUG DOSAGES AT A GLANCE

53. TERATOGENIC RISKS OF PSYCHOTROPICS

54.  Category A - Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in
the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
 Category B - Animal reproduction studies have failed to demonstrate a risk to the fetus and there
are no adequate and well-controlled studies in pregnant women.
 Category C - Animal reproduction studies have shown an adverse effect on the fetus and there
are no adequate and well-controlled studies in humans, but potential benefits may warrant use of
the drug in pregnant women despite potential risks.
 Category D - There is positive evidence of human fetal risk based on adverse reaction data from
investigational or marketing experience or studies in humans, but potential benefits may warrant
use of the drug in pregnant women despite potential risks.
 Category X - Studies in animals or humans have demonstrated fetal abnormalities and/or there is
positive evidence of human fetal risk based on adverse reaction data from investigational or
marketing experience, and the risks involved in use of the drug in pregnant women clearly
outweigh potential benefits.

57. CLINICAL MONITORING OF PSYCHOTROPICS IN
CHILDREN

60. REFERENCES
1) Orkin, B. G. (2002). The use of atypical antipsychotic agents for nonpsychotic disorders in children and adolescents. Doctoral dissertation, ProQuest Information and Learning
Company, Ann Arbor, MI.
2) Cheng, K., & Myers, K. M. (2005). Child and adolescent psychiatry: The essentials. Baltimore: Lippincott Williams & Wilkens.
3) Emslie, G. J. (2009). Understanding Placebo Response in Pediatric Depression Trials. American Journal of Psychiatry, 166(1), 1-3.
4) Brown, R. T., & Sammons, M. T. (2002). Pediatric psychopharmacology: A review of new developments and recent research. Professional psychology, research and practice,
33(2), 135-147.
5) Berger, I., Dor, T., Nevo, Y., & Goldzweig, G. (2008). Attitudes Toward Attention-Deficit Hyperactivity Disorder (ADHD) Treatment: Parents' and Children's Perspectives.
Journal of Child Neurology, 23(9), 1036-1042.
6) (2009). Retrieved April 14, 2009, http://www.cdc.gov/
7) Semrud-Clikeman, M., Pliszka, S., & Liotti, M. (2008). Executive Functioning in Children With Attention-Deficit/Hyperactivity Disorder: Combined Type With and Without a
Stimulant Medication History. Neuropsychology, 22(3), 329-340.
8) Wilens, T. E., Faraone, S. V., Biederman, J., & Gunawardene, S. (2003). Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse.
Pediatrics, 111(1), 179-185.
9) Spencer, T., Heilgenstein, J. H., Biederman, J., Faries, D. E., Kratochvil, C. J., Conners, K., et al. (2002). Results from 2 proof-of-concept, placebo-controlled studies of
Atomoxetine in children with attention-deficit/hyperactivity disorder. The Journal of Clinical Psychiatry, 63(12), 1140-1147.
10) Abrams, L., Flood, J., & Phelps, L. (2006). Psychopharmacology in the schools. Psychopharmacology in the schools, 43(4), 493-501.
11) Pappadopulos, E. A., Guelzow, T. B., Wong, C., Ortega, M., & Jensen, P. S. (2004). A review of the growing evidence base for pediatric psychopharmacology . Child and
Adolescent Psychiatric Clinics of North America, 13(4), 817-855.
12) Pelham, W. E., Hoza, B., Pillow, D. R., Gnagy, E. M., Kipp, H. L., Greiner, A. R., et al. (2002). Effects of methylphenidate and expectancy on children with ADHD: behavior,
academic performance, and attributions in a summer treatment program and regular classroom settings. Journal of Consulting and Clinical Psychology, 70(2), 320-325.
13) Abikoff, H., Hechtman, L., Klein, R., Gallagher, R., Fleiss, K., Ectovitch, J., et al. (2004). Social Functioning in Children With ADHD Treated With Long-Term Methylphenidate
and Multimodal Psychosocial Treatment. Journal of the American Academy of Child & Adolescent Psychiatry, 43(7), 820-829.
14) Vitiello, B., Masi, G., & Marazziti, D. (2006). Handbook of child and adolescent psychopharmacology (). New York: Informa HealthCare.
15) Ryan, N. D. (2003). Medication treatment for depression in children and adolescents. CNS Spectrums, 8(4), 283-287.
16) Pavuluri, M. N., Henry, D. B., Moss, M., Mohammed, T., Carbay, J. A., & Sweeney, J. (2009). Effectiveness of Lamotrigine in Maintaining Symptom Control in Pediatric
Bipolar Disorder. Journal of Child and Adolescent Psychopharmacology, 19(1), 75-82.

61. 17) Findling, R. L., McNamara, N. K., Stansbrey, R., Gracious, B. L., Whipkey, R. E., Demeter, C., et al. (2006). Combination lithium and divalproex sodium in
pediatric bipolarity. Journal of the American Academy of Child and Adolescent Psychiatry, 45(2), 142-146.
18) Kafantaris, V., Dicker, R., Coletti, D. J., & Kane, J. M. (2001). Adjunctive Antipsychotic Treatment Is Necessary for Adolescents with Psychotic Mania. Journal of
Child and Adolescent Psychopharmacology, 11(4), 409-413.
19) Biederman, J. (2005). Attention-deficit/hyperactivity disorder: a selective overview. Biological Psychiatry, 57(11), 1215-1220.
20) Sikich, L., Frazier, J., McClellan, J., Findling, R., Vitiello, B., Ritz, L., et al. (2008). Double-Blind Comparison of First- and Second-Generation Antipsychotics in
Early-Onset Schizophrenia and Schizo-affective Disorder: Findings From the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study.
American Journal of Psychiatry, 165, 1369-1372.
21) Wilens, T., Biederman, J., Kwon, A., Ditterline, J., Forkner, P., Moore, H., et al. (2004). Risk of Substance Use Disorders in Adolescents With Bipolar Disorder.
Journal of the American Academy of Child & Adolescent Psychiatry, 43(11), 1380-1386.
22) (2009). Retrieved 14 Apr. 2009, http://www.about-teen-depression.com/depression-statistics.html
23) (2008). Retrieved 14 Apr. 2009, http://www.raisinganoptimisticchild.com/statistics.html
24) Emslie, G. J., Heiligenstein, J., Wagner, K. D., Hoog, S., & Ernest, S. E. (2002). Fluoxetine for Acute Treatment of Depression in Children and Adolescents: A
Placebo-Controlled, Randomized Clinical Trial. Journal of the American Academy of Child & Adolescent Psychiatry, 41(10), 1205-1215.
25) TADS Team (2004) The Treatment for Adolescents with Depression Study (TADS): short-term effectiveness and safety outcomes. JAMA 292:807–820
26) Tao, R., Emslie, G., Mayes, T., Nakonezny, P., Kennard, B., & Hughes, C. (2009). Early prediction of acute antidepressant treatment response and remission in
pediatric major depressive disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 48(1), 71-78.
27) Oner, O., & Oner, P. (2008). Psychopharmacology of pediatric obsessive compulsive disorder: three case reports. Journal of Psychopharmacology, 22(7), 809-
811.
28) Geller, D. A., Biederman, J., Stewart, E., Mullin, B., Martin, B., & Spencer, T. (2003). Which SSRI? A Meta-Analysis of Pharmacotherapy Trials in Pediatric
Obsessive-Compulsive Disorder . American Journal of Psychiatry, 160, 1919-1928.
29) Wagner, K., Ambrosini, P., Rynn, M., Wohlberg, C., Yang, R., Greenbaum, M., et al. (2003). Efficacy of Sertraline in the Treatment of Children and Adolescents
With Major Depressive Disorder . The Journal of the American Medical Association, 290(8), 1033-1041.
30) Sikich, L., Hamer, R. M., Bashford, R. A., Sheitman, B. B., & Lieberman, J. A. (2004). A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth:
A double-blind, randomized, 8-week trial. Neuropsychopharmacology, 29(1), 133-145
31) Kranzler, H., Roofeh, D., Gerbino-Rosen, G., Dombrowski, C., McMeniman, C., Dethomas, C., et al. (2005). Clozapine: Its impact on aggressive behavior
among children and adolescents with schizophrenia. Journal of the American Academy of Child and Adolescent Psychiatry, 44(1), 55-63.
32) Rector, N. A., & Beck, A. T. (2001). Cognitive Behavioral Therapy for Schizophrenia: An Empirical Review. The Journal of Nervous and Mental Disease, 189(5),
278-287.
33) Powers, P. S., & Bruty, H. (2009). Pharmacotherapy for Eating Disorders and Obesity. Clinics , 18(1), 175-187.
REFERENCES

62. THANK YOU