Pediatric Psychopharmacology

The Facts and Why it Can Save Our Kids

Armeta DastyarPriya Mathews

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]

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

What’s the Controversy About?

• Supporters claim that the use of psychotropic drugs can help manage pediatric disorders where behavioral or psychosocial interventions alone cannot. Also, it is important to prevent these children from harming themselves or others.

• Opponents claim that many of these drugs have not been extensively tested for children and that long term effects are still unknown. They believe that we are overmedicating our children.

Evaluations Required• Are kids simply being put on

numerous drugs without a second thought? [4]

• Extensive physical and psychiatric evaluations in a variety of settings are required:– Physical examination– Structured interview– Behavioral rating scales– Direct observations of behavior– Standardized measures of performance

Different Classes of Drugs• Doctors strive to find the safest and most

effective medication for every individual child.• 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

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]

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]

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]

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

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) andpanic disorders [15]

• Buspirone, TCA’s, SSRIs, Beta Blockers, and α-2a agonists [4]

• Need for more research with children, so not as frequently used

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

Disorders that All Show Support for Pediatric Psychopharmacology

• ADHD• Pediatric Bipolar• Depression• OCD• Schizophrenia• Anxiety• Autism• Anorexia• Bulimia nervosa• Obesity

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]

CDC, 2007

• 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

• 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

• 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

• 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

• 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

• 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

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

ADHD

ADHD

Video Clip

• 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

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

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.

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

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]

Pediatric Bipolar Disorder

Video Clip

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 6th leading cause of death

among children ages 5-14 [22]

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

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]

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]

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]

Obsessive Compulsive Disorder• Case 1 [27] :

– 4 year old with symptoms: severe anxiety, lack of appetite, frequent crying, dysphoric mood and obsession with sexual contact diagnosed with OCD

– Began medication (Sertaline) because of severity of symptoms and had to double the dose due to lack of response

– Risperidone added to control side effects of Sertaline (i.e. hyperactivity, impulsivity)

– Symptoms completely resolved after 9 months of treatment

• Case 2 [27] :– 5 year old with symptoms: swearing to God, excessive handwashing

and rituals diagnosed with OCD– Prescribed Sertraline and after 2 months – patient was symptom free

and has been ever since

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.

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

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

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

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]

Anxiety DisordersCase study [2] :

– 8 year old who had symptoms of: poor academic performance, followed mother everywhere, cried in school everyday because hated parting with mother, would become physically sick in school until mother came, and symptoms lessened on weekends

– Diagnosed with SAD prescribed sertraline and intensive behavioral therapy

– After just one month- the child had already improved his symptoms (began attending schools without any argument, reduced physical sickness in school)

– Eventually tapered off medication after remission

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

Opposition to Pediatric PsychopharmacologyReasons Against Pediatric Meds But….

Drug addiction No significant evidence showing this is true certain medications act as protective factors against later substance abuse and criminal problems

Drug overdose If properly monitored and regulated by family and doctors should not be an issue

Suicide Yes this is a possible risk- but how many suicides are we preventing with medication? Also if suicide is a high risk- then clozapine and lithium have been shown to be effective treatments [15]

Weight gain & other side effects Possibility- but drug dosage can be adjusted to minimize risks. Also, what medications don’t come with possible side-effects?

Not enough research Pediatric psychopharmacology is a rapidly growing field that is repeatedly testing medications. Also FDA works extensively before approving any medication, and will continue to come out with approvals for more drugs to help save children

Over-prescribed If done properly- before prescribing medication there should be an overall extensive evaluation of the child in a variety of settings. The problem of over-prescribing is due to lack of monitoring and standardized system , rather than the drug itself.

Parents aren’t given a choice As mentioned before- majority of parents consult other medical and non-medical advisors before giving their children medication.

Conclusions

• Clearly there is a substantial amount of evidence that supports the use of pediatric psychopharmacology

• Of course, adjunctive therapy can definitely help…but the unique effect of medication cannot be ignored

• These children can be extremely sick, and medication is the only way for them and their family to have a chance of a normal life

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