Pediatric Psychopharmacology
AACAP PRESIDENTIAL INSTITUTE ON PRACTICAL PEDIATRIC PSYCHOPHARMACOLOGY
Report compiled by Vishal Madaan, M.D., Department of Psychiatry, Creighton University/University of Nebraska Medical Center, Omaha, NE
May 4, 2008
The major objective of this institute is to provide practical information to clinicians on the use of psychotropic medications in the treatment of children and adolescents in their practice.
A. EVIDENCE-BASED PHARMACOTHERAPY FOR ADHD
Laurence L. Greenhill, M.D.
ADHD is a common neuropsychiatric disorder, and one primary care clinicians are often called upon to manage pharmacologically. This presentation provided information regarding evidence based pharmacotherapy for management of ADHD. Various forms of stimulant and nonstimulant preparations were reviewed along with efficacy, tolerability and short-and long-term safety data. Recent preschool ADHD study (PATS) had looked at the use of immediate-release methylphenidate which was found to be efficacious and safe in the preschoolers. The clinicians need to be careful in making a diagnosis of ADHD, especially looking at anxiety disorders and learning disabilities as common differential diagnoses. Recent American Heart Association guidelines have recommended getting a baseline EKG before starting treatment with any of the medications used to treat ADHD. The implications of this are still being reviewed by the AACAP and APA, especially given the limited availability of pediatric cardiologists in various parts of the country.
B. TEN THINGS A PRIMARY CARE CLINICIAN NEEDS TO KNOW ABOUT BIPOLAR, SCHIZOPHRENIA, AUTISM AND AGGRESSION IN CHILDREN & ADOLESCENTS
Adelaide S. Robb, M.D.
This presentation was aimed at teaching primary care physicians and general psychiatrists the salient aspects about diagnosis, treatment and clinical management of children with bipolar disorder, schizophrenia, autism and aggressive behavior.
As more children with these disorders are being treated in the community, it is important for clinicians to recognize these disorders and be able to manage them with psychotropic medications. While discussing pediatric bipolar disorder, she mentioned the key presenting symptoms of the disorder, especially highlighting that children with a manic presentation may be more likely to have psychotic symptoms and that a family history of bipolar disorder may be especially helpful in making a diagnosis. Similarly, a family history of response to mood stabilizing medication may be the best predictor of response in the pediatric age group.
The clinical features and diagnostic criteria for autism were reviewed in the presentation. Most severe cases with autism present early (18 months-3 years) with a failure to acquire language milestones, poor social interactions, repetitive behaviors and also extreme temper tantrums. Apart from Applied behavioral analysis, pharmacotherapeutic approaches that are used include the use of atypical antipsychotics especially risperidone for associated aggression, SSRIs or SNRIs for treatment of comorbid anxiety and depression, use of stimulants and atomoxetine for comorbid ADHD, and anticonvulsants for treatment of aggression, mood symptoms and seizure disorder.
The following rating scales can be used by clinicians for assessment of symptoms in manic episodes, psychotic episodes, aggression and autism and also for monitoring response to treatment:
1. Manic episode: Young Mania Rating scale (YMRS)
2. Psychotic episode: Brief Psychotic Rating scale for children (BPRS-C) and Positive and Negative Symptom scale (PANSS)
3. Autism: Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS)
4. Aggression: Overt aggression scale (OAS) and Aberrant behavior checklist (ABC)
The FDA has approved the use of lithium for bipolar disorder (age 12 years and older), risperidone for irritability in autism (5-16 years), bipolar mixed and manic episodes (10-17 years) and schizophrenia (13-17 years), and aripiprazole for bipolar mixed and manic episodes (10-17 years) and schizophrenia (13-17 years). Adverse effects of various mood stabilizers and second generation antipsychotics were carefully reviewed.
To conclude, Dr. Robb mentioned the following ten pearls of clinical wisdom that are beneficial in everyday clinical psychiatry in children and adolescents:
1) Aggression is only a symptom and is not a diagnosis per se. The clinician needs to identify the underlying cause for aggression.
2) Autism presents very early (usually 18 months-3 years) in a child’s lifespan; the clinician should be vigilant for early signs especially deficits in communication.
3) A bipolar manic episode may present with irritability or silly or reckless behavior in child, age 6 or older.
4) Schizophrenia in childhood may present with present with positive symptoms, but is more commonly associated with negative symptoms such as social withdrawal, or with deteriorating academic performance at school.
5) Adverse effects from lithium use in childhood may include renal problems or hypothyroidism; an increase in acne is also more commonly observed in the pediatric population. Lithium use requires regular monitoring of serum lithium levels, renal function tests and TSH assessment.
6) Anticonvulsant use in children may alter their use of oral contraceptives, and may also result in hepatic, hematological and endocrine adverse effects.
7) Clozapine is the treatment of last resort in children with schizophrenia because of associated serious adverse effects including agranulocytosis, seizures and myocarditis. Clozapine is the only antipsychotic that has been associated with decrease in suicidality.
8) Antipsychotics, especially atypicals, are being commonly used for almost all of the conditions discussed in this talk.
9) Use of most of the psychotropic medications in childhood is not FDA approved. However, lack of FDA approval doesn’t necessarily indicate that the medication is not efficacious in treating childhood psychiatric disorders.
10) The clinician should gradually add one to two psychotropic medications from each group to their armamentarium and should become familiar and experienced with their use before adding more.
C. MANAGEMENT OF PEDIATRIC DEPRESSION
Jefferson B. Prince, M.D.
Childhood depression is a common disorder, with significant morbidity and mortality, but is also one that is easily identifiable and treatable. Common clinical features include irritability and dysphoria, feeling “bored”, social withdrawal, abnormal sleep patterns, fatigue, “mood reactivity”, feelings of blame or guilt and ideas of hopelessness and worthlessness, and suicidal preoccupations. Depression may be more common in females and ethnic minorities. Recent studies have indicated that approximately 16% of females and 10% of males plan for suicide, while 10% of females and 6% of males attempt suicide. Suicide remains the 3rd leading cause of death in the 15-19 year age group. Common comorbid disorders associated with depression include ADHD, ODD and anxiety disorders. In an interesting 10 year follow up of prepubertal depression, 49% subjects switched to bipolar disorder. Also, in adolescent depression, 20% switch to bipolar disorder in 1-4 years. A commonly used rating scale for assessement of childhood depression is Childhood Depression Rating Scale (CDRS).
The high points in treatment of pediatric depression include:
1) Education is the foundation of successful treatment. The parents and child should be educated regarding clinical features of depression, course and prognosis and treatement options. They should be advised to remove all guns from the house. They should identify available supports and how to access them. They should also agree on a treatment and a safety plan.
2) Wellness/Lifestyle changes: Changes in diet, exercise, sleep patterns, decreasing or stopping substance abuse, participation in school activities, may all be activities that are helpful in improving symptoms of depression.
3) CBT and antidepressant use: Treatment of Adolescents with Depression study (TADS) had shown the best efficacy data with combination treatment at 12 weeks; however, long term 36 week data from the study showed that all three active arms of treatment including fluoxetine, CBT and combination were efficacious with no major differences among the three. Fluoxetine still remains the only FDA approved antidepressant for the pediatric age group. Treatment with an antidepressant should at least last for 6-9 months after attainment of euthymia, but may be longer for recurrent or sever episodes.
To conclude, pediatric depression is a common disorder that is identifiable and treatable. CBT, Fluoxetine and their combination are efficacious approaches for treatment of childhood depression.
D. PEDIATRIC ANXIETY DISORDERS
John T. Walkup, M.D.
Anxiety disorders are common in children and adolescents, but are also commonly overlooked. Clinicians need to be vigilant in looking for anxiety disorders and should not presume that the child will grow out of an anxiety disorder.
Rating scales that can be clinically useful for assessment of anxiety disorders include:
1. Multidimensional Anxiety scale for children (MASC)
2. Screen for Childhood Anxiety related emotional disorder scale (SCARED)
3. Achenbach’s Childhood behavior checklist (CBCL)
Here, we look at some of the key points in the discussion regarding each of the anxiety disorders:
Social anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia: Recent studies have found that social anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia are highly comorbid among each other. The children with SAD have concerns regarding separation from home and something bad happening to their parents or themselves. They may present with physical aches and pains and may have decreased sleep/may want to sleep with parents. These children may also present with numerous accommodations being made by parents e.g. homeschooling instead of regular school. Selective mutism may be considered a more severe form of SAD largely with an inability to speak in social situations. The common symptoms and signs to look for when diagnosing separation anxiety disorder include:
1) Physical complaints: Include fullness of throat, shortness of breath, stomachaches, headaches, chest pain, ringing in ears, dizziness and other. A couple of key points here include that most of these children get decreased sleep in PM and are sick in AM. Also, after school, they feel tired, tense and exhausted.
2) Problems with falling asleep, with repeated visits to parents’ room
3) May overeat or undereat
4) Avoidance of outside and decreased interpersonal interactions outside of house
5) Increased needs for reassurance
6) Explosive outbursts
7) Poor academic performance at school
Treatment options that have been tried include use of imipramine, clomipramine, clonazepam, along with efforts to send the child to school consistently.
Specific phobias: Seventy percent of children with specific phobias may have another anxiety disorder. The specific phobia may be situational or environmental in nature.
Obsessive compulsive disorder: Symptoms such as ordering, repetitiveness and checking may be associated with more comorbidities as compared to contamination symptoms that have least comorbidities. The treatments of choice include cognitive behavioral therapy, use of serotonin reuptake inhibitors including clomipramine (FDA approved starting age 10), fluvoxamine (approved starting age 8), fluoxetine (approved starting age 6) and others. Results from the pediatric OCD treatment study (POTS) have suggested that combination of CBT+Sertraline > sertraline alone= CBT alone > Pill placebo in treatment of pediatric OCD. Newer research on deep brain stimulation and neurosurgery as treatment options for OCD are underway.
Acute Stress Disorder is characterized by the presence of a life threatening event followed by the occurrence of re-experiencing, avoidance and increased arousal symptoms. This is usually time limited but can result in enduring symptoms in the form of PTSD. The risk factors that are associated with development of enduring symptoms include the presence of a pre-existing psychiatric disorder, proximity to the event and post-traumatic environment.
Recent research: A large scale NIMH funded trial, Child/adolescent Anxiety Multimodal study (CAMS) was carried out to determine the modality that is most successful to treat patients with SAD, GAD and social phobia. A comparison among combination of CBT + pharmacotherapy, pharmacotherapy alone, CBT alone and placebo was made in a total of 488 subjects. The subjects underwent 12 weeks of acute phase treatment followed by 6 month follow up. The results of the study are still awaited.
Finally, to conclude, anxiety disorders are extremely common, they are easy to miss and anxiety disorders respond to treatment exceedingly well. Research clearly demonstrates that treatment of anxiety disorders can significantly lower distress and improve functioning.
E. PEDIATRIC PSYCHOPHARMACOLOGY CASE PRESENTATIONS: PRACTICAL APPLICATIONS
Christopher Jon Kratochvil, M.D.
This session involved a presentation of clinical vignettes to the panel, followed by an interactive format with discussion of patient management by faculty and attendees. This presentation allowed the attendee to apply infor¬mation from the didactic presentations as well as clinical experi¬ence to the patient vignettes, providing an opportunity for a practical application of the data presented earlier in the institute. Some of the vignettes presented covered key topics such as treating a preschooler with ADHD, management of weight loss in patients with stimulants, long term growth issues in treatment of ADHD, treatment of gastrointestinal symptoms in patients on atomoxetine, and others. This session provided a practice opportunity to the clinicians to translate the knowledge derived from the presentations into their clinical practice.