# Presentation: 156354

## American Academy of PediatricsCommittee on Children with DisabilitiesPerspective on

*The Use of Antimuscarinics for the Control of Drooling in Children with Cerebral Palsy and Other Neurologic Deficits*

## The Big Picture

- We strongly support meaningful studies of all medications used in children, particularly vulnerable children with special needs
- Indications for children without special needs are ***not*** always applicable to children with disabilities

## In general, studies must address

- Dosing
- Delivery and formulation
- Pharmacokinetics
- Adverse effects, which must be presented in a developmental context.
- In children with developmental disabilities a paradigm shift must be made.

## Studies must also address

- Subgroup differential response
- Issues of polypharmacy
- How to make choices between medications in same class
- How to make choices between different therapies
- Multiple ethical issues

## This topic presents an unusual 	and complex 		set of issues

- Efficacy of these agents in reducing saliva production and drooling is not the major issue - this is well documented.
- A Zen like balance must exist between inhibition of saliva production and adverse effects.
- The literature largely lacks scientific rigor and provides little comparison between intervention efficacy.
- These children need complex pathological and adaptive function assessment. There are many etiologies and mechanisms which create subgroups.

## Issues continued

- There are no truly quantifiable measurement techniques.
*Sochaniwskj 82*
- There exists a general pessimism about pharmacological management.
*Arnold and Gross 77,Brody 77, Guerin 79, Bailey and Wadsworth 85, Crysdale 89*
- Many logistic and ethical issues are involved in the study of children with disabilities.
- There are many issues regarding long term utility and effects on overall health.
- We need clear definition of our outcome measures.
- Issues surrounding polypharmacy

## Long-standing anecdotal knowledge 	use of anticholinergics in pediatric populations

- Infants and young children are especially susceptible to toxic effects.
- There is a need for close supervision of infants and children with CP and other forms of brain damage when given these medications.
- Increased response to anticholinergics has been consistently reported in children with disabilities and dosage adjustments are required.

## ASSESSMENTAnterior Drooling represents only one element in the continuum of oral performance impairment

- Sialorrhea
- Speech problems
- Feeding and swallowing difficulties
- Structural and motor problems
- Upper respiratory congestion
- Aspiration

## Factors that need to be assessed to determine etiology

- Degree of global functional impairment in the child’s life secondary to drooling
- Amount of health care maintenance problems caused be drooling
- Integrity of the oral structure
- Oropharyngeal motor function
- Orofacial sensory perception and feedback
- * Rate of saliva secretion*
- Cognitive appreciation of salivary spill
*Blasco 1992*

## Therapies     Hierarchical, least invasive first

- Behavior Modification
- Biofeedback
- Oral Motor Therapy
- Speech Therapy
- Medication Therapy
- Orofacial Regulation Therapy
- Surgery
*Crysdale 1992, Nunn 2000*

## What does this population actually look like?

**Cerebral Palsy**   **0.2 to 0.5%**   *Lipkin 91*
**10% to 37%** have drooling problems significant enough to interfere with daily global function
*Ekedahl et.al. 74, Sochaniwskj 82, Blasco 92, Nunn 2000*
**Severe/Profound Mental Retardation**   **0.2% to 0.7%**
- An **unknown percentage** of these children are further handicapped by drooling
*Harris and Purdy 87, Crysdale and White 89, Limbrock et al 90*

## The gap between incidence and 	prevalence of DD/MR is closing	This translates into increasing

- Numbers of children
- Complexity
- Lifespans
- Integration into our communities with increasing expectations

## Increasing ComplexityMost of the children we see that need these agents have

- CNS developmental problems or damage that translates into a developmental disability or mental retardation.  *In addition they have a combination of*
- other chronic CNS illnesses such as Epilepsy or Movement Disorders
- multiple chronic general medical illnesses
- sensory or communication challenges
- co-morbid mental illness
- and severe behavior problems

## These kids haveFRAGILE BRAINS

## The average child referred to us 

- Is on 6 to 8 medications which have central nervous system activity - **POLYPHARMACY**
- 2 to 4 of these medications have significant **additive** anticholinergic activity
- 70% have 2 or more medical problems that contribute to their behavior presentation
- 1.5% to 5% are on drooling medications
*Stiefel et al (variation due to subgroups)*

## General medical issues related to the use of antimuscarinics

**Dental** - increased caries
**Gastrointestional** - constipation and worsening of gastroesophageal reflux
**Pulmonary** - increased problems with secretion clearing and pulmonary function
**CNS **- Irritability, agitation, sedation, hyperexcitability, confusion, decreased attention and concentration, decreased memory
**Cardiac **- increased heart rate
**Impaired temperature regulation** - decreased sweating
**Genitourinary **- retention
**Sleep** - impaired regulation and architecture
**Psychiatric** - the full spectrum of symptoms
*References available at sstiefel@hsc.utah.edu*

## How can adverse events be assessed in this population?

- Adverse events often manifest as behavior changes or problems.
- Assessment must first provide understanding of the child’s learning strategies or degree of cognitive disability.
- We must first establish a relationship and shared communication strategy  with the child. -*Fension 93*
- We must objectively be able to assess pain and discomfort
*Giusiano et al. 95, Collignon et al. 95, McGrath 96*
- Studies must be of sufficient length to evaluate long term outcomes and adverse events - **disease cycles**

## BEHAVIOR 	how do you quantitatively assess?			Behavior Equivalents

- Symptom of pain or discomfort
- Symptom of general medical condition
- Symptom of mental illness
- Symptom of side effect (iatrogenic)

## Behavior Assessment and Rating Scales	All children in studies must have a 

- Multidisciplinary evaluation that includes a
- Medical evaluation
- Developmental analysis
- Functional analysis of behavior
- Use of rating scales to provide data and evidence of change
*ABC, Reiss, DBC, Auchenbach, Connors, etc.*

## Do not just study children with Cerebral Palsy without cognitive disability or language problems

## Safe and ethical conduct of studies

- This is a vulnerable population, it is our responsibility to protect - part of this responsibility is in demanding meaningful studies.
- Need for multidisciplinary team assessment throughout the process. - *Crysdale and White 89*
- Need for agreement of description of etiology, pathology and subgroups - this forms the database of a consortium. -*Blasco and Allaire 92*
- Including subgroup response patterns
- Must study population across the spectrum of etiologies and complexity

## Safe and ethical conduct continued

- Increased length of time of the study to address
- use of outcome based research tools
- general medical adverse effects take time to develop
- long term follow-up
- tolerance
- Establishment and support for/of research and consortiums.
- Consent and study subject selection issues.

## Safe and ethical conduct continued

- IRB’s should include individuals with expertise in disabilities and children
- Ethicists
- State/Local disability Human Services rights oversight
- Clinicians and multidisciplinary teams that are aware of the issues in this population and have the expertise to monitor for adverse events
- It is critical to use independent assessors, not just caregivers
_**Always **_**include the child, adolescent or young adult in the process**

## Other recommendations for studies

- Need for consensus definition and assessment of significant impairment and etiology
-  Quantification of volumes
*Chin Dry System *and the consortium, weighing bibs, etc.
- Rating tools and inter-rater reliability
*Sochaniwskj 82, Blasco 92, Teacher’s Drooling Scale, etc.*
- Consensus of other necessary measures and degree of impairment caused by drooling
- Determination of subgroups with high likelihood of response

## Other recommendations continued

- Identify medications with good efficacy and good side effect/benefit ratios
- Identify and support need for NIH,NIMH, etc. studies regarding therapy choice, drug choice in medications of the same class, and polypharmacy

## Pediatric Formulations

**Delivery **
- oral forms, many of these children have swallowing difficulties
- transdermal - risk of chewing, rashes
- many safety issues
**Pharmacokinetics**
- absorption - quaternary amine 10 to 25%
- metabolism and clearance is different in children
- tolerance

## Pediatric Formulations Continued

**Blood-Brain Barrier**
- many of these children have ongoing insults - the blood brain barrier is variably intact ( E.g.. Hydrocephalus, Epilepsy, Immune Disorders, Self Injurious Behavior, Traumatic Brain Injury, etc.)
**Need for broad titration and dosage latitude**
- usually addressed retrospectively
**These medications should not be extemporaneously formulated**
**Issues of polypharmacy**

## Guidance for dosing and management on product labelsDiscussion of

- Adverse events
- Discussion that behavior changes may herald adverse effects
- Subgroups are the most likely to respond
- Additive polypharmacy
- Chronic general medical and psychiatric problems
- Possible tolerance cycle
*Camp-Bruno 89, Reddihough et al. 90*
- A conservative titration schedule

## Discussion continued

- Other therapies (a hierarchical approach)
- Dental recommendations for surveillance and intervention - Arnup and Crossner 90, Hallet et al. 95
- Interface with electronic management software - is there an opportunity?

## Thank you for your kind attention and consideration of these recommendations