Download Irritability (Cont`d)

Practical Psychotropic Drug
Management in Developmental
Disabilities
Craig A. Erickson, M.D.
Director, Developmental Disability Research and Treatment in
Psychiatry
Director, Fragile X Research & Treatment Center
Medical Director, P3 Southwest Neurodevelopmental Disorders
Inpatient Unit
Director of Research, The Kelly O’Leary Center for Autism Spectrum
Disorders
Associate Professor of Psychiatry
Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine- Affiliated
Conflicts of Interest
Source
Consultant
(past* or
present^)
Stock or
Equity
Interest
Bristol-Myers Squibb
Speakers
Bureau
Research Support
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present^)
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Roche/Genentech
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Seaside Therapeutics
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Novartis
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Pharmaceuticals
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US Dept of Defense
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AACAP
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FRAXA Research
Foundation
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Alcobra
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Neuren
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Simons Research
Foundation
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Autism Speaks
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Cincinnati Children’s
Hospital Research
Foundation
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John Merck Fund
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National Fragile X
Foundation
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Honorarium/
Support for this
Talk
Roadmap
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Target symptom approach to treatment
PRN medications
Polypharmacy
Medication Discontinuation
Vignette Examples
Target Symptoms for
Medication
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Motor hyperactivity and inattention
Interfering ritualistic behavior
Aggression, self-injury, property
destruction
Target Symptoms Continued:
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Mood disturbances: depression, bipolar
Anxiety: panic attacks, agoraphobia,
general anxiety, phobia, PTSD
Others: sleep disturbances, pica,
inappropriate sexual behavior
Motor Hyperactivity and
Inattention
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Psychostimulants: methylphenidate,
dextroamphetamine, mixed amphetamine
salts
Alpha-2 agonists: guanfacine, clonidine
Non-stimulants: atomoxetine, bupropion,
tricyclic antidepressants
Psychostimulants
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Work quickly
Side effects: reduced appetite, insomnia,
tics, increased pulse/blood pressure
May cause behavioral worsening
May need to be given multiple times per
day
Need new prescription each month
Alpha-2 Agonists
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Need to monitor blood pressure and heart
rate
Can be sedating
Generally don’t make symptoms worse
Need to be given 2-3 times per day
Non-Stimulants
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Atomoxetine: effective in ADHD;
preliminary studies in developmental
disabilities.
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May take longer to work than stimulants.
Generally won’t make tics worse.
May help with comorbid mood and/or
anxiety.
Non-Stimulants (Cont’d)
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Bupropion: has been shown to be
effective for ADHD.
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Not well-studied in developmental disabilities.
Can lower the seizure threshold and should
NOT be given to a patient with a history of
seizures or active seizure disorder.
Can make tics worse.
Non-Stimulants (Cont’d)
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Tricyclic antidepressants: not well-studied
in developmental disabilities.
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Associated with side effects including: dry
mouth, blurry vision, constipation.
Can lower the seizure threshold.
Can affect cardiac rhythm.
Ritualistic Behavior
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Selective Serotonin Reuptake Inhibitors
(SSRIs)
 Fluoxetine
 Fluvoxamine
 Sertraline
 Paroxetine
 Citalopram
 Escitalopram
SSRIs
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Data indicate SSRIs may be more effective
in post-pubertal vs. pre-pubertal
individuals with developmental disabilities
Side effects: insomnia, sedation, stomach
upset, sexual dysfunction, weight gain
Can generally be given once a day
Concern about increasing suicidal
thinking/behavior
Irritability: Aggression, SelfInjury, Severe Tantrums
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Typical antipsychotics
Atypical antipsychotics
Mood stabilizers
Alpha-2 agonists
Naltrexone
Irritability (Cont’d)
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Typical Antipsychotics
 Haloperidol
 Thioridazine (rare use, sudden death)
 Chlorpromazine
 Trifluoperazine
 Fluphenazine
Irritability (Cont’d)
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Typical Antipsychotics
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Side-Effects
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acute extrapyramidal symptoms (EPS), tardive
dyskinesia (TD), sedation, weight gain, drooling
Irritability (Cont’d)
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Atypical Antipsychotics
 Clozapine
 Risperidone
 Olanzapine
 Quetiapine
 Ziprasidone
 Aripiprazole
 Paliperidone
Clozapine
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Common side effects include weight gain,
sedation, drooling
Can lower the seizure threshold
Agranulocytosis and need for careful blood
monitoring
Risperidone
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Well-studied in autism (FDA approval) and
mental retardation associated with
behavioral dyscontrol
Common side effects: weight gain,
sedation (transient), drooling, elevated
prolactin
Olanzapine
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Only small controlled studies in
developmental disabilities
Common side effects: weight gain (at
times significant), has been associated
with glucose and lipid dysregulation,
sedation
Quetiapine
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No controlled studies in developmental
disabilities
Common side effects: weight gain (may
be less prominent than with clozapine and
olanzapine), sedation, orthostatic
hypotension if dose increased too quickly
Ziprasidone
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No controlled studies in developmental
disabilities
Common side effects: sedation
(transient), occasional insomnia or
behavioral activation. Not associated with
significant weight gain
Should not be given to patients with
cardiac problems
Aripiprazole
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Positive controlled study in youth with
autism spectrum disorders
Common side effects: EPS and
nausea/vomiting if given at too high a
starting dose. Akathisia. Occasionally
transient sedation or activation. Not
associated with significant weight gain or
prolactin elevation
Paliperidone
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Major active metabolite of risperidone
Potentially fewer drug-drug interactions
Once daily dosing
Potentially less weight gain and prolactin
elevation
Irritability (Cont’d)
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Mood Stabilizers
 Valproic acid
 Lithium
 Carbamazepine
 Gabapentin
 Topiramate
 Oxcarbazapine
Valproic Acid
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The only controlled study in autism found
no drug vs. placebo difference
Common side effects: sedation, weight
gain
Need to monitor blood level for
therapeutic range and to follow liver
function tests
May be useful in patients with seizures
and aggression
Lithium
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No controlled studies in developmental
disabilities
Common side effects: tremor, polydipsia,
polyuria, weight gain
Need to monitor blood for therapeutic
range and to follow kidney and thyroid
function
Carbamazepine
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No controlled studies in developmental
disabilities
Common side effects: dizziness
Need to monitor blood level for
therapeutic range and to follow blood
count and sodium level
Oxcarbazepine
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Not well studied in developmental
disabilities
Negative study in adolescent bipolar
disorder
Need to monitor serum sodium
Gabapentin
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No controlled studies in developmental
disabilities
Common side effects: some sedation,
some weight gain
No need to monitor blood levels
Not particularly effective on a clinical basis
Topiramate
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No controlled studies in developmental
disabilities
Common side effects: sedation, cognitive
dulling. Not associated with weight gain
No need to monitor blood levels
Irritability (Cont’d)
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Alpha-2 Agonists
 Guanfacine: not particularly effective for
aggression
 Clonidine: can be effective for
aggression. Need to balance sedation
vs. clinical benefit
Need to monitor blood pressure and heart
rate
Irritability (Cont’d)
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Naltrexone
Not effective on a clinical basis
No significant side effects, except:
Need to monitor liver function
Irritability: Conclusion
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Best evidence based treatments in
persons with developmental disabilities:
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Risperidone
Aripiprazole
Mood - Depression
SSRIs: fluoxetine, paroxetine,
citalopram, escitalopram, fluvoxamine
etc.
 Bupropion
 SNRIS: Venlafaxine (elevated blood
pressure), duloxetine
 Mirtazapine (weight gain, sedation)
 Tricyclic antidepressants
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Mood – Bipolar Disorder
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Valproic acid
Lithium
Carbamazepine
Gabapentin
Topiramate
Lamotrigine (Steven’s Johnson Syndrome)
Anxiety
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SSRIs/SNRIs generally most effective
Cautious use/avoid benzodiazepines
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Lorazepam, alprazolam, clonazepam,
diazepam etc.
Anxiety
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Buspirone: few side-effects combined with
limited benefit
Consider mirtazapine (dosed at bedtime)
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Commonly associated with sedation and
increased appetite
Sleep Disturbance Insomnia
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Diphenhydramine (paradoxical rxt’n)
Clonidine
Trazodone (priapism)
Chloral hydrate
Benzodiazepines (paradoxical rxt’n)
Melatonin
Mirtazapine
Pica
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SSRIs
Antipsychotics
Behavioral strategies
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All strategies may hinge on framing what
drives pica: anxiety/impulsivity/something
else/unknown
Inappropriate Sexual
Behavior
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SSRIs
Hormonal strategies
Behavioral strategies
PRN Medications
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“As needed” drugs
“Chemical restraints”
Common in mental health outside of MR/DD
world
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Beta blockers for social anxiety
Benzodiazepines and hydroxyzine for anxiety/panic
Antipsychotics for agitation associated with psychotic
and bipolar illness
PRN Medications
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Acute Inpatient Psychiatry Units
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About 50% of all inpatients receive at least
one PRN medication during course of hospital
stay
Most frequently antipsychotics and/or
benzodiazepines
 Classic PRN combo for agitation: 5mg haloperidol
+ 2mg lorazepam IM
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Usher K, Luck L. Psychotropic PRN: a model for best practice management of acute psychotic behavioural disturbance in
inpatient psychiatric settings. J Ment Health Nurs. 2004 Mar;13(1):18-21
PRN Medications
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Long-term state psychiatric facilities
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In one study, 23% of residents received at
least one PRN medication in last month
Craig TJ, Bracken J. An epidemiologic study of prn/stat medication use in a state psychiatric
hospital. Ann Clin Psychiatry 1995 Jun;7(2):57-64
PRN Medications
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Nursing homes
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35% of all psychotropic drugs prescribed for
PRN use
Stokes J.A.; Purdie D.M.; Roberts M.S. Factors influencing PRN medication use in nursing homes. Pharmacy World and
Science, Volume 26, Number 3, June 2004 , pp. 148-154(7)
PRN Medications
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Supervised living environments
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No systematic studies look at % of patients
with PRN orders?
Clinically we see minority of patients with
behavioral PRNs
PRN Medications
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Issues:
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Chronic, frequent use: If you need it all the
time is it really a PRN?
Who makes the call: Who/Whom are the
appropriate personnel to decide if PRN
needed?
PRN Medications
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Issues Continued:
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Aren’t you just sedating someone?
Risk of falls/hypotension/dystonic
reaction/disinhibition: ie side effects.
PRN Medications
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Maybe best if narrowly defined
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PRN use prior to long trips or going to the
doctor’s office/other appointments
PRN for sleep if patient still awake after X
number of hours/at a certain time
PRN Medications
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Frequency of administration is key
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If not needing it for months and months,
consider getting rid of it
If need it every other day, look at adjusting
scheduled meds/behavioral intervention
changes to try and limit need for PRN
Polypharmacy
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A chronic problem in our patient
population
“Layers of drugs”
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A drug gets added with no plans to remove a
preexisting agent
Polypharmacy
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Can end up on drugs with opposite effects
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Stimulants and benzodiazepines: “Uppers and
downers”
Polypharmacy
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In our clinic most commonly seen with
borderline personality disorder
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May be do to fluctuating moods, severity of
agitation, anxiety, psychotic-like phenomena
Can almost read a med list and predict the
diagnosis
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Antipsychotics, plus antidepressants, plus
benzodiazepines, plus maybe a stimulant
Polypharmacy
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How To Avoid
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Target Symptom Approach
Be sure each drug has defined target symptom(s)
 If a drug does not adequately treat a target
symptom, discontinue it
 If adding a drug, always consider what the new
drug could replace
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Polypharmacy
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Cross-titration
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Slowly increasing a new drug while slowly
decreasing the drug it replaces
May takes weeks to a few months, but can in
some cases be much faster
 Goal is to not exacerbate behavior/symptoms in
the process
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Medication Discontinuation
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Goal is least number of drugs at lowest
doses
Medication Discontinuation
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Need behavioral/symptom stability before
slowly removing effective agents
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Like to see at least 6-12 months of good
symptom control before removing slowly a
effective drug
Medication Discontinuation
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Good plan to at least try slow med
reduction, especially if significant sideeffects are at risk/developing
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Worst case is behavior worsens and dose
need be restored
Do run risk that behavioral control will not be
duplicated when dose restored
Vignettes
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13 year old male with autistic disorder, IQ=50
Reported failures/lack of significant response
of/from aripiprazole, risperidone, quetiapine,
guanfacine, Adderall
BMI at >99% for age and gender
Gained weight on all antipsychotics
Also on Concerta 54mg, trazodone 50mg for
sleep and quetiapine 200mg TID which is
viewed as partially effective
Admitted with increased physical aggressiongrabs, hits, spits
Vignettes
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4 year old with autism, non verbal, intense
hyperactivity, aggression and tantrums in
developmental preschool
BMI at 50% for age
No major medical problems, no previous
medications
Vignettes
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14 year old with ASD, IQ 80, intensely fears
fire drills, has outbursts going to school,
attacks parents on school days, emesis in the
morning at school, no medical problems
Recently started aripiprazole 5mg daily, 50%
reduction in agitation, but still missing 2 days
of school per week
Vignettes
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7 year with ASD, intermittent agitation
controlled on risperidone, admitted due to
running away from school in the street,
hyperkinetic, cannot sit still, unable to stay in
seat at school
Current medication: risperidone .5mg BID,
clonidine .2mg HS for sleep, melatonin 3mg
QHS for sleep
Previous medication trials: daytime clonidine
too sedating, guanfacine non helpful
Unable to swallow pills
Vignettes
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Age 12, ASD, explosive aggression, history of
abnormal EEG, never treated for frank epilepsy
No other medical problems, BMI 50% for age.
Current meds: naltrexone, lithium, risperidone,
clonidine .1mg TID and .2mg HS
Past med failures: quetiapine, aripiprazole,
guanfacine, olanzapine, haloperidol, fluoxetine,
clonazepam
Vignettes
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Age 16, ASD, severe self-injury, history of
retinal detachments, seizure disorder- last
seizure 18 months ago, stable on valproic acid
Current meds: haloperidol 10mg TID,
trazodone 150mg HS for sleep, Depakote ER
1000mg BID, guanfacine 1mg TID
BMI 50%, no other medical issues other than
epilepsy
Previous medication failures: aripiprazole,
risperidone, quetiapine, olanzapine,
chlorpromazine; was on aripiprazole and
Vignettes
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17 year old developmental disability, no ASD,
FAS, history of physical and sexual abuse
Intermittent about 3 times per week major
aggression, mainly towards mother
Admitted 4 times in last 12 months
Failed aripiprazole, risperidone, olanzapine,
ziprasidone, guanfacine
Current meds: Quetiapine 300mg BID,
minimally effective; clondine .2mg HS for
sleep, fluoxetine 20mg daily for history of
anxiety
Vignettes
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17 year old developmental disability, no ASD,
FAS, history of physical and sexual abuse
Intermittent about 3 times per week major
aggression, mainly towards mother
Admitted 4 times in last 12 months
Failed aripiprazole, risperidone, olanzapine,
ziprasidone, guanfacine
Current meds: Quetiapine 300mg BID,
minimally effective; clondine .2mg HS for
sleep, fluoxetine 20mg daily for history of
anxiety
Vignettes
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15 year old with ASD, IQ 125, admitted with
self-inflicted chest inflicted chest laceration
from knife, bullied at school, suicidal ideation
for six months, insomnia, has lost 15 pounds in
six months
No medication now or in the past
QUESTIONS?
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