A Guide for Detecting Psychoactive Medication
Side Effects in Patients with ID (Intellectual
Disabilities) and ASD (Autism Spectrum
Disorders)
The case of antipsychotic drugs
Professor Angela Hassiotis
Division of Psychiatry
UK
NADD 31st San Antonio-Precon with L Charlot and S Ruedrich
Disclosures
• Member of NICE guideline development group on
challenging behaviour and ID
• Member of NICE guideline development group on
mental disorders and ID
• Funded by NIHR (RfPB and HTA programmes)UK
• Honoraria from academic institutions and Novartis
Glossary
• ID: Intellectual Disability
• ASD: Autism Spectrum Disorders
• CB: Challenging Behaviour (also, behaviour that
challenges)
• AP: Antipsychotics
• CYP: Child and Young Person
• DA: dopamine
Will cover
• Use of antipsychotic (AP) medication
• Side effects of AP
• Presentation of side effects of AP in persons with
communication challenges
• Aspects of good clinical practice
Use of antipsychotic medication-what for?
• To treat mental illness (psychosis, BAD, severe
depression) (diagnosis based)
• To treat agitation and aggression (symptom
based)
Dementia
People with ID
People with ASD
• Other (e.g. anti-emetic)
Types of antipsychotics
• Typical (1st generation, e.g. chlorpromazine,
haloperidol)
• Atypical (2nd generation, e.g. risperidone,
olanzapine)
• New drugs, e.g. aripiprazole
Mode of action
• Blockade of D2
receptors (typical)
• Blockade of D2 and
5HT2A &2C receptors
(atypical)
Slides in this and next page are drawn from
http://www.brain-health.co/images/Atyp-Recep-MOA-CMEMarch-2012.pdf
file://ad.ucl.ac.uk/slms/home3/rejuaha/Downloads/Santosh-Medication-in-ASD-whatworks-and-what-doesnt%20(2).pdf
Trends in dementia for agitation and
aggression
• Only risperidone is licensed in Europe and none in
the USA
• Decrease in prescriptions of antipsychotics over
time (up to 50% in UK-wide audit)
• Prescriptions may exceed the 6 week threshold or
the 12 week good practice guidance
• Off-license use
• 62% of those on antipsychotics >6 months
Trends in people with ID and behaviour that
challenges
• Challenging behaviour has no specific diagnostic
status
• Episodic aggression, tantrums, agitation
• Currently 50% of adults with ID are estimated to
receive psychotropic medications, 23% of whom
are on antipsychotics (Cooper et al 2007)
Findings from a national audit of medication prescribing
(POMH-UK; Paton et al, 2011)
Trends in ASD with ID and aggression
• Medication is used for associated symptoms of
agitation and aggression, hyperactivity, rituals and
repetitive behaviours
• NICE recommends no more than 4 weeks of
antipsychotics if high risk of injury to self/others
• 10-year increase in prescriptions for psychotropic
drugs (30% to 45%)
• Increasing prescriptions with increasing age, e.g.
56% in 6-11 year olds to 73% in 18-21 year olds
Trends in ASD with ID and aggression
• Once started, there is 11-fold risk of remaining on
medication
• Correlation with polypharmacy
• In the UK primary care, 29% of the prescriptions in
ASD CYP were for psychotropic medication
• 7.3% of those were for antipsychotics
• Polypharmacy was seen in 34% of those receiving
psychotropic medication
What is the evidence?
• Not good enough for adults-possibly minimal
impact on aggression
• NACHBID trial suggests no benefit at all (Tyrer et
al 2008)
• In children, the RUPPAN study shows
improvements in 75% of treated children vs 11%
in the control group
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536539/)
Comments on clinical significance in recent studies
in children with ASD and challenging behaviour
Discontinuation
• Discontinuation of antipsychotic medication was
associated with re-emerging of CB in CYP (Findling
et al, 2014; RUPPAN, 2005)
• Discontinuation appears to improve behavioual
outcomes in adults with ID and CB
(http://onlinelibrary.wiley.com/doi/10.1111/j.13652788.2012.01631.x/pdf)
• Antipsychotics can be withdrawn within 14 weeks
Why do we have side-effects?
Clinical impact of adverse effects.
Hamer S , and Haddad P M BJP 2007;191:s64-s70
©2007 by The Royal College of Psychiatrists
Side effects
• Somnolence
• extrapyramidal
symptoms
• increased prolactin
concentrations*
• significant weight gain
• cardiovascular
dysfunction
*: hyperprolactinemia is
associated with amenorrhea,
erectile dysfunction and
osteoporosis
Metabolic syndrome
• no clinical or statistically
significant differences in
• Obesity
metabolic indices between
people with ID treated with
• insulin resistance,
anti-psychotics and those who
• impaired glucose
were anti-psychotic naïve,
tolerance,
although there was a trend
towards increased rates of
• dyslipidaemia
type 2 diabetes in the treated
group (Frighi et al. 2011)
(Newcomer 2007; Ruedrich, 2008)
EPSE
• UK
Lack of documentation of
EPSEs in 6/10 patients in
national audit (Paton et al,
2011)
• Tardive Dyskinesia
(TD) is common long
term side effect of AP
drugs
• Consists of repetitive,
purposeless
movements which can
involve the face, trunk,
and limbs
Neuroleptic Malignant Syndrome (NMS)
•
•
•
•
Extremely severe reaction to AP but rare (0.2-3%)
Can be life threatening
First described by French specialists in 1956
Symptoms: muscle rigidity, fever, autonomic
instability (unstable BP), cognitive changes, e.g.
delirium
• Lab findings: elevated plasma creatinine
phosphokinase.
• Can be mistaken as symptoms of mental illness
• Stop medication
Risk factors of NMS
• Rapid reduction in DA
High doses
• Sympathodrenal hyperactivity and autonomic
dysfunction (defect of calcium regulating proteins
in the sympathetic neurons)
• Long acting forms, i.e. depot
• Concurrent use of AP
• Young males
• Patients with Lewy Body Dementia
Challenges in monitoring side effects in
people with ID and ASD
• Informant awareness
• Service restrictions
(medication an option if
lack of supervision)
• Benefit vs harm
Person
• Communication
limitations
• Lack of concentration
• Mannerisms and
stereorypies relating to
ID/ASD
• Neurological problems
Side effects: avoid or detect?
Side-effect
Scale(s)
Reference
Abnormal Involuntary
Movements Scale
(AIMS)
Guy (
EPS
Tardive
dyskinesia
1976
Akathisia
Barnes Akathisia Scale Barnes (
Parkinsonism
Simpson-Angus Scale
(SAS)
Extrapyramidal
Symptom Rating Scale
(ESRS)
Arizona Sexual
Experiences scale
(ASEX)
Massachusetts General
Hospital Sexual
Functioning
Questionnaire
Non-syndromespecific scale
Sexual dysfunction
)
1989
)
Simpson & Angus (
Chouinard et al (
McGahuey et al (
1970
1980
2000
Labbate & Lare (
)
)
)
2001
)
2005
Global side-effects
Modified Rush Sexual Rao et al ( )
Inventory
1987
UKU Side Effect Rating Lingjaerde et al ( )
Scale
Collegium Internationale
AMDP-5
1986
Psychiatriae Scalarum (
Day et al (
Liverpool University
Neuroleptic Side-Effect
Rating Scale (LUNSERS)
1995
Table 1
Examples of ratings scales used to
assess side-effects of antipsychotics
•EPS, extrapyramidal side-effects;
AMDP-5
)
)
BJP August 1, 2007 vol. 191 no.
50 s64-s70
ID specific
• Matson Evaluation of Drug Side Effects (MEDS)
• 90 item informant based questionnaire
• (1) cardiovascular and hematological (e.g., persistent high blood
pressure), (2) gastrointestinal (e.g., irregular stools, change in
appetite), (3) endocrine/genitourinary (e.g., urinary hesitancy or
retention, enuresis), (4) eye/ear/nose/throat (e.g., excessive salivation,
sinus congestion, visual sensitivity to light), (5)
skin/allergies/temperature (e.g., dry skin, fever), (6) central nervous
system (CNS)-general (e.g., changes in sleep patterns,
learning/memory impairments, depressed affect), (7) CNS-dystonia
(e.g., eyes locked upward), (8) CNS-parkinsonism/dyskinesia (e.g.,
disturbed gait, abnormal tongue/oral movements, facial grimacing),
and (9) CNS-behavioral/akathisia (e.g., motor restlessness or
agitation, self-injury)
Aspects of good practice
•
•
•
•
•
•
•
•
Use of clinically effective dose
Avoid polypharmacy
Assess behaviour
Assess impact of medication
Consider other treatments-psychosocial
Enhance communication ability
Follow guidelines for monitoring AP side effects
Stop increasing dose/change medication if side
effects severe
What to do to help manage side effects
•
•
•
•
•
Discuss AP side effects at consultations
Use easy read and other materials
Ensure regular health checks
Provide advise on eating and exercise
Formulate discontinuation plan early on
All antipsychotic drugs are not the same
http://bjp.rcpsych.org/content/199/4/269.full.pdf
• High potency
more EPSE
less sedation
• Atypicals most expensive
• All APs are D2 receptor blockers but variation in 5-HT2
blockade
• Weight gain++ with olanzapine and clozapine
• Atypicals have better ERSE profile but not risperidone++
• Typicals more sedating
• Atypicals increase prolactin less than typicals
…as there are many real differences among drugs,
that the physician should adapt the treatment
accordingly to the individual patient through a shared
decision-making process.
Patients have different preferences and at the end it
is they who must take the medication. Some patients
want to avoid weight gain or EPS or sexual sideeffects, and others want to receive the most
efficacious compound. The best antipsychotic drug
will not work if the patient does not take it, so there is
a role for depot formulations. We feel it is important to
empower the patient to make informed decisions
about which drug and dose to take as well as the
route of delivery, which may lead to better feedback
and adherence….
An example of a CYP service
Next steps
•
•
•
•
•
Need for independent trials of APs
Audits of practice
Continuous education of clinicians and carers
Review of medication is everybody’s responsibility
Work with the patient and his/her network
Thank you
a.hassiotis@ucl.ac.uk
http://www.ucl.ac.uk/slms/people/show.php?UPI
=AHASS94