A Guide for Detecting Psychoactive Medication Side Effects in Patients with ID (Intellectual...
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A Guide for Detecting Psychoactive Medication Side Effects in Patients with ID (Intellectual Disabilities) and ASD (Autism Spectrum Disorders) The case
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
Slide 2
Slide 3
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
Slide 4
Glossary ID: Intellectual Disability ASD: Autism Spectrum
Disorders CB: Challenging Behaviour (also, behaviour that
challenges) AP: Antipsychotics CYP: Child and Young Person DA:
dopamine
Slide 5
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
Slide 6
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)
Slide 7
Types of antipsychotics Typical (1 st generation, e.g.
chlorpromazine, haloperidol) Atypical (2 nd generation, e.g.
risperidone, olanzapine) New drugs, e.g. aripiprazole
Slide 8
Mode of action Blockade of D2 receptors (typical) Blockade of
D2 and 5HT 2A &2C receptors (atypical) Slides in this and next
page are drawn from
http://www.brain-health.co/images/Atyp-Recep-MOA-CME-
March-2012.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
Slide 11
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)
Slide 12
Findings from a national audit of medication prescribing
(POMH-UK; Paton et al, 2011)
Slide 13
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
Slide 14
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
Slide 15
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/ )
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536539/
Slide 16
Comments on clinical significance in recent studies in children
with ASD and challenging behaviour
Slide 17
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.1365-
2788.2012.01631.x/pdf )
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-
2788.2012.01631.x/pdf Antipsychotics can be withdrawn within 14
weeks
Slide 18
Why do we have side-effects?
Slide 19
Clinical impact of adverse effects. Hamer S, and Haddad P M BJP
2007;191:s64-s70 2007 by The Royal College of Psychiatrists
Slide 20
Side effects Somnolence extrapyramidal symptoms increased
prolactin concentrations* significant weight gain cardiovascular
dysfunction *: hyperprolactinemia is associated with amenorrhea,
erectile dysfunction and osteoporosis
Slide 21
Metabolic syndrome Obesity insulin resistance, impaired glucose
tolerance, dyslipidaemia (Newcomer 2007; Ruedrich, 2008) no
clinical or statistically significant differences in metabolic
indices between people with ID treated with anti-psychotics and
those who were anti-psychotic nave, although there was a trend
towards increased rates of type 2 diabetes in the treated group
(Frighi et al. 2011)
Slide 22
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
Slide 23
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
Slide 24
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
Slide 25
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
Slide 26
Side effects: avoid or detect?
Slide 27
Side-effectScale(s)Reference EPS Tardive dyskinesia Abnormal
Involuntary Movements Scale (AIMS) Guy ( 1976 ) AkathisiaBarnes
Akathisia Scale Barnes ( 1989 ) ParkinsonismSimpson-Angus Scale
(SAS) Simpson & Angus ( 1970 ) Non-syndrome- specific scale
Extrapyramidal Symptom Rating Scale (ESRS) Chouinard et al ( 1980 )
Sexual dysfunctionArizona Sexual Experiences scale (ASEX) McGahuey
et al ( 2000 ) Massachusetts General Hospital Sexual Functioning
Questionnaire Labbate & Lare ( 2001 ) Modified Rush Sexual
Inventory Rao et al ( 2005 ) Global side-effectsUKU Side Effect
Rating Scale Lingjaerde et al ( 1987 ) AMDP-5 Collegium
Internationale Psychiatriae Scalarum ( 1986 ) Liverpool University
Neuroleptic Side-Effect Rating Scale (LUNSERS) Day et al ( 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
Slide 28
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)
Slide 29
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
Slide 30
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
Slide 31
All antipsychotic drugs are not the same
http://bjp.rcpsych.org/content/199/4/269.full.pdf
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
Slide 32
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 side- effects, 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.
Slide 33
An example of a CYP service
Slide 34
Next steps Need for independent trials of APs Audits of
practice Continuous education of clinicians and carers Review of
medication is everybodys responsibility Work with the patient and
his/her network
Slide 35
Thank you Thank you [email protected]
http://www.ucl.ac.uk/slms/people/show.php?UPI =AHASS94
[email protected] http://www.ucl.ac.uk/slms/people/show.php?UPI
=AHASS94