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

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 (1 st generation, e.g. chlorpromazine, haloperidol) Atypical (2 nd generation, e.g. risperidone, olanzapine) New drugs, e.g. aripiprazole

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

file://ad.ucl.ac.uk/slms/home3/rejuaha/Downloads/Santosh-Medication-in-ASD-what- works-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/ ) 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.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

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 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)

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-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

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 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 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.

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 everybodys responsibility Work with the patient and his/her network

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

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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