Pharmacological Treatments for Psychiatric Disorders & Challenging Behaviours Jeremy Turk Institute of Psychiatry, King’s College, University of London Child & Adolescent Mental Health Neurodevelopmental Services, South London & Maudsley Mental Health Foundation NHS Trust Great Ormond Street Children’s Hospitals NHS Foundation Trust

Pharmacological Therapies: Symptomatic Psychiatric Aetiology

Disorder Specific

Specific

Medication may be useful for: Hyperactivity

& attention deficit disorders Aggression & violence Anxiety Self-injurious behaviour Epilepsy & associated behavioural problems Sleep disturbance Mood disorder: unipolar, bipolar, cyclical Obsessive-compulsive disorder Social aloofness Eating disorder Early onset psychosis

Medication should never be the initial intervention. Consider psychological, educational, family and social approaches first.

Thorough multi-disciplinary assessment must be undertaken.

Other interventions should have been tried.

If problems still persist, consider medication in addition to other approaches as a means to an end - not an end in itself.

Beware of diagnostic complexities & atypical presentations

Treat symptoms (e.g. selfinjury, aggression, overactivity) not syndrome (e.g. fragile X syndrome).

Undertake a clinical trial of medication  Does

 Are

it work or not?

there side-effects?

Consider the cost-benefit ratio 

What is the likelihood of improvement?



How important is this?



What are the likelihoods of side-effects?



How serious might they be?

Beware of the increased risk of adverse effects in people with intellectual disability and other neurodevelopmental disabilities.

If medication does not work, stop it!

If medication does work:  give

it for the minimum time possible

 frequent

monitoring and reviews

regarding: continuing possible

need

adverse effects

Evidence-based pharmacological therapies  Psychostimulants,

tricyclics & clonidine for hyperactivity & attentional

deficits  “SSRI’s”

for depression, anxiety & obsessive-compulsive features

 Anticonvulsants

for cyclical (& not so cyclical) mood & behaviour

disorders (Turk 2012)  Melatonin

for sleep induction problems (Turk 2003, 2010)

 Clonidine

for sleep maintenance problems (Ingrassia & Turk 2005)

 Atypical

antipsychotics for early onset psychosis

Medication: ADHD Methylphenidate,

Dexamphetamine

 Rapid, slow & pulsatile release preparations Clonidine Tricyclics* SSRI’s* Folic

acid* Atomoxetine Atypical antipsychotics * Anticonvulsants* (* = unlicenced)

Hyperactivity & Attention Deficit Disorders First

line treatment = central nervous system stimulants

Methylphenidate, Modified

dexamphetamine, Adderal (in US)

release preparations:

 Ritalin SR  Concerta  Equasym XL  Medikinet XL  Elvance (lisdexamphetamine mesylate)

Stimulants: downsides Lack

of response (30%) Paradoxical excitation Overfocussing Insomnia Appetite, weight & growth suppression Headaches, tummy aches, dizziness ↑ pulse & blood pressure Tic disorders & nervous twitching Anxiety, mood lability, psychosis

Downsides for those with intellectual disability Difficulty

swallowing Or at least difficulty swallowing whole tablets without crunching them Raised rates of adverse effects Need for lower dosage Need for more careful, frequent and intensive monitoring Heightened individuality of clinical response “start low – go slow” Risk of commencing at too high a dosage

Other Options: α-2A

noradrenergic receptor agonists – Clonidine, Guanfacine – Lack appetite and sleep disturbance – Good for tic disorders – But sedation & ↓ blood pressure Tricyclic antidepressants – Imipramine, Amitriptyline – Good for anxiety, depression, enuresis, tics, insomnia – May need to do ECG ? Calming SSRIs – as above

Clonidine (Ingrassia & Turk, 2005) α2A

noradrenergic receptor agonist

Shown

efficacy for anxiety, overactivity, impulsiveness, inattentiveness

Mildly

sedating, mildly hypnotic

Good

for tics & Tourette’s

Good

for repeated night time waking

No

effect on appetite

Can

drop your blood pressure

25-300

μg daily in divided doses

Atomoxetine: Selective

norepinephrine reuptake inhibitor Evidence for benefits in children & young people of average intellignece Less evidence for benifits in those with intellectual disability and/or ASD Upset stomach, weight change, dizziness Dry mouth, difficulty urinating, nausea, vomiting Constipation, sexual problems, insomnia, fatigue  heart rate & blood pressure Hives, swelling Hepatotoxicity, suicidal ideation & behaviour

Myths about stimulant medication & intellectual disability 1.

2.

3.

4.

5.

Overactivity, inattentiveness & impulsiveness are to be expected in children with intellectual disability. ADHD can not be diagnosed in children with intellectual disability. Stimulants are contraindicated in children with intellectual disability and/or autistic disorders. There is no evidence base for the use of stimulants in children with intellectual disability. The risk of side effects is too great to justify their use.

Decision regarding which product to use should be based on: Presence

of co-occurring conditions e.g. tic disorders, Tourette’s, epilepsy, anxiety, insmonia Different adverse effects of the drugs Compliance issues e.g. midday treatment doses at school Tablet v capsule v liquid Drug diversion and/or misuse Individual preference Cost (if there is a choice)

Self-injurious behaviour #1: Self-injury

triggers release of endogenous opioids producing pleasurable sensations which are positively reinforcing.

→opioid

antagonist: naltrexone

→pleasurable

sensations extinguished →aversive consequence to self-injury →↓ frequency & intensity of behaviour

Self-injurious behaviour #2: Self-injury Prescribe

is a form of tic disorder medication for tics

– Butyrophenones – haloperidol – Dibutylphenylpiperidone – pimozide – Substituted benzamide – sulpiride – α-2A agonist – clonidine – Atypical antipsychotics: risperidone, aripiprazole

Self-injurious behaviour #3: Self-injury

is a form of obsessive-compulsive

disorder Prescribe

anti-obsessive agents

– clomipramine – fluoxetine – sertraline – paroxetine – citalopram

Melatonin (Turk, 2003) N-acetyl-5-methoxytryptamine Pineal

indole diurnal secretion variation widely available as food supplement in North America unlicensed in U.K. - only prescribable on named patient basis

Tryptophan Serotonin N-acetylserotonin Melatonin (N-acetyl-5-methoxytryptamine)

JAN ET AL 1994: 15 children, most with multiple neurological disabilities  improved sleep  “significant health, behavioural & social benefits” BUT  responses not always complete  responses varied considerably depending on type of sleep disturbance  not double-blind 

Melatonin is: Highly

beneficial, short-term, rapid-onset & safe treatment for intractable sleep disturbance Therapeutic dose not predicted by: – severity of sleep disturbance – severity of intellectual disability – presence/absence of autism Habituation common but not universal Modified-release version (Circadin) probably no better than immediate-release – but cheaper!

Acebutolol: selective

beta-1 adrenergic agonist De Leersnyder et al (2003) melatonin antagonist nine children with Smith-Magenis syndrome severe and intractable sleep difficulties successful suppression of inappropriately high morning melatonin levels improved behaviour and concentration, a reduction in delays in sleep onset, increased sleep duration and delayed waking

Anticonvulsant Mood & Behaviour Stabilisers: Carbamazepine,

sodium valproate, lamotrigine Excellent anticonvulsants with good safety profiles Proven track record for general adult mental health bipolar/cyclical mood disorders Emerging evidence base for child & adolescent fluctuating mood disorders Starting to be used experimentally for cyclical (and not so cyclical mood and behaviour challenges in children & young people with complex, multiple & severe developmental disabilities

Osunsamni & Turk, 2014: Influence

of age, gender & living circumstances on patterns of ADHD medication use in children & adolescents with & without intellectual disabilities

Aim:

to determine whether there are differences in psychopharmacological practice for ADHD in children and adolescents dependent on the presence or absence of associated intellectual disability; and if there are, whether the differences are influenced by factors such as age, gender and living circumstances.

Osunsamni & Turk, 2014: Younger

children with intellectual disabilities and ADHD were more likely to be established on non-stimulant medications than those with just ADHD and no intellectual disabilities

Conclusion:

being between the ages of 5 and 12 years as well as having intellectual disability and ADHD are associated with raised likelihood of being prescribed nonstimulant medications for ADHD. This difference is maintained irrespective of gender and living circumstances.

Targeted Medications mGlu5R GABAergics Glutamate

antagonists: e.g. mavoglurant

Lithium Minocycline Baclofen

& Arbaclofen

Rapamycin Statins

– tuberous sclerosis

– neurofibromatosis, Down Syndrome

ACAMH Occasional Papers No. 32 (2014)

Intellectual disabilities and challenging behaviour Edited by Mark Lovell and Orlee Udwin

Chapter Offprint

Chapter 4 Use of medication in children and young people with intellectual disability and challenging behaviours Jeremy Turk

How to Cite: Turk, J. (2014). Use of medication in children and young people with intellectual disability and challenging behaviours. In M Lovell & Udwin (Eds), Intellectual disabilities and challenging behaviour. ACAMH Occasional Paper 32 (Chap 4, pp. 36-44), doi:10.13056/OP32.g. London: Association for Child and Adolescent Mental Health

Full Book Publication Information: Table of Contents, Chapter Abstracts and doi information is available at: http://bit.ly/1wpw27E

Copyright © 2014 Association for Child and Adolescent Mental Health (ACAMH). All rights reserved. Published by Association for Child and Adolescent Mental Health (ACAMH), St Saviour’s House, 39/41 Union Street, London SE1 1SD, UK

Chapter 4

Use of medication in children and young people with intellectual disability and challenging behaviours Jeremy Turk Professor of Developmental Psychiatry, Institute of Psychiatry, University of London, and Consultant Child and Adolescent Psychiatrist, South London and Maudsley NHS Foundation Trust, London, UK Abstract  The modern use of psychotropic medications for psychological problems and challenging behaviours in children and young people with developmental disabilities is a growing field of research and clinical practice. Increasingly, these medications are being shown to complement psychological, educational and social interventions and supports in producing welcome and enduring benefits. They should always be used in addition to psychosocial treatments, as a means to an end, and never instead of these or as an end in themselves. Weighing up likely benefits against possible adverse effects is critical. The effective and safe use of these medications requires careful monitoring by suitably qualified clinicians. Treatment is usually of a symptom (e.g. aggression, self-injury or overactivity) rather than a syndrome (e.g. Down syndrome or fetal alcohol syndrome); although there is now increasing interest in targeted medications that may have actions specific to a particular condition such as fragile X syndrome, tuberous sclerosis or neurofibromatosis. Each prescription should take the form of a single-case open clinical trial, with the general tenet ‘start low, go slow’ regarding commencing dosage and rate of incremental increase in dose, which will be dependent on appearance of benefits and/or adverse effects. Adverse effects of medication are more common in individuals with developmental disabilities, emphasising the need for caution and monitoring. Even non-medically qualified child and adolescent mental health, and intellectual disability, clinicians need to be aware of, and have a basic knowledge of, this important and expanding field. Keywords  Children; adolescence; intellectual disability; challenging behaviour; psychopathology; medication Correspondence  Jeremy Turk, Southwark Child and Young Person Development Centre, Sunshine House, 27 Peckham Road, London SE5 8UH, UK; Email: [email protected] doi:10.13056/OP32.g

Key points Clinical practice: Medications can play an invaluable role in managing challenging behaviours and psychopathology in children and young people with intellectual and other developmental disabilities when combined with psychological, social and educational interventions and supports. Increasing numbers of medications are being identified as useful for specific symptoms, psychiatric disorders and challenging behaviours in this client group. Current research is identifying ‘targeted medications’ that act on neurochemical pathways thought to be relevant to specific syndromes and conditions. Increased central nervous system sensitivity in this client group means that lower than usual medication dosages are often indicated and that there is often a raised rate of adverse effects which need to be monitored for carefully and systematically. Knowledge of literature, specialist training and clinical experience are needed to undertake such treatments safely and effectively. Further research and practice development: Interactions and explorations of complementariness of psychopharmacological, psychological, social and educational combined treatments. Outcome medication studies focusing on moderate to profound intellectual disability populations. Further research into targeted medications for specific syndromes and conditions.

• • • • • • • • 36

ACAMH Occasional Paper 32: Intellectual Disabilities and Challenging Behaviour © 2014 Association for Child and Adolescent Mental Health. All rights reserved.

ACAMH Occasional Paper 32: Intellectual Disabilities and Challenging Behaviour

Key points (continued) Further research and practice development (continued): Incorporation of paediatric psychopharmacology for individuals with intellectual disability into higher child and adolescent psychiatry training programmes. Moves towards a paediatric developmental disability psychopharmacology expert in all child and adolescent mental health services.

• •

Introduction Problem behaviours occurring in children and young people who have intellectual disabilities can be divided into two groups. Firstly, there are those that affect the individual primarily. These include internalising disorders such as anxiety states, depression and phobias. These may often impact minimally on carers, even though their consequences for the quality of life of individuals concerned and their abilities to maximise their potentials may be severe. Secondly, there are those behaviours witnessed with increasing frequency and severity in individuals with diminishing intellectual ability, such as hyperactivity, aggression and self-injury. These behaviours impinge substantially on carers and others who would wish to help and support the individuals concerned. The behaviours characteristically present enormous challenges to carers and tend to be labelled ‘challenging behaviours’. Substantial progress has been made in understanding the origins of these behaviours as well as environmental factors which predispose to them and maintain their presence. Genetic factors certainly have a role to play. For example, the likelihood and nature of self-injury appears to be strongly genetically determined, with specific behavioural phenotype conditions (Mijovic & Turk, 2008) being associated with characteristic types of self-injury (Table 1). Certain behavioural phenotype conditions may also present with attention deficit hyperactivity disorder

(ADHD) (Turk, 2009). There are well-established genetic bases to ADHD and it occurs in individuals with intellectual disability more generally. The likelihood and intensity of ADHD increases with diminishing intellectual ability (Merwood & Asherson, 2011). Autism spectrum profiles also show genetic-syndrome-specific characteristics (Oliver, Berg, Moss, Arron, & Burbidge, 2011). Physical disorder and distress are further frequent causes of challenging behaviour in individuals with developmental disabilities and these should be investigated for and treated vigorously if found. For example, gastro-oesophageal reflux is very common in individuals with Cornelia de Lange syndrome, presenting with severe heartburn, which often triggers extreme self-injury as a means of counter-irritation (the self-injury is intended to relieve the heartburn), as well as hyperactivity (Luzzani, Macchini, Valade, Milani, & Selicorni, 2003). Speech and language challenges, and communication difficulties more generally, are additional common contributors to challenging behaviours in this client group (Taylor, 2008). However, by far and away the most common triggers, precipitants and perpetuating factors in the development and maintenance of challenging behaviours in individuals with intellectual disability are environmental and behavioural ones. Systematic evaluation for their presence, their nature and their role in producing and maintaining challenging behaviours by associative learning and reinforcement

Table 1  Genetic conditions and their characteristic forms of associated self-injury Genetic condition Lesch–Nyhan syndrome

Associated self-injury Knuckle gnawing, hand biting, lip biting

Key reference Robey, Reck, Giacomini, Barabas, & Eddey (2003) Cornelia de Lange syndrome Lip biting, head banging, hyperactivity Berney, Ireland, & Burn (1999) Fragile X syndrome Hand biting, especially over the base of the Symons, Clark, Hatton, Skinner, thumb in response to anxiety or excitement & Bailey (2003) Prader–Willi syndrome Skin picking and scratching, unpredictable Descheemaeker et al. (2002) and impulsive tantrums, gross compulsive over-eating Smith–Magenis syndrome Head banging, nail and tooth pulling, object Smith, Dykens, & Greenberg insertion into bodily orifices (1998) Cri-du-chat syndrome Head banging, head hitting, self-biting, Cornish & Bramble (2002) rumination 37

Turk: Use of medication in children and young people with intellectual disability and challenging behaviours schedules should be mandatory in clinical practice, as a means of identifying their existence and hence developing an appropriate behaviour modification strategy to ameliorate them (Clements & Martin, 2002). Nonetheless, it is often the case that psychological approaches alone may be insufficient to bring about desired improvements in challenging behaviour. Reasons for this are listed in Box 1.

A number of general principles apply irrespective of the medication being considered. These are listed in Box 2. Box 2  General principles guiding the use of medication for challenging behaviours in children and young people with intellectual disabilities Medication should never be the initial intervention. Consider psychological, educational, family and social approaches first. If these are insufficient then consider the cautious addition of medication while maintaining the other approaches. Thorough multidisciplinary assessment must be undertaken as a preliminary to any prescription. Treat symptoms (e.g. aggression, overactivity, self-injury) not a syndrome (e.g. autism) or an underlying condition (e.g. fragile X syndrome). Undertake a clinical trial of medication. Does it work or not? Are there side effects? Consider the cost-benefit ratio. What is the likelihood of improvement? How important is this? What is the likelihood of side effects? How serious might they be? Beware of the increased risk of side effects in people with intellectual disability and neurodevelopmental disorders. If medication is ineffective, stop it! If medication does work, give it for the minimum time possible with frequent monitoring and reviews regarding continuing need and possible side effects. Do not ask whether medication works for people with a particular condition. Ask whether a specific medication may work for a specific behavioural problem.

•

Box 1  Reasons for behavioural approaches being unusable or insufficient (Turk, 2010a) It may be impossible to prevent the contingent presentation of the reinforcer (simultaneous occurrence of rewarding action in response to an individual’s challenging behaviours); for example, self-injury is so intense that to ignore it would be tantamount to clinical negligence. It may be undesirable to withhold the contingent reinforcer for practical reasons; carers are willing and able to ignore aggression but its consequences for property and other individuals may be unacceptable. There is often a transient initial increase in the rate of the undesirable behaviour – the so-called extinction burst. This may make the programme inappropriate or dangerous (e.g. it may be considered unsafe to risk a seriously head-banging child increasing the behaviour, however temporarily). It may take too long; carers give up ignoring their child’s eye poking after 3½ hours and go and comfort her, thereby conveying the message that longer periods of self-injury are necessary to get carer attention, even if the response is not immediate. There may be other practical concerns such as a lowered seizure threshold in a child prone to epilepsy who is emotionally aroused. Behavioural and other psychological approaches may have been tried yet found to be insufficient to produce adequate improvement. Relevant professional support may simply not be available.

•

•

• •

•

• •

•

• • •

•

•

• •

Generally, medication dose will be determined by body weight. However therapeutic dose levels vary substantially, depending on a number of factors including degree and timing of gastrointestinal absorption, level of first pass hepatic metabolism, ability to cross the blood brain barrier, central nervous system receptor sensitivity and synaptic factors including neurotransmitter reuptake and post-synaptic cascade pathways. Psychotropic medications are often not licensed for children and young people and are rarely licensed for individuals with developmental disabilities. However, this does not mean that they cannot be prescribed. In fact many are relatively safe and potentially highly beneficial (Bernard & Turk, 2009). Medication may be useful for: hyperactivity and attention deficit disorders; self-injurious behaviour;

•

In such situations it is reasonable, ethical and humane to consider the addition of medication to the already active package of psychological, educational and social interventions and supports, as a means to an end rather than as an end in itself. The hope is that by opening a window of therapeutic opportunity, psychosocial treatments will stand a better chance of succeeding, thereby allowing the medication to be withdrawn in the longer term.

• • 38

ACAMH Occasional Paper 32: Intellectual Disabilities and Challenging Behaviour

• aggression and violence; • sleep disorders, • mood disorders; • anxiety disorders such as obsessive–compulsive

recognition of suicidal ideation and behaviour (Wooltorton, 2005). The possibility of cardiovascular adverse effects has been raised but evidence for these remains inconclusive (Stiefel & Besag, 2010). As yet there is no scientific data on its usage with children and young people who have intellectual disability. The main other medication option for ADHD in children and young people with intellectual disability is the α2 agonist clonidine (Ingrassia & Turk, 2005). Clonidine is of particular use where evening and bedtime settling, and repeated night-time waking, are problematic or where attentional deficits and overactivity coexist with Tourette’s syndrome or other tic disorders. Clonidine does not affect appetite. It can be prescribed as an adjunct to stimulant medication, providing cardiovascular status is normal. Adverse effects include sedation, cognitive blunting and hypotension. Dosage commences at 25 micrograms twice daily, increasing in 25 microgram twice daily increments up to a maximum of approximately 150 micrograms twice daily dependent on clinical response and adverse effects. Decisions regarding which medication to prescribe for ADHD features should be based on: presence of co-morbid conditions, e.g. tic disorders, Tourette’s syndrome, epilepsy; different side-effect profiles of the drugs; compliance issues, e.g. midday treatment doses at school; drug diversion and/or misuse; individual preference; cost (if there is a choice).

disorder.

Attention deficit hyperactivity disorders The mainstay of medication treatments for ADHD are the psychostimulants, in particular methylphenidate. Benefits for young people with intellectual disability who have ADHD have been confirmed (Pearson et al., 2004a, 2004b). Very low starting dosage is advisable because of increased central nervous system neurosensitivity in immature or atypically developing brains. By the same token, unusual or idiosyncratic adverse effects are relatively common. Possibly the most common undesired effects are lack of response and paradoxical excitation – the ADHD features becoming accentuated rather than diminishing. These adverse effects resolve following medication discontinuation. Other potential adverse effects include appetite suppression with weight loss, sleep disturbance with difficulty settling to sleep at night, abdominal pain, headaches, dizziness and light-headedness, anxiety and agitation, unmasking of tics and nervous twitching, mood lability, reversible growth restriction, pulse rate and blood pressure increases, and lowering of seizure threshold. All these possible adverse effects should be monitored for carefully and regularly, along with regular measurements of pulse, blood pressure, height and weight. Immediate release preparations usually require morning and lunchtime dosing because of the medication’s short half-life. To avoid insomnia, the final dose should be given around the middle of the day. Modified release preparations bring the potential benefit of once daily morning dosing. For individuals who find swallowing a whole tablet such as Concerta XL difficult, it is possible to prescribe modified release capsules such as Equasym XL and Medikinet XL which allow for the capsule to be broken and the granules sprinkled on food. Dexamfetamine may be considered as an alternative to methylphenidate although adverse effects to one usually predict similar outcomes with the other. Starting immediate release dosage is usually 5 mg mornings and lunchtimes, increasing in 5 mg twice daily increments. Maximum dosage required is usually not in excess of 20 mg twice daily, though higher doses may occasionally be required. Some clinicians advocate three times daily dosage as the child grows older, bed time becomes later and hence concentration is required for longer during evenings. Atomoxetine, a selective norepinephrine reuptake inhibitor, is often considered as a second-line agent because it lacks sleep and appetite adverse effects (Barton, 2005). However, sedation and nausea have been reported as have liver toxicity and the more recent

• • • • • •

There are a number of myths regarding the prescribing of medication for ADHD in children and young people with intellectual disability. Firstly, it is not the case that overactivity, inattentiveness and impulsiveness are to be expected in children with intellectual disability. These tendencies are common and debilitating, and compound the developmental constraints produced by the underlying intellectual and other developmental disabilities. However, they are often eminently treatable, psychologically (Turk, 2004) as well as medically. Secondly, it is quite possible (albeit relatively more complex) to diagnose ADHD in a young person with intellectual disability. Response to medication is often gratifying and free of side effects. It is also worth noting that situationality of challenging behaviours does not exclude a diagnosis of ADHD. Individuals with ADHD will still tend to have their behaviours influenced by setting, those present, what is happening and how they are responded to. Different environments will affect behavioural tendencies differentially, and different informants may interpret and report behaviours differently. The tolerability of behaviour in different environments (e.g. school versus home) may vary as may the relative prominence of behavioural versus cognitive features. Finally, the conduciveness of the individual’s immediate

39

Turk: Use of medication in children and young people with intellectual disability and challenging behaviours surroundings and environment, and the empathy of others to the individual’s predicament will vary as well.

(Hassler & Reis, 2010). Atypical antipsychotics, in particular risperidone, are prescribed (Shea et  al., 2004). Aripiprazole is sometimes considered if weight gain or sedation become an issue. However, combining antipsychotics runs the risk of serious complications including neuroleptic malignant syndrome. Anticonvulsants, antidepressants and anxiolytics are also prescribed for aggression. Evidence for sodium valproate and other anticonvulsants being beneficial in treating aggression is at best equivocal (Huband et al., 2010). Some evidence supports the use of the SSRI antidepressants (Janowsky et  al., 2005). Buspirone is also reportedly useful in decreasing aggression, particularly in relation to arousal and anxiety (Ratey et al., 1991).

Self-injurious behaviour Self-injurious behaviours can be severe, debilitating and even life threatening (Oliver & Richards, 2010). While behaviour modification approaches remain the mainstay of treatments, medications have an important role, particularly where the self-injury is serious, protracted and resistant to psychosocial interventions alone. Neurochemical hypotheses centre largely on the roles of dopamine, serotonin and endogenous opioids (King, 2000). There are three main biomedical models for self-injury, each with its corresponding medication implications. Pain behaviour, including reactions to pain, appears to be associated with self-injury, with implications for endorphin theories. In this model self-injury is postulated as triggering the release of endogenous opioids which produce pleasurable sensations that are intrinsically positively reinforcing. It therefore follows that application of an opioid antagonist, such as naltrexone, will extinguish pleasurable sensations, producing aversive pain as the consequence of self-injury, which should reduce the frequency and intensity of target behaviour (Symons, Thompson, & Rodriguez, 2004). A second model of self-injury frames it as a tic disorder with corresponding anti-tic medications being proposed. Butyrophenones such as haloperidol tend not to be prescribed because of their high rates of acute dystonias, tardive dyskinesia and withdrawal emergent phenomena. More often clonidine, for milder cases, and risperidone are tried. The evidence base remains sparse though there is the suggestion of risperidone being beneficial for self-injury in adults with intellectual disability (Cohen et  al., 1998) and for autism spectrum conditions (MacCracken et al., 2002), as well as for children with Down syndrome, severe intellectual disability and autism spectrum conditions (Capone et al., 2008). The third biomedical model conceptualises self-injurious behaviour as a form of obsessive–compulsive disorder. Witnessing the seemingly compelled behaviour of sufferers and the clear egodystonic nature of the self-injury in these situations certainly supports this proposition. On this basis anti-obsessive agents such as clomipramine, or selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine or sertraline are sometimes prescribed (Janowsky et al., 2005).

Sleep disorders Sleep disorders are extremely common in children and young people with intellectual disability, produce considerable challenges for parents and other carers, and lead to substantial and multiple co-morbidities (Turk, 2010a; Turk, 2010b). Sleep disorders can take many forms including sleep onset (induction) difficulties, repeated night-time waking, early morning waking, sleep apnoea, periodic limb movement disorder, excessive daytime sleepiness, anomalous and disrupted sleep-wake cycles, and parasomnias including nightmares, night terrors, sleep talking and sleepwalking. Quine’s longitudinal study of sleep disturbance in 200 young people with moderate to profound learning disability identified 51% of them as having settling problems, 67% of them as having waking problems and 32% of their parents as reporting rarely getting enough sleep. She found in the study population that child sleep disturbance was associated with the learning-disabled child having poor communication, poor academic and self-help skills, incontinence, daytime behaviour problems, epilepsy, cerebral palsy and other ‘named conditions’ (such as tuberous sclerosis) with the exception of Down syndrome. These children’s parents reported substantial rates of stress and irritability. Conversely, Quine found no statistical association between sleep disturbance in these children and family variables, namely social class, income, family composition and housing tenure. She concluded that the families containing children with severe sleep difficulties frequently had many other problems of family functioning. However, she noted that the direction of causality in this association is all too often mistaken, with family dysfunction and parental psychological disturbance viewed as the cause rather than the consequence of severe childhood sleep disorder (Quine, 1991). For night-time settling and sleep induction difficulties there is now accumulating evidence for the benefits of melatonin supplementation (Turk, 2003; Braam et al., 2009). As well as decreasing sleep latency, Braam et al. (2009) concluded that melatonin also reduces number of wakes per night and increases total sleep time. Initial

Aggression Aggression, frequently unfocused, chaotic, disorganised, sporadic and seemingly spontaneous, is a further common extremely challenging behaviour witnessed in individuals with moderate-to-profound intellectual disability. Medication is often resorted to where the behaviour is extreme, persistent, dangerous and unresponsive to psychological and social interventions and supports 40

ACAMH Occasional Paper 32: Intellectual Disabilities and Challenging Behaviour dosage is usually 1–3 mg, 20–30 minutes before desired sleep, with the potential to increase in 0.5 mg increments using liquid preparations to enable such small dosage increases. Tolerance and habituation have been reported but these usually respond to drug holidays. Oral synthetic melatonin frequently produces marked and welcome improvements in even extremely long-standing and severe sleep disturbance in children and young people with serious and often multiple developmental disabilities. Therapeutic dose does not appear to be predicted by severity of sleep disturbance, severity of intellectual disability or presence/absence of an autism spectrum condition. A number of explanations exist as to why exogenous melatonin supplementation should be beneficial. Some individuals may have insufficient melatonin synthesis and secretion, while others may lack the diurnal secretion rhythm. Receptor insensitivity is a further possible contributor. Cortical blindness and cerebral palsy may also be associated with exogenous melatonin benefits. A controlled release preparation of melatonin (Circadin®) is available and has recently been subjected to a randomised, double-blind, placebo-controlled crossover trial (Wasdell et al., 2008). However, a direct comparison of controlled-release versus standard-release melatonin has not been undertaken, making it impossible to conclude whether the controlled-release version provides meaningful benefits and added value over the immediate release one. There has also been interest in the use of melatonin antagonists such as the selective beta-1 adrenergic antagonist acebutolol (De Leersnyder et al., 2003). However, these have yet to be used widely in clinical practice; the research having focused largely on Smith–Magenis syndrome which is thought to be associated with a specific impairment of the melatonin circadian secretion cycle. Clonidine may be beneficial for repeated night-time waking, particularly where an evening calming effect is desired and where sleep disturbance coexists with ADHD or tic disorders (Ingrassia & Turk, 2005). In these situations a single evening dose of between 25 and 100 micrograms may be indicated. Other hypnotics and sedatives such as benzodiazepines, antihistamines and chloral preparations have often been tried but the evidence base for their use is extremely limited.

with no effect on appetite. It is already used widely as a treatment for cyclical mood disorders in adults as well as children and young people. There is growing anecdotal evidence that it can also be a good mood and behaviour stabiliser in not-so-cyclical challenging behaviours in children and young people with intellectual disability. Findings from a single-person study design (Turk, 2010c) suggested clinically significant improvements in disruptive behaviours, self-absorption, anxiety and autistic tendencies as well as reduced overactivity, inattentiveness and oppositionality. The quality of life of the child and parents also appeared to have been enhanced substantially.

Depression Depressed mood will tend to present in young people with moderate-to-profound intellectual disability as tearfulness, apathy, social withdrawal and behavioural change in the presence of the so-called biological features of diminished appetite and sleep disturbance. Extrapolations from adult literature suggests that such happenings, often associated with the development of challenging behaviours, frequently follow a stressful life event such as bereavement (Dodd, Dowling, & Hollins, 2005) and post-traumatic stress disorder (Turk, Robbins, & Woodhead, 2005). Psychological therapies and social interventions should always be the first strategies to be used. Where necessary, anecdotal evidence supports the use of SSRIs such as fluoxetine. These medications also have useful anxiolytic and anti-obsessive qualities. Fluoxetine is available as a liquid preparation with a concentration of 4 mg/ml. In young people with complex, severe and multiple disabilities, commencing with the minimum dosage of 4 mg daily and increasing cautiously in 4 mg increments up to a maximum of 20 mg daily may be indicated. However, benefits may take 6–8 weeks to develop. There is a lack of an evidence base, findings from studies of normally developing children and young people being extrapolated to this population. Research on the use of SSRIs for adults with intellectual disability and perseverative and maladpative behaviours suggests only a third or so benefit (Branford et al., 1998).

Anxiety Medication has a more limited role in the treatment of anxiety, which should primarily be psychological. Benzodiazepines and barbiturates should not be prescribed because of their side effects, of tolerance, addiction and respiratory depression. SSRIs such as fluoxetine and sertraline are sometimes used as are serotonin and norepinephrine reuptake inhibitors such as venlafaxine, with some research evidence for their benefits in adults with intellectual disability (Cooray & Bakala, 2005). In extreme circumstances a time-limited trial of a low dose atypical antipsychotic may be justified.

Mood disorders There is increasing evidence of benefits of anticonvulsants in cyclical mood disorders in children and young people (Danielyan & Kowatch, 2005). There is some support for their use for challenging behaviour in adults with intellectual disability (Deb et al., 2008) though methodological constraints make firm conclusions difficult to draw. Carbamazepine is a well-established and generally well-tolerated anticonvulsant. It is usually non-sedating 41

Turk: Use of medication in children and young people with intellectual disability and challenging behaviours

Novel medications

targeted, interventions is complex. However, awareness of the developing potential to focus medication on condition-specific, neurochemical deficits and imbalances allows for hope that biomedical treatments for developmental disabilities may be a real possibility rather than merely a dream.

Current research is starting to focus on specific receptor anomalies relating to particular genetic and other conditions as a means of identifying and developing more targeted drug interventions. For example, the immunosuppressant rapamycin, and other agents that act on the mammalian target of rapamycin receptors (mTOR), appear to benefit individuals with tuberous sclerosis through its actions on post-synaptic cascade pathways, whereby cerebral tuber shrinkage can be dramatic (Franz et al., 2006). In fragile X syndrome, the most common identifiable inherited cause of intellectual disability and autism spectrum conditions (Turk, 2011), pharmacologically promising developments are based on our recently developed awareness of the importance of the glutamate-GABA synergistic neurotransmitter systems in maintaining psychological stability and balance in many ways, and in particular the relevance of the postsynaptic metabotropic glutamate receptor 5 (mGluR5) pathways for fragile X syndrome (Jacquemont et al., 2011; Michalon et al., 2012). GABAergic agents (Heulens, D’Hulst, Braat, Rooms, & Kooy, 2010), and by implication glutamate antagonists, are revealing promising findings in scientific laboratory, small mammal and preliminary human studies. These agents include a range of already available and frequently prescribed products including lithium salts (Liu, Chuang, & Smith, 2011), minocycline (Paribello et al., 2010) and baclofen (Hagerman, Lauterborn, Au, & Berry-Kravis, 2012). Currently, such neurochemical modes and research findings are promoting discussion regarding the possibility of making in-roads in to the features of autism spectrum conditions more generally (Hampson, Adusei, & Pacey, 2011). The underlying neurophysiology and neurochemistry of these novel,

Conclusion Medication has an increasing role in the management of psychological challenges, psychiatric disorders and challenging behaviours in children and young people with intellectual disabilities. However, psychotropic medications are frequently unlicensed for such indications and the evidence base for their use is limited. Nonetheless, the judicious use of modern medications that target specific symptoms or behaviours can often produce impressive improvements when prescribed in association with psychological, educational and social interventions and supports. The high rates of side effects, attributable to heightened central nervous system sensitivity, mean that treatments need to be overseen by highly specialist, experienced and competent clinicians. Our understanding of the underlying neurological and neurochemical bases of many conditions causing developmental disabilities is increasing. So too are the possibilities for further substantial benefits from psychotropic medication for this client group.

Acknowledgement This contribution was invited for this publication and is based on presentations made at various conferences, including the ACAMH conference on Child and Adolescent Learning Disabilities. The author has declared that he has no competing or potential conflicts of interest in relation to this article.

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