Case 11 – The Spectrum Disorders – From Autism to OCD notes PDF

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Case 11: The Spectrum Disorders – From Autism to OCD Case 11 – The Spectrum Disorders – From Autism to OCD Page 1 of 28 Case 11: The Spectrum Disorders – From Autism to OCD Case Introduction  Learning disability  A significantly reduced ability to understand new or complex information or learn new...

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Case 11: The Spectrum Disorders – From Autism to OCD

Case 11 – The Spectrum Disorders – From Autism to OCD

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Case 11: The Spectrum Disorders – From Autism to OCD

Case Introduction 

Learning disability  A significantly reduced ability to understand new or complex information or learn new skills (impaired intelligence) with a reduced ability to cope independently (social function) which started before adulthood, with a lasting effect on development

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What is not a learning disability  Problems with reading, writing or numeracy only = learning difficulties  Emotional difficulties  Always linked to conditions like Attention Deficit Hyperactivity Disorder (ADHD)  Asperger’s syndrome and some individuals with Autism Autism Spectrum Disorder (ASD) = a lifelong developmental disability that affects how a person communicates with, and relates to, other people It also affects how they make sense of the world around them Causes of autism  Genetic influences are likely most important risk factor – but not the only cause  Cause is likely to be multifactorial  Physiology and environment are always interacting from day 1  May be several types of autism with different causes

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Characteristics of Autism – people with autism generally experience three main areas of difficulty 1. Social communication 2. Social interaction 3. Social imagination Social communication – social communication is where people with autism have difficulties understanding: Page 2 of 28

Case 11: The Spectrum Disorders – From Autism to OCD

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 Facial expressions  Tone of voice  Common gestures  Eye contact  Body language Social interaction – social interaction is where people with autism struggle with:  Understanding their own and other people’s feelings and emotions  Forming relationships and making friends  Can appear aloof, indifferent and withdrawn Social imagination – social imagination is where people with autism have difficulties comprehending:  Abstract concepts and ideas  People’s actions, emotions, behaviours and consequences  Solutions to life outside their routines

Epidemiology and Presentation of ADHD      

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ADHD is a heterogeneous behavioural syndrome characterised by the core symptoms of hyperactivity, impulsivity and inattention While these symptoms tend to cluster together, some people are predominantly hyperactive and impulsive, while other are principally inattentive Symptoms of ADHD can overlap with symptoms of other related disorders and ADHD can’t be considered a categorical diagnosis – therefore a differential diagnosis is needed Common co-existing conditions in children with ADHD are disorders of mood, conduct, learning, motor control, communication and anxiety disorders In adults, they include personality disorders, bipolar disorder, OCD and substance misuse Clinical background – the DSM-V diagnosis of ADHD:  Extremes of the triad symptoms of inattention, impulsivity and hyperactivity behaviour  These are:  Pervasive  Of early onset  Unexplained by other disorders  Resulting in impairment and disability The ICD-10 hyperkinetic disorder is more restrictive and requires symptoms to be more:  Pervasive  Impairing Diagnostic criteria od ADHD according to the ICD-10  Inattention  Overactivity  Impulsiveness  Most occur from an early age  Persist in more than 1 setting  Impairment in social functioning, learning and normal development Guidelines from the American Academy of Paediatrics (AAP): Page 3 of 28

Case 11: The Spectrum Disorders – From Autism to OCD  

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The diagnosis is based on very specific symptoms, which must be present in more than 1 setting Children should have at least 6 attention deficit symptoms or 6 hyperactivity/impulsivity symptoms with some symptoms presenting before the age of 7 The symptoms must be present for at least 6 months, seen in 2 or more settings, and not caused by another problem The symptoms must be severe enough to cause significant difficulties in many settings, including home, school and in relationships with peers

Inattentive symptoms  Fails to give close attention to details or makes careless mistakes in schoolwork  Has difficulty keeping attention during tasks or play  Doesn’t seem to listen when spoken to directly  Doesn’t follow through on instructions and fails to finish schoolwork, chores or duties in the workplace  Has difficulty organising tasks and activities  Avoids or dislike tasks that require sustained mental effort e.g. schoolwork  Often loses toys, assignments, pencils, books or tools needed for tasks or activities  Is easily distracted  Is often forgetful in daily activities Hyperactivity symptoms  Fidgets with hands or feet or squirms in seat  Leaves seat when remaining seated is expected  Runs about or climbs in inappropriate situations  Has difficulty playing quietly  Is often “on the go” acts as if “driven by a motor” talks excessively Impulsivity symptoms  Blurts out answers before questions have been completed  Has difficulty awaiting turn  Interrupts or intrudes on others – butts into conversations or games ADHD is a chronic condition It commonly continues through adolescence and then into adulthood (with consequent high co-morbidity of depression and anxiety If untreated, can be associated with:  Educational difficulties  Employment difficulties  Relationship problems  High incidence of substance misuse – most commonly alcohol and/or cannabis

Management  Diagnosis must follow extensive and comprehensive mental health assessment by a specialist clinician:  Paediatrician  Child psychiatrist Page 4 of 28

Case 11: The Spectrum Disorders – From Autism to OCD In addition, the diagnosis should follow a full assessment by an educational and/or clinical psychologist Onset – usually before aged 3 years, often some symptoms arise in infancy Duration – 6 months and to a maladaptive level inconsistent with normal development Severity – clinically significant severity in at least 2 different settings

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Non-pharmacological interventions  Psycho-educational measures – education and advise should be the basis of any treatment offered  Parent training and family-centred behavioural therapy  Behavioural interventions (school or pre-school) – effective in reducing hyperactive behaviour and promoting social adjustment Treatment  With pharmacological treatment of ADHD, most medication is used for symptoms rather than the cause  Experimental studies are difficult to conduct in terms of ethics and practicality  Pharmacodynamics and pharmacokinetics have been extrapolated from adult studies, therefore:  Off-licence, beyond terms of licence  Must discuss openly and fully with carers (and patients if appropriate)  Obtain informed consent  Don’t assume that drugs are necessarily more hazardous at the younger end of the spectrum  Bioavailability is often lower in children due to:  Rapid metabolism  Distribution in a relatively larger ECF (extracellular fluid)  Drugs cross the blood brain barrier more readily  Prescribing and subsequent titration should be on a mg/kg dosing range

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Ideal properties of medication used in the treatment of ADHD:  Longer duration of action  Not potentially addictive  Ease of administration  Absence of rebound effects  No effect on appetite growth  Rapid onset of action  Effective in treating associated symptoms e.g. depression, anxiety  Dissipates rapidly – hence will not induce insomnia

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Pharmacological treatments  Psychostimulants  Methylphenidate  Dexamphetamine  Centrally-acting sympathomimetics, Atomoxetine, should only be used after:  Specialist assessment Page 5 of 28

Case 11: The Spectrum Disorders – From Autism to OCD And as part of a care package that includes: o Educational o Psychological o Behavioural assessment + intervention Stimulants  Stimulants are effective in at least 70% of hyperactive children  Dysfunctional dopamine pathways (decreased dopaminergic activity) in the frontobasal ganglia are thought to be responsible for the clinical symptoms of ADHD  They are more effective in treating hyperactivity than inattention, however, still need to improve:  Attention span  Impulsivity  Aggression  Social Interaction  Social skills and general academic achievement may not improve Methylphenidate  Licensed for ADHD as part of a comprehensive treatment programme  Reserved for when remedial interventions have not been effective/proved suboptimal  Patient must be under specialist supervision  Not licensed in children under 6 years old  Mechanism of action  Inhibits the uptake of monoamines into the presynaptic neurone, thereby increasing dopamine hit as post-synaptic receptor sites  Dosing schedule  Initially 5-10mg OD/BD  Increase weekly by 5-10mg to a maximum 60mg daily in divided doses  If no response after 1 month at maximal dose, and with assured compliance, then stop treatment  A modified release preparation, Concerta XL 18mg, 36mg, was licensed – enhances compliance and may reduce rebound effects via smoother kinetics hopefully minimising peaks and troughs Side effects of stimulants  Insomnia  Decreased appetite  Euphoria/depression/anxiety  Psychosis (rare)  Hepatic dysfunction and blood dyscrasia have been reported with methylphenidate  Stimulate use should be proactively assessed and the drug should be withdrawn periodically for 1 months for a drug-free assessment  The stimulants are usually withdrawn during or after puberty 

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Dexamphetamine  Licensed for children 3 years and over  Mechanism of action

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Case 11: The Spectrum Disorders – From Autism to OCD Dexamphetamine increases the release of monoamines (including dopamine) into the synaptic cleft, as with methylphenidate pharmacological efficacy centres on increasing post-synaptic dopamine receptor occupancy Dosing schedule  Initiate at a dose of 2.5mg-10mg depending on age  Increase dose by 2.5mg weekly  Maximum dose of 20mg  Off-licence dosing may go as high as 40mg

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Atomoxetine  Used for children over 6 years old and adolescents and adults  Mechanism of action:  Highly selective inhibitor of the pre-synaptic noradrenaline transporter  Minimal effect on serotonergic or dopaminergic transporters  Atomoxetine isn’t a psychostimulant, nor an amphetamine derivative and has limited abuse potential  Dosing schedule:  Children 70kg – initiate at 40mg, titrating after 7 days to 80mg as maintenance  Adults – initiate at 40mg, titrate to 80-120mg

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Psychological response assessed by the use of appropriate rating scales e.g. Connors abbreviated scale The be completed regularly and systematically in different settings:  School – educational psychologist  Home – parents

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Monitoring  Methylphenidate  Height, weight, body mass index  Baseline and 6 monthly full blood count and liver function test  Annually, withdraw over 1 month  Long-term aim/therapeutic goal – maintain medication until the child’s maturation and learning of cognitive skills render medication unnecessary  Atomoxetine  On initiation, observe for agitation, irritability, suicidal thinking and self-harming behaviour – also be alert to this after a change in dose  Monitor also hepatic function  Warn patients/parents/carers – abdominal pain, dark urine, pale stools, unexplained nausea, malaise and jaundice

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Other pharmacological agents used in ADHD  TCA’s (Imipramine) at 1mg/kg – lower dose, faster onset (3-4 days) than for depression  Clonidine – slight positive effect on hyperactive behaviour, no/little effect on cognitive performance

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Risperidone – some effect vs hyperactivity but risk:benefit ratio isn’t favourable (not recommended by NICE) Bupropion – a noradrenaline and dopamine re-uptake inhibitor Modafinal – a psychoanaleptic – centrally-acting sympathomimetic

Summary  MDHT (multi-disciplinary healthcare team) approach in ADHD is essential – paediatricians, psychiatrists, pharmacists, psychologists etc.  Pharmacological agents are a part, only in an integrated, holistic treatment modality  Psychostimulants remain first-line drug treatments  Regular monitoring and drug-free assessments should be an integral part of the care package

Treatment of ADHD

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Epidemiology  ADHD requires the onset of symptoms to be before aged 12 years  Inattentive symptoms are more likely to persist into adulthood  The combined subtype and a higher prevalence of ADHD is seen with boys – 3-4 times greater compared to girls  ADHD behaviours could be caused by or certainly compounded by mood, anxiety and sleeping disorders  Adults with ADHD are more likely to have been arrested, to be divorces or separated, have been diagnosed with a STD and be unemployed

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ADHD medications

Stimulants  Dexamphetamine – dopamine re-uptake blockade, presynaptic release  Methylphenidate – dopamine re-uptake blockade Non-stimulants  Atomoxetine – noradrenaline re-uptake inhibitor Page 8 of 28

Case 11: The Spectrum Disorders – From Autism to OCD 

Guanfacine (alpha 2A agonist) – modulates signalling in the pre-frontal cortex and basal ganglia through modification of direct synaptic noradrenaline transmission via alpha 2A agonist receptor agonism

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Neurobiology and MOA of ADHD  ADHD is associated with dysfunctional cortico-striatal-thalamic-loops  Results in dysfunction of catecholamine transmission – noradrenaline and dopamine  Delayed brain growth, smaller basal ganglia, cerebellum and frontal lobes have all been detected on MRI scans on patients with ADHD

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Side effects  Stimulants  Appetite suppression  Weight  Irritability  Anxiety  Headaches  Sleep disorders  Dysphoria  BP changes  Non-stimulants  Dizziness  Drowsiness  Dyspepsia  Decreased appetite  Hypotension  Bradycardia

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Monitoring  Monitor efficacy by using an accepted rating scale e.g. Conner’s rating scale  Monitor growth – height, weight and BMI, sleep charts, cardiac function  Take care with Guanfacin – monitor QTc2 prolongation These almost universally occur  Be alert to rare psychotic side effects with the stimulants only and  Hallucinations mostly visual hallucinations  Mania-type symptoms occur Titration  Start low and go slow  Keep going until the optimal risk/benefit ratio is established  In clinical practice, identify a regular activity that requires concentration during a time when the medication is active – then closely monitor the effect when the medication is titrated

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Common prescribing errors  Failure to increase dose slowly until no further improvements are noted or side effects are manageable  Beginning with an initial dose that is too high

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Case 11: The Spectrum Disorders – From Autism to OCD 

It’s often observed in clinical practice that the duration of effect is either longer or shorter than that reported in the literature

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Special considerations when prescribing for adolescents  See adolescents alone  Tailor treatment to their needs and concerns  Review side effects, signs of overmedication and under medication  Drug interactions  Driving risks  Sexual behaviour risk taking  Empower adolescents – give them more control over their treatment  When prescribing stimulants, low amounts is often the best defence vs misuse/diversion

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Co-morbid psychiatric problems  Major depression  Treat the most impairing disorder first  Moderate to severe depression – pharmacological interventions are first-line  Consider the risk of suicidality, suicide ideation, akathisia with SSRIs and SNRIs  With dysthymia (persistent mild depression) – treat ADHSD first, mood may then improve  Consider bupropion and desipramine – may reduce ADHD symptoms but with a reduced effect size compared to psychostimulants  Bipolar disorder  Treat bipolar disorder  Treatment of ADHD can be offered when bipolar disorder is stabilised – refer to specialist  Pharmacological treatment of BPAD is complex, various sub-set presentations exacerbate the complexity – refer to BPAD presentation  Anxiety disorders  This would include GAD, panic disorder, social phobia, OCD, PTSD  Treat the most impairing order first  Some patients may show worsening of anxiety and some may improve  ADHD treatments can be less well tolerated in this patient population  Start low and go slow  Consider switch to atomoxetine

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Psychotic disorders  Treat psychotic disorders first  Treatment of ADHD can trigger a psychotic relapse in a predisposed patient  Stable patients who are in remission (from psychosis) may benefit from ADHD treatment

Paediatric Formulations Page 10 of 28

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Preterm/neonates’ dosage forms and routes  Drug administration by injection  Suppositories  Enteral feeding tube Enteral feeding tube drug administration potential problems  Physical/chemical interactions with feeds/other drugs  Interaction with delivery device  Possible decreased serum drug concentrations  Amiodarone  Certain PPIs

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Infants dosage forms and routes  Drugs administered via oral route by syringe or added to drink  Liquids e.g. suspensions

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Children dosage forms and routes  Liquids e.g. suspensions  Depends on:  Size and shape tablet  Taste of alternative  Delayed in certain conditions

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Difference between licensed, off-label and unlicensed use  Licensed use – a medicine which has a product license where the product license cover the indication for which the medicine is being used for  Off-label use – a medicine with a product license where the product license doesn’t cover the indication for which the medicine is being used  Unlicensed use – a medicine with no marketing authorisation for any indication

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A licensed drug is used off-label when it’s used:  By an unlicensed route  For an unlicensed indication Page 11 of 28

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At an unlicensed dose Outside stated age limits Contraindicated in children

Unlicensed medicines include:  Unlicensed dosage form e.g. crushing tablets  Unlicensed drug – new medicines  Imported medicines Manipulation of adult dosage forms  Crushing tablets  Opening capsules and mixing the content with food or drink  Halving or quartering tablets  Diluting concentrated liquid preparations  Cutting or halving suppositories Problems of manipulating adult formulations  Increased risk of error  Increased risk of side effects  Issues with supply  Child refusal Varying needs Page 12 of 28

Case 11: The Spectrum Disorders – From Autism to OCD Pharmacokinetic variations with age  Potentially different doses for different ages  Dose calculated upon body mass  Requirement of measurable doses  Taste issues  Formulation preferences for different ages  Limited enrolment in trials – a serious issue and results in an inability to demonstrate efficacy and safely in all children (results can be extrapolated from adult...