Dementia- What not to forget!

Dementia-What not to forget! Ishbel McCallum Mental Health Pharmacist NHSGG&C Karen Liddell Mental Health Pharmacist NHS Ayrshire & Arran May 2014

Session Structure • Dementia overview • Diagnosis, assessment, differential diagnosis • Treatment – acetylcholinesterase inhibitors • Treatment – memantine • Treatment of BPSD • Discontinuing treatment • End of life issues

What is Dementia? Evidence of a decline in memory and thinking which is sufficient to impair functioning in daily living, and often changes in social behaviour, present for 6 months or more

Symptoms • Memory problems • Difficulty managing day to day tasks • Difficulty communicating • Changes in mood, judgement or personality • Disorientation • Impaired learning • Impaired reasoning

Types of dementia

Alzheimer’s disease • Damaged tissue builds up in the brain to form deposits called ‘plaques’ and ‘tangles’, causing the brain cells around them to die. • Reduction in Acetylcholine • Gradual onset affecting first memory and then global cognitive impairment. • Decline is slow and progressive. • Average survival period from diagnosis is 7 to 10 years. • Evidence of cerebral atrophy (more marked in temporal lobe) as the illness progresses.

Vascular dementia • More abrupt onset. • Stepwise deterioration. • Periods of acute confusion • History of vascular risk factors: hypertension, smoking, heart disease, diabetes,… • Speech difficulties • Cerebrovascular disease in CT and EEG. • Depression can be quite common

Dementia with Lewy Bodies • Vivid visual hallucinations. • Fluctuation in cognition. • Motor signs of Parkinsonism and history of unexplained falls. • Visuo-spatial and frontal deficits are common. • Very sensitive to typical antipsychotic medication (it can cause death).

Types of dementia- less common causes • Frontotemporal dementia: insidious onset of language or personality changes. Disorientation is rare. • Huntington’s disease: hereditary progressive disease. Cognitive impairment, motor symptoms, and psychiatric disturbance. • Dementia in Parkinson’s disease: approx 30% of people with PD may develop a type of dementia very similar to DLB • Mixed dementias: mostly AD and Vascular dementia

Dementia Strategy Focus: • Early diagnosis • Better care in general hospitals & social care settings • Post diagnostic support • Reduction in inappropriate use of psychoactive medication • www.scotland.gov.uk

Mr & Mrs D • You meet Mrs D for the first time. She tells you she has just picked up her prescription for antidepressants. • Mr. D is with her because she can’t leave him alone. He is becoming increasingly confused and gets agitated if he can’t remember where he has put something. He has been worse over the last few days and is not sleeping at night. She says he has never been ill before, he has only ever had his blood pressure tablets. • What can you suggest to help Mr. & Mrs D?

Mr & Mrs G • Mr G is a 74 year old man who lives with his wife. He has a medical history of hypertension, angina and lower back pain. He has recently been started on Donepezil for Alzheimer’s Disease. • The couple have no formal support (e.g. home care) at home. • Mr G orders his own repeat prescriptions and collects them himself. He doesn’t run out of medicines, but sometimes forgets to take them.

Mr Gs Medication Elantan LA 25mg, 1 in the morning Simvastatin 10mg, 1 in the morning Co-codamol 1 or 2 as required Aspirin 75mg disp, 1 in the morning (before breakfast) Tildiem Retard 90, 1 twice daily (breakfast and lunch) Ranitidine 150mg, 1 at night Feldene gel four times daily Donepezil 5mg, 1 in the morning • Can you think of anything that could be done to help Mr. G stay as independent with his medication as possible for as long as possible? • As his dementia progresses what other resources are available to support him with his medication?

Importance of diagnosis • Many people in the early stages prefer to know. • Patients and carers need accurate and timely information in order to plan ahead. • Access to support and counselling. • Associated welfare benefits. • Legal advice and driving. • Availability of drug treatments.

History is the most important part of assessment and it must include: Onset and progression of symptoms. Medical history and medication. Psychiatric symptoms: focussing on memory, speech, and mood. Personal history including habits. Family history. Carer’s account. Assessment

Investigations are necessary to rule out reversible causes and confirm diagnosis. Treatable causes Hypothyroidism Vitamin B12 deficiency Depression Acute confusional state Neuro-imaging to confirm diagnosis CT, MRI, DAT Assessment and investigations

Delirium • Disturbance of consciousness and a change in cognition that can develop rapidly and, within a 24 hour period, can fluctuate widely. • Also called acute confusional state • Generally develops over hours or days • May be accompanied by signs of physical ill health • People with dementia are 5 times more likely to develop delirium than the rest of the population

Treatment for delirium • The most important approach to the management of delirium is the identification and treatment of the underlying cause: • Review drug treatment- medication may need to be changed or stopped • Correct biochemical abnormalities • If infection is suspected this should be treated with an antibiotic

Medication • Review medication to identify any drugs that may impair cognitive function on assessment and regularly afterwards • Assess co-morbidities including depression and psychosis

Medicines affecting cognition • Antihistamines • e.g promethazine, chlorphenamine, diphenhydramine (Nytol) • Antimuscarinics • antiparkinsonian e.g procyclidine • antispasmodic e.g hyoscine • for urinary incontinence e.g oxybutynin

Medicines affecting cognition • Antihypertensives • e.g propranolol (lipid soluble) • Antiparkinsonian agents • e.g levodopa, dopamine agonists • Antipsychotics • Anxiolytics and hypnotics • Diuretics • Oral hypoglycaemics • Steroids

Treatment of dementia • The next time you see Mr. & Mrs D, Mr. D has been told he will be started on donepezil. • What information should he and his carer be given? • What if he had been told he had vascular dementia and would not benefit from “memory enhancing” drugs. What advice and support could be offered to his wife who thinks “it is unfair that he can’t have the drugs unless he has Alzheimer's”?

Treatment of dementia • Non- pharmacological interventions Lisa will cover these in detail • Pharmacological Cognitive Enhancers Cholinesterase inhibitors Memantine Antipsychotics – place in therapy

Acetylcholinesterase inhibitors • Acetylcholine (ACh): neurotransmitter implicated in cognitive processes. • Degeneration of cholinergic neurones is a key feature of AD resulting in reduced levels of ACh in synapse. • ACh is metabolised by acetylcholinesterase (AChE). • AChE inhibitors increase the concentration of ACh by preventing its metabolism.

Acetylcholinesterase inhibitors • Donepezil, Galantamine, Rivastigmine • Side effects • Dose related cholinergic effects: Nausea, vomiting, diarrhoea, bradycardia, headache, dizziness, fatigue, muscle cramps, weight loss, sweating, disturbed sleep and nightmares

Acetylcholinesterase inhibitors • Cautions • Cardiac disease- sick sinus syndrome, bradycardia, conductivity defects • GI – susceptibility to ulcers • Asthma, COPD • Epilepsy • Drug interactions • Antimuscarinics • Muscle relaxants

After a few years – • Mrs D could no longer manage at home as Mr D had was up and down constantly at night and could become irritable and threatening towards her at times. He is now in a care home. • Mrs D is worried because donepezil has been stopped and changed to memantine. • Can you explain why donepezil has been stopped? • What are the indications for memantine? • Discuss potential side effects

Memantine • N-methyl D- aspartate (NMDA) receptor antagonist • Normalises abnormally high glutamate levels that may lead to neuronal dysfunction • Increasing evidence that malfunctioning of transmission at glutamatergic synapses contributes to symptoms and disease progression in neurodegenerative dementia

Memantine • Place in therapy • Severe AD or moderate AD where acetylcholinestarase inhibitors not tolerated. • NICE does not recommend combination therapy. • Side effects • Constipation, hypertension, headache, dizziness, drowsiness • Titrate dose • Patent expires 2014

Psychological delusions hallucinations elation/euphoria depression/dysphoria anxiety disinhibition Behavioural agitation/aggression irritability/ labile mood aberrant motor behaviour night-time behaviour appetite/eating changes apathy/indifference BPSD:Behavioural and Psychological Symptoms of Dementia

NICE Recommendations: Pharmacological interventions for BPSD • Pharmacological intervention should only be used if severe distress or when immediate risk of harm to patient/others • Prior to a pharmacological intervention, should consider a non-pharmacological option • Prescribers should follow an assessment and care-planning approach, including behavioural management • Antipsychotic drugs should not be prescribed in mild-to-moderate BPSD due to the possible increased risk of cerebrovascular adverse events & death

Treatment of BPSD • Mr D has been very distressed and agitated and has been hitting another patient. The plan is to prescribe risperidone. Mrs D is worried about this as she has heard about using drugs as a “chemical cosh”. • What should be considered before prescribing risperidone? • What are the potential risks / benefits • What are the alternatives? • How should the response be monitored? • What if MR. D had LBD or PDD?

Stress and distress • People with dementia who develop stress and distress should be assessed at an early opportunity to establish the likely factors that may generate, aggravate or improve such behaviour. • Common causes include depression, undetected pain or discomfort, side effects of medication

Pharmacological Interventions • Pain – always consider • Try regular paracetamol • Insomnia- sleep hygiene • temazepam, zopiclone (short term) • Anxiety/agitation- very common • Benzodiazepines (short term) – falls risk • Antidepressants – SSRIs, trazodone • Depression- very common • SSRIs, mirtazapine • Aggression and psychosis May require antipsychotics

Antipsychotics – MHRA advice • In elderly patients with dementia, antipsychotics are associated with a small increased risk of mortality and an increased risk of stroke or TIA. • Do not use to treat mild to moderate psychotic symptoms • Use only if benefits outweigh risks • Treatment should be reviewed regularly

MHRA advice • All SPCs require class wording in relation to a possible risk of CVA with all antipsychotics • ‘An approximately 3-fold increase of cerebrovascular adverse events has been seen in randomised placebo controlled trials in the dementia population with some atypical antipsychotics. The mechanism for this is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. …………(name of drug) should be used with caution in patients with risk factors for stroke.’

What is the risk of stroke? • Consider 1000 dementia patients taking antipsychotics for 6-12weeks • 972 will not have a stroke whether they take the drug or not • 11 would have stroke even if they didn’t take the drug • 17 may have a stroke because of the drug • So risk increases from 11 in 1000 to 28 in a 1000

What is the risk of death? • Consider 1000 dementia patients taking antipsychotics for 6-12weeks • 966 will not die whether they take the drug of not • 24 will die even if they don’t take the drug • 10 will die because they are taking the drug • So the risk increases from 24 in 1000 to 34 in a 1000

Typical Antipsychotics • Older drugs, more disabling side effect profile • Antimuscarinic symptoms • Cardiac effects • Extrapyramidal effects: parkinsonian symptoms, dystonia, akathisia tardive dyskinesia • Neuroleptic Malignant Syndrome • Haloperidol licensed for agitation and restlessness in older people NEVER in Lewy Body Dementia

Atypical Antipsychotics • Risperidone, olanzapine, quetiapine, aripiprazole, amisulpride, clozapine • Different side effect profiles include • Weight gain • Metabolic effects • Prolactin • Cardiac effects, especially postural hypotension • Hypersalivation • Sedation

Risperidone • Risperidone is licensed for the treatment of severe aggression in Alzheimer’s disease, which has not responded to other treatments • Duration of therapy is for short term use of up to 6 weeks • No other antipsychotics have a licence for the treatment of Alzheimer’s disease

Discontinuing Treatment • Mr. D had been very settled on risperidone but it is now being withdrawn. The dose has been halved over the last 2 months. He started continually asking Mrs. D who she is and denying she is his wife. She wonders why it is being stopped and asks “shouldn’t they be increasing the dose”? • Discuss • reasons to continue antipsychotics • Reasons to discontinue antipsychotics • How to withdraw the drugs safely

Discontinuing antipsychotics • In stable patients antipsychotic withdrawal should be considered (SIGN) • Withdraw gradually • Do not stop antipsychotics if there is a psychiatric diagnosis such as schizophrenia or psychotic depression - specialist advice

Stopping Treatment • Lack of clinical benefit. • Behavioural disturbances. • Obvious progression of the disease. • Side effects. • Reduce dose gradually to withdraw. • Deterioration may require therapy to be restarted

Potential alternative treatments for BPSD • Mood stabilisers: • Sodium Valproate (not recommended by SIGN) • Carbamazepine - increasing evidence • Citalopram • 2 promising RCT • 1v placebo, I v risperidone • Memantine • More studies in patients with clinically significant agitation required

End of life issues • Mr G’s condition has gradually deteriorated over the years, and for the last 6 weeks he has been cared for in a specialist dementia unit. He is now incontinent and bed bound. He is no longer able to eat and his fluid intake is poor. • What issues should be anticipated and planned for in the coming days or weeks?

End of Life issues • Constipation • avoid distressing treatments such as enemas if possible • Continence issues • Seek a cause and treat this wherever possible. Maintain the best possible hygiene and skin care to avoid infection • Swallowing problems • seek advice on appropriate alternate routes of administration • Infection • Scottish Antimicrobial Prescribing Group (SAPG) has published practice recommendations for antimicrobial use in frail elderly patients in Scotland.

End of Life Issues (cont.) • Pain • Treat empirically and assess response in terms of level of agitation, distress or observed signs of discomfort • Breathlessness • Small doses of opiates can be helpful either orally or by injection. • Family and carer support • Psychological social and spiritual needs • even in advanced dementia and the person will still get comfort from companionship. • Spiritual and religious beliefs

Dementia- What not to forget!