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Dementia Stephen Bleakley, Deputy Chief Pharmacist Southern Health NHS Foundation Trust October 2013 Director: The College of Mental Health Pharmacy Outline Facts and figures Symptoms Types of dementia and pathology Diagnosis Management Behavioural & psychological symptoms of dementia (BPSD) What is dementia? A progressive degenerative neurological disease • Affects 800,000Dementia people in the UK – 5% of those aged over 65 – 20% over 80s • Figure expected to double over the next 30 yrs • Predominant features are – cognitive decline – loss of functional ability • Accompanying behavioural symptoms in about 90% of patients Cognition A group of mental processes that include: • • • • • Attention and memory Learning and retaining new information Reasoning, problem solving Decision making Understanding and producing language i.e being able to receive information, comprehend it, store it, retrieve it and use it Functional ability Able to perform Activities of Daily Living (ADL) • Basic ADL skills: • Personal hygiene, grooming • Dressing/undressing, self-feeding • Functional transfers (on/off bed or toilet) • Bowel and bladder management • To be able to live independently (higher level): • Housework • Taking medication • Shopping/ groceries • Managing money Risk factors for dementia Age Gender (women > men) Genetic About 1 in 4 cases are familial 1st degree relatives have 2.5 fold increased risk Downs syndrome High BP, high cholesterol, smoking, alcohol Other: Low IQ/ education level, head injury, toxins e.g. aluminium (?) Types of dementia Alzheimer’s disease Vascular Dementia Dementia with Lewy Bodies (DLB) Mixed dementia Others Alzheimer’s disease Most common type (60%) Insidious onset, gradual deterioration First sign is failing memory Cognition, language, behaviour and ADL all affected Women > men Profound cholinergic loss Cholinergic Hypothesis Degeneration of cholinergic neurones A reduction in levels of acetylcholine released at the cholinergic synapse Cognitive deterioration results Vascular Dementia Caused by ischaemic damage to the brain Usually follows a stroke or multi-infarct Abrupt onset, stepwise deterioration Depression can be common No licensed treatment Dementia with Lewy Bodies (DLB) Presence of abnormal protein deposits inside nerve cells Clinical Features Dementia Parkinsonism (rigidity, tremor) Visual hallucinations Fluctuation in severity Extreme sensitivity to antipsychotic drugs No licensed treatment Diagnosis • Exclude physical causes • Cognitive Assessments eg Mini Mental State Examination (Psychiatrist/ psychologist) • ADL functioning (Occupational Therapist) • Involve relatives and carers Physical Causes • Confusion, delirium, cognitive impairment can also be caused by: – Hyponatraemia – Hypoglycaemia – Hypothyroidism – Alcohol related disease – Low vitamin B12 and folate levels – Urinary Tract or chest infections – Medicines eg antipsychotics, anticholinergics Mini Mental State Examination What is the year, season, date? Where are we? country, city, floor? Name 3 objects: table, apple, penny Serial of 7s Spell “WORLD” backwards “No ifs ands or buts” Follow a command: Take a paper in your right hand, fold it in half & put it on the floor Read and obey: (close your eyes) Copy this diagram Acetylcholinesterase Inhibitors Donepezil (Aricept) Mech. of Inhibits action AChE Rivastigmine (Exelon) Galantamine (Reminyl) Inhibits Inhibits AChE and AChE and BuChE nicotinic agonist AChE = Acetylcholinesterase BuChE = Butyrylcholinesterase Acetylcholinesterase Inhibitors They all essentially work in the same way They inhibit the enzyme(s) which is responsible for the breakdown of Acetylcholine Leading to increase in Acetylcholine in the brain They are not a cure but stabilise memory for a few months/ years They don’t work for everyone (NNT 4-12) NICE recommend them for mild to moderate Alzheimer’s Disease only (not in vascular or LBD although sometimes used off-license) Comparisons of AChEIs Drug Advantages Disadvantages Donepezil Once daily dose Not affected by food Interactions Rivastigmine Patch Twice Galantamine Liquid and liquid available Interactions with other drugs unlikely occur No liquid can daily dose for capsules. Reduced absorption if taken with food available Interactions can occur Modified release once daily capsules available Food slows down absorption of drug Cholinergic Side Effects GI disturbance nausea, vomiting, diarrhoea (take with/after food) Weight Loss Headache / Dizziness Fatigue Muscle Cramps Sweating Disturbed sleep and nightmares Bradycardia (caution in sick sinus syndrome) Interactions with AChEIs Drug Metabolism Levels increased by Donepezil (Aricept®) Substrate at Ketoconazole CYP 3A4 and Itraconazole 2D6 Erythromycin Quinidine Fluoxetine Rivastigmine (Exelon) Non-hepatic metabolism Galantamine (Reminyl) Substrate at Ketoconazole CYP 3A4 and Ritonavir 2D6 Erythromycin Quinidine Fluoxetine Paroxetine Amitriptyline Levels decreased by PD interactions Rifampicin Phenytoin CBZ Alcohol Anticholinergic Cholinergic agonist Muscle relaxants (succinylcholine) Beta blockers PK interactions unlikely (May inhibit metabolism of substances mediated by BuChE eg cocaine, heroin) None reported The Maudsley Prescribing Guidelines – 11th Edition Anticholinergic Cholinergic agonist Muscle relaxants Anticholinergic Cholinergic agonist Muscle relaxants Beta/ Ca-channel blockers, digoxin, amiodarone AChEI + Anticholinergics • Avoid combination where possible. • Inefficient use of AChEIs- not cost-effective • Anticholinergics can also cause delirium, confusion, disorientation etc.. • If a bladder anticholinergic drug is required then best to chose: • a more (bladder) selective drug eg Darifenacin (less impairment of cognitive function) or • one with reduced penetration through the BBB eg Trospium (reduced CNS effects) Australian Prescriber | VO L UME 2 9 | N UMB E R 1 | F E B R UA RY 2 0 0 6 Memantine (Ebixa®) NMDA (N-methyl-D-aspartate) antagonist Glutamate binds to NMDA receptors allowing calcium into the brain nerve cell- cell degeneration Memantine prevents this destruction by blocking the NMDA receptor site For Moderate to Severe Alzheimer’s disease 5mg daily increased by 5mg weekly to 20mg daily S/Es: constipation, headache, dizziness, hypertension, drowsiness Drug interactions of Memantine Drug Metabolism Levels increased by Levels decreased by Pharmaco-dynamic interactions Memantin e Primarily non-hepatic Cimetidine Ranitidine Procainamide Quinidine Quinine Nicotine None known Effects of L-dopa, dopaminergic agonists and anticholinergics may be enhanced Renally eliminated Carbonic anhydrase inhibitors, sodium bicarbonate Isolated cases of INR increases with warfarin Effects of barbiturates and neuroleptics may be reduced Avoid combination with amantadine, ketamine, dextromethorphan Dose adjustments for antispasmodics, dantrolene or baclofen Taylor D, Paton C, Kapur S. Maudsley Prescribing Guidelines in Psychiatry - 11th Edition. Oxford, UK: Wiley-Blackwell; 2012. Stopping Treatment Lack of clinical benefit difficult to assess Worsening of condition Side effects Reduce dose gradually to withdrawal NICE Guidance (Updated March 2011) • AChEIs recommended in mild-moderate AD • Memantine recommended in: – Moderate AD in pts intolerant to AChEIs – Severe AD (MMSE < 10) • When assessing severity, do not rely solely on cognition scores – Consider linguistic difficulties, level of education, cultural background – Hearing, vision, learning disability, communication problems • Except in clinical trials, do not use: – AChEIs or memantine in vascular dementia – AChEIs in Mild Cognitive Impairment (MCI) Quiz- Dementia • Name the 3 most common types of Dementia. • Which type may occur after a stroke? • In which type must you always avoid antipsychotics? • How does the main class of medication for AD work? • What are some of the side effects of AChEIs? • When should you use Memantine? Behavioural & Psychological Symptoms of Dementia (BPSD) • Anxiety • Agitation & aggression • Insomnia • Hallucinations, delusions • Depression • Wandering, disinhibition • Vocalisations Triggering factors • BPSD may be caused by: –Pain –Constipation –Infections (eg. UTI, chest infection) • Eliminate these potential causes first • Symptoms may resolve BPSD Leads to: – Considerable carer burden – Care home admissions – Hospital admissions – Increased cost of care • Causes still unknown • Various neurotransmitters implicated – Acetylcholine, dopamine, serotonin Non-pharmacological Management Psychological therapies Aromatherapy (evidence for lavender & Melissa balm) Snoezelen rooms (specially designed rooms with soothing and stimulating environment) Pet therapy Music therapy Massage therapy Reflexology Homeopathy The best non-drug approaches Individualised Engaging care activities Compassion and empathy Chemical Cosh’ for dementia kills 1,800 Britons a year 1,800 a year die from dementia ‘cosh’ pills Adverse effects of antipsychotics in dementia Stroke risk-3-fold increase risk of stroke Mortality rate 1.6 to 1.7 times higher Hastening of cognitive decline DLB extreme sensitivity to antipsychotics EPSEs Sedation, increased agitation Metabolic side effects Warnings with ALL typical and atypical antipsychotic drugs ONLY Risperidone licenced for BPSD: -“Up to 6 weeks’ treatment of persistent aggression in patients with moderate to severe Alzheimer’s dementia who have not responded to non-pharmacological approaches and where there is a risk of harm to themselves or others” When prescribing antipsychotics in Dementia • • • • • • • • • Exclude physical illness eg pain, infection Target the symptom requiring treatment Consider non-pharmacological methods first Carry out risk/benefit analysis Discuss options and risks to patient and relatives/carers Maintain lowest possible dose for shortest period Review appropriateness of treatment (every 3 months) Monitor for side effects Document clearly treatment choices and discussions with patient, family or carers Other Pharmacological Management • Benzodiazepines • Antidepressants (SSRIs, trazodone) • Mood stabilisers (carbamazepine,valproate) • Acetylcholinesterase inhibitors/ Memantine • Paracetamol • Antipsychotics How can pharmacists help? Role of the pharmacist Help identify those in need of referral To provide up to date information on efficacy and safety of drugs to patients, carers & prescribers Help to ensure national guidance is followed Encourage regular review / audit of medication in BPSD Efficacy benefits Adverse effects THUS: Improve clinical outcomes & quality of life in pts and decrease burden to family and carers Web resources • www.choiceandmedication.org/southernhealth • www.southernhealth.nhs.uk – Shared care guidelines on AChEIs and memantine • • • • http://www.alzheimers.org.uk/ http://www.dementiauk.org/ http://www.marc.soton.ac.uk/ http://www.dendron.nihr.ac.uk/ THANK YOU [email protected] www.southernhealth.nhs.uk www.cmhp.org.uk References • Oxford Textbook of Psychiatry- Part 4- Dementias • Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines 11th Ed • Bishara D. The Pharmacological Management of Alzheimer’s Disease. Progress in Neurology and Psychiatry. 2010; 14: 16-22 • Mini Mental State Examination -adapted from Folstein et al • NICE Clinical guideline 42. Dementia. Revised March 2011