What is delirium? DSM IV criteria St Francis Hospice Dr Hilary Kinsler Disturbance of consciousness reduced clarity of awareness of the environment Change in cognition memory deficit, disorientation, language disturbance, perceptual disturbance occurs that is not better accounted for by a pre-existing, established, or evolving dementia. The disturbance develops over a short period and tends to fluctuate during the course of the day. Evidence from the history, physical examination, or laboratory findings is present that indicates the disturbance is caused by a direct physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more than one cause. Delirium vs Dementia Delirium Dementia Onset Acute Insidious Duration Transient Chronic Course Fluctuating Progressive Attention Reduced Intact initially Consciousness Altered Normal Hallucinations Common Less common Delirium may be superimposed on dementia How common is it? Delirium is common in acute hospitals e.g. - 1-2 % In community 22% in general medicine in patients 28% acute orthopaedics 40% Post op 50% Geriatric medicine in patients 80% medical ICU 88% palliative care How is it prevented? The environment: Hearing aids Spectacles Orientation aids Lighting Encourage food and fluid intake Encourage mobility Maintain sleep pattern Involve relatives and carers Avoid: Constipation Catheters Restraint Sedation Bed or Ward moves Arguing with the patient Anticholinergics 1
Anticholinergic drugs. Full List of Anticholinergic medication Type of drug Antihistamine Antispasmodic Tricyclic antidepressant Benzodiazepine Analgesic Antiarrhythmic Diuretic Antiparkinsonian Bladder stabiliser Brochodilator Example Hydroxyzine, diphenhydramine Alverine, hyoscyamine Amitriptyline Lorazepam Codeine Digoxin Furosemide Orphenadrine, Procyclidine, benzatropine (more often used in US than UK) Oxybutynin Theophylline Aging brain Care Anticholinergic Burden Scale Evidence Base for Haloperidol in Delirium Author Type Year Outcome Page Boogaard Kalisvaart Kaneko Randomised double Blind ICU 141 patients Before after evaluation ICU RDB prophylactic HPL 1.5mg before hip surgery Randomised Comparative 78 patients 5mg 2013 Negative 2013 Probably +ve 2005 Incidence -ve Severity -+ve Duration +ve 1999 Positive Wang RDB ICU 2012 Positive Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care A Randomized Clinical Trial Meera R. Agar, PhD Jan 2017 Question What are the benefits of risperidone or haloperidol in reducing distressing symptoms of delirium in patients receiving palliative care? Findings In this randomized clinical trial of 247 participants receiving palliative care, distressing behavioral, communication, and perceptual symptoms of delirium were significantly greater in those treated with antipsychotics (risperidone or haloperidol) than in those receiving placebo. Meaning Antipsychotic drugs are not useful to reduce symptoms of delirium associated with distress in patients receiving palliative care. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials Taro Kishi Sept 2015 Our results suggested that second generation Antipsychotics have a benefit for the treatment of delirium with regard to efficacy and safety compared with haloperidol. However, further study using larger samples is required. If medication is really, really needed Regular risperidone (liquid) up to 0.5mg nocte and 0.5mg PRN (0.25mg if very frail, higher does if less frail) If refuse oral and has to be IM lorazapam 1mg (or haloperidol 1mg) Benzodiazepines make delirium worse. Mirtazapine 15mg nocte can help, comes as orodispersible. More helpful in hyperactive delirium. 2
Antipsychotics When are antipsychotic Medications Used? Not just for psychosis! Depression, anxiety, bipolar affective disorder, behavioural problems in dementia, eating disorders, insomnia etc etc. Reduction of antipsychotics in psychotic illnesses Must be done gradually because of risk of relapse and risk of tardive dyskinesia Procyclidine makes tardive dyskinesia worse and increases risk of delirium. Tardive Dyskinesia Abnormal movements which develop either when people are on antipsychotics or a few weeks after they are stopped or dose reduced. Treatment is very difficult. Procyclidine makes it worse but helps parkinsonian side effects of antipsychotics. Potent anticholinergic. Withdrawal symptoms of antipsychotics Agitation Insomnia Rebound psychosis Tardive dyskinesia Anticholinergic rebound: nausea, malaise, diaphoresis, vomiting, and/or insomnia Dementia Medications 3
Percentage of patients showing improvement at week 24/28 (LOCF) LS mean change from baseline item score at Week 24 (LOCF) How are they taken? Tablet Capsule Orodispersible tablet Donepezil Galantamine * * Oral solution Transdermal patch Rivastigmine * * Memantine *Twice daily dosing required; all other preparations are administered once daily Donepezil and reduced worsening Pooled data from 3 large trials of donepezil in Alzheimer s disease Definition of clinical worsening incorporated: Cognition Global outcome Function Patients on placebo more likely to show clinical worsening than patients on donepezil -2.0-1.5-1.0-0.5 0.0 0.5 1.0 NPI 12-item Total: Moderate to Severe AD NPI Individual Item Analysis Donepezil Placebo P = 0.0166 P = 0.0128 P = 0.0018 Clinical improvement Clinical decline How safe are cholinesterase inhibitors? Most common side effects Nausea and vomiting & diarrhoea Cramps Abdominal pain & anorexia Vivid dreams Slow Heart rate Peptic ulcer and gastric bleeding urinary retention and frequency Stopping can be done without reducing dose but risk that cognition crashes. Gauthier S et al. Int J Psychogeriatr. 2002;14:389-404. NPI domains: improvement in baseline symptoms Pooled data from six studies (MMSE <20), % of patients showing improvement, NPI single items (LOCF) 75 70 65 60 55 50 45 40 * Delusions Hallucinations Agitation/aggression Depression/dysphoria Anxiety Elation/euphoria Apathy/indifference Memantine * Disinhibition Irritability/lability Aberrant motor behaviour Placebo Night-time behaviour Appetite/eating change *p<0.05 Gauthier et al. Int J Geriatr Psych 2007 Gauthier et al. Int J Geriatr Psych 2008;23:537-45 * * How safe is memantine? No absolute contra-indications BNF advises caution in presence of seizures However no real data one way or the other May need reduced dose in CKD Can be discontinued without reduction but collateral always a good idea. Generally well tolerated. The most common listed side effects are: Constipation Dizziness Headache Hypertension Somnolence 4
What I do No point in discontinuing safe medication which reduces agitation unless you have too. Reduce dose in renal failure & stop if severe. Sometimes stopped if seizures but can get seizures in dementia anyway so need to check response. Can be stopped gradually or without titrating but if it has been helping behaviour it can be a disaster to stop suddenly so best to reduce slowly. Response to memantine is very variable so check initial response. In LBD or Dementia in PD. Discontinuing rivastigmine in PD or LBD can cause severe and distressing hallucinations even in someone with very poor cognition. Major Depression Is Associated with Chronic Medical Illness 30 25 6% 25% Antidepressants Prevalence of Major Depression (%) 20 15 10 5 2% 4% 5% 10% 6% 14% 0 Community Primary Care Clinic Medical Inpatient Setting Katon W, Schulberg H. Gen Hosp Psychiatry. 1992;14:237-247. Rosen J, Mulsant BH, Pollock BG. Nursing Home Med. 1997;5:156-165. Nursing Home Prevalence of Depression in Palliative Care Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst. 2004;32:57 71. 38% Antidepressants for the treatment of depression in palliative care: systematic review and metaanalysis Rayner L, Price A, Evans A, Valsraj K, Hotopf M, Higginson IJ Antidepressants for Depression Choice History Risks Biological Symptoms Triad of Early morning wakening, Diurnal mood variation & anhedonia 5
Type SSRI Selective serotonin reuptake inhibitor SNRI Selective noradrenaline reuptake inhibitors NaSSA - Noradrenergic and specific serotonergic antidepressants SARI Serotonin antagonist and reuptake inhibitor TCA tricyclic antidepressants Examples Citalopram Escitalopram Paroxetine Fluoxetine Sertraline Fluvoxamine Duloxetine Venlafaxine Desvenlafaxine Mirtazepine Trazodone Amitriptyline Dosulepin Doxepin Imipramine Mirtazapine Helps sleep and increases appetite Not anticholinergic Well tolerated Over sedation and postural hypotension are main side effects Comes as orodispersible and as a liquid Withdrawal symptoms 53% have withdrawal symptoms. anxiety (70%) dizziness (61%) vivid dreams (51%) electric shocks / head zaps (48%) stomach upsets (33%) flu like symptoms (32%) depression (7%) headaches (3%) suicidal thoughts (2%) insomnia (2%). Do antidepressants work in dementia? Depression affects up to 43% of patients with dementia Likely to be offered antidepressant medication Evidence that antidepressants work for depression in dementia is patchy HTA-SADD study (Banerjee et al, 2011 Lancet) No consistent benefits on symptoms of depression - Sertraline no effect - Mirtazapine reduced carer burden Lack of efficacy of antidepressants suggests different pathogenic mechanisms for depression in AD Anticholinergic Medications Treating bladder symptoms in dementia 1st line review bladder anticholinergic, use non-drug measures 2nd line: trospium (non-selective but poor penetration through BBB, P-gp substrate and no CYP450 function, low risk of interactions) darifenacin (selective and P-gp substrate). 3rd line: solifenacin (somewhat selective but readily penetrates BBB, not P-gp substrate and has potential to cause cognitive impairment). Data for fesoterodine is still lacking but it is non-selective, has high central anticholinergic activity but theoretically has low ability to cross BBB. Or use Mirabegron 6
Antiemetics For people with dementia cyclizine,metoclopramide, and prochlorperazine should not be first line antiemetics. Hyoscine hydrobromide (Kwells) should be avoided Domperidone is a good first line choice and 5- HT3 antagonists are also safe to use Benzodiazepines What I do with benzos Extremely, extremely cautious if on long term treatment. Incredibly slow reductions if really essential. Can get psychotic symptoms and symptoms suggestive of delirium. I have had some disasters! Withdrawal symptoms Anxiety and Perceptual distortions Anxiety, irritability, excitability, panic attacks Sleep disturbance Visual disturbance, sweating Altered mood, paranoid thoughts Hypersensitivity (light, sound, touch, taste, smell) Abnormal body sensations Depersonalisation, derealisation Depression Physical symptoms Tremor, muscle spasms, hyperventilation Anorexia, weight loss Major events Generalised seizures Precipitation of delirium or psychotic symptoms Lithium Continue as long as possible! Safer opiates in dementia Buprenorphine- fewer side effects and patch makes administration easier Oxycodone- short half-life, few drug-drug interactions, predictable dose-response 7
Antihistamines Antiepileptics Avoid first generation drugs - chlorpheniramine, clemastine, promethazine, cyclizine, cyproheptadine, hydroxyzine Second generation drugs are safe- loratadine, fexofenadine, cetirizine BNF defines which are sedative and nonsedative Topiramate and Levetiracetam Agitation, anxiety, nervousness, depression, emotional lability, irritability, hostility, aggressive behaviour and psychosis. Steroids Prednisolone. Poor sleep, increased appetite, elated mood, irritability, visual hallucinations, psychosis. Depression, muscle pain, lethargy on withdrawal. 8