Pharmacological management of delirium Dr Paul Brown Consultant liaison psychiatrist for older adults 22nd June 2017

Three aspects of pharmacological management Treat the underlying cause Delirium risk reduction Active treatment of the delirium syndrome

Neuro-chemical factors Medical illness Predisposing factors Perfusion defects Neuro-chemical factors DELIRIUM Delirium DELIRIUM

Rationale for medication Common misconceptions exist! We are not aiming to ‘sedate’ the patient Some correlates in the delirium syndrome Dopamine and noradrenaline hyperactivity Altered serotonin activity Cholinergic deficiency Melatonin abnormalities Inflammation

Antipsychotics: Typicals Atypicals Delirium Benzodiazepines Cholinesterase inhibitors Sleep-wake cycle regulators Low dose antidepressants

Delirium risk reduction NICE 2010 NICE guidance update 2012 Cochrane Review 2016 Multiple agents of interest Acetylcholinesterase inhibitors Typical antipsychotics Atypical antipsychotics Melatonin Gabapentin

Based on the limited evidence Outcomes of interest Reduction in delirium incidence Duration Severity Hospital stay Based on the limited evidence No recommendations for routine practice Non-pharmacological approaches critical

Melatonin of considerable interest Melatonin abnormalities linked to delirium Some evidence of benefit in dementia 2x RCT’s, multiple case reports Inconsistent results Generally well tolerated in studies Has a license for primary insomnia Has anti-inflammatory properties

Active treatment Outcomes of interest NICE guidance 2010 Achieve complete response Duration Severity NICE guidance 2010 Only three studies included to assess efficacy Recommends a trial of haloperidol or olanzapine Subject to criteria Short-term treatment

Cochrane Review 2009 of benzodiazepines Only one study met inclusion criteria RCT evaluating lorazepam Nice guideline update 2012 Single-blinded RCT: emerging evidence of comparable efficacy of olanzapine/risperidone with haloperidol Doube-blinded RCT evaluating rivastigmine

Emerging, cautious evidence of equal efficacy between haloperidol and: Risperidone Olanzapine Aripiprazole Quetiapine Suggest matching drug feasibility/tolerability to patient Normal practice remains to follow NICE guidelines where possible

Prescribing in cardiac disease Many psychotropic drugs affect the heart QTc interval very important Olanzapine low effect Risperidone low effect Aripiprazole neglible effect Haemodynamic factors Obtain ECG pre-prescription

Prescribing in metabolic disease Impaired glucose tolerance and diabetes Metabolic syndrome Assess cardio-metabolic risk factors Monitor on treatment Olanzapine, quetiapine problematic Better choices Aripiprazole, haloperidol

Prescribing in Parkinson’s disease (PD) and Lewy Body dementia (LBD Dopamine antagonism Can exacerbate Sx Review PD medication Review AcH medication Better choices Benzodiazepines Quetiapine Olanzapine Aripiprazole Please avoid haloperidol!

Key points when prescribing Start slow, go slow ‘think frailty’ Avoid the common pitfalls Monitor physical health closely Daily check for culprit medications (deliriogenic drugs) Regular prescription vs PRN Avoid poly-pharmacy Off-label prescribing Interactions Consistent delivery Tablets/capsules, liquid, oro-dispersable, IM Adults with Incapacity Act/Mental Health Act Covert prescription Daily medication review

Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study Hatta et al, International Journal of Geriatric Psychiatry 2013 Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials Kishi et al, Journal of Neurology, Neurosurgery and Psychiatry, 2016

Conclusion Appropriate use in the right patient can confer benefit Avoid benzodiazepines in most cases of delirium More high quality RCT’s are required in this (until recently) neglected field A rational, evidence based approach will prevent allegations of ‘chemical cosh’!