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Positive & Safe –

Medicines as Restrictive interventions?

Caroline Parker Consultant Mental Health Pharmacist Overview

• Medicines are the most widely used health intervention in the UK

Consider what national guidelines say about medicines in the management of violent and aggressive behaviour in health settings

the medicines recommended to calm aggressive patients, and consider when these are best used, and their risks

Consider if/how medicines are used as restrictive interventions 1 National Guidance Identify patterns to predict behaviour

NICE Guidelines – Definitions & Concepts • “Rapid Tranquillisation” = parenteral = IM • “PRN” • Review, review, review 1. IM (again) 2. Haloperidol + IM (again) 3. …“arrange an urgent team meeting” !

• “Consider to manage behaviour that challenges only if”: – Psychological or other interventions don’t help – Treatment of co-existing problems hasn’t helped – Risk to pt or others is “severe” • Only offer antipsychotics in combinations with psychological or other interventions 2. Recap - Medicines the medicines recommended to calm aggressive patients, and consider when these are best used, and their risks. Causes? Why do people become aggressive & violent?

• Physical – pain? ? Other • Most restraints occur on acute medicines? Epilepsy? medical wards (not in A&E) • Cognitive: Communication • MH problems present in 5% of difficulties? Learning disability? all A&E attendances Autism? ? • 30% general hospital inpatients • Substance misuse? ? (45% in older people) • Withdrawal symptoms? • Most commonly: depression, • Psychological or emotional delerium, dementia, factors? adjustment reactions and alcohol related

Management options should be as tailored as the reasons are varied. Drug Treatments - principles

What’s the goal? – safety of everyone, calm patient (not asleep) • Identify target symptoms • Underlying (ongoing) illness is 2ndry Only use drugs when risks of doing so > risks of not doing so

Pharmacokinetics Absorption, Distribution, Metabolism,

• Onset of Action • Oral: Roughly 30mins, may be longer (Check if swallowed!) • IM: Quicker onset of action than orals, approx 15-30mins Time to Duration of Reversing Medicine Route Onset of effect peak effect effect agent IM 30-45 mins 1-3 hours 18-24 hours None Diazepam IV 5-10 seconds <1 min 12-24 hours Flumazenil Haloperidol oral 1-2 hours 2-6 hours 18-24 hours None IM 15-30 mins 20 mins Lorazepam oral 20-30 mins 2 hours 6-8 hours Flumazenil IM 15-30 mins 60-90 mins Oral ≈ 2 hours 5-8 hours 24 hours None IM 15-30 mins 15-45 mins Promethazine Oral ≈ 2 hours (15-30 2-3 hours 12 hours (4- None mins) 6hrs) IM 30-60 mins 1-2 hours 10 hours (2- 8hrs) Oral 30-60 mins 1-2 hours 12-24 hours None Time to Duration of Reversing Medicine Route Onset of effect peak effect effect agent Aripiprazole IM 30-45 mins 1-3 hours 18-24 hours None Diazepam IV 5-10 seconds <1 min 12-24 hours Flumazenil Haloperidol oral 1-2 hours 2-6 hours 18-24 hours None IM 15-30 mins 20 mins Lorazepam oral 20-30 mins 2 hours 6-8 hours Flumazenil IM 15-30 mins 60-90 mins Olanzapine Oral ≈ 2 hours 5-8 hours 24 hours None IM 15-30 mins 15-45 mins Promethazine Oral ≈ 2 hours (15-30 2-3 hours 12 hours (4- None mins) 6hrs) IM 30-60 mins 1-2 hours 10 hours (2- 8hrs) Risperidone Oral 30-60 mins 1-2 hours 12-24 hours None Lorazepam (1971)  Short acting benzodiazepine, no active metabolite  low risk of accumulation  Bio-equivalent (no first pass hepatic effect): po = IM  Onset of action IM: 15-30mins (po: 20-30mins)  Peak IM: 60-90 minutes (po: 2 hours)  t½ : 12-16 hours , duration effect: 6-8 hours  National shortages since 2005  buying unlicensed version from abroad - legal implications  Qu. Maximum dose IM? “Acute Anxiety Adults: 0.025-0.03mg/kg (1.75-2.1mg for an average 70kg man). Repeat 6 hourly” Haloperidol (1959)  10mg po = 6mg IM  No longer licensed for IV use  Onset of action IM: 15-30mins, (po: 1-2 hours)  Peak IM: 20 minutes (po: peak 2-6 hours)  t½ 21 hours, duration effect 18-24 hours  BNF maximums now 20mg/d po, 12mg/d IM  Extrapyramidal side effects – prescribe procyclidine  ECG monitoring requirements  SPC: “Baseline ECG is recommended prior to treatment in all patients, especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination…… discontinue if the QTc exceeds 500ms.”  Very rare reports of QT prolongation +/or ventricular arrhythmia  Maybe more frequent with high doses & in predisposed patients  Concomitant use of other drugs that ↑QT interval may ↑risk Promethazine IM (Phenergan)

Licensed indications: “ & treatment of insomnia in adults” • TREC trials x4, with haloperidol • An option when lorazepam can’t be used: – e.g. patient is tolerant / addicted – Can’t tolerate them e.g. severe respiratory disease • Slower onset of action 1-2 hours – (po, peak 2-3 hours) • t½: 7-15 hours • Dose: 25-50mg, max 100mgs Risks with medicines for & violence

• Practical – administration • Restraint injuries to staff • Needle stick injuries / errors • ADRs and inability to monitor pts physical state

Risks with all Antipsychotics

• Neuroleptic Malignant Syndrome (NMS) with all antipsychotics 1,2 – Potentially fatal, completely unpredictable • Cardiovascular – arrhythmias – more likely with higher doses, consider total daily dose • Seizures • Extrapyramidal side effects – (especially with haloperidol) • Sudden cardiac death – association with antipsychotics may be over estimated3

1. Trollor JN et al. CNS Drugs 3. Manu P et al. J Clin Psychiatry 2009; 23(6):477-492. 2011; 72(2): 936-941. 2. Trollor JN et al. BJPsych 2012. Risks with benzodiazepines • Accumulation (over-sedation, respiratory depression) • Tolerance, addiction • Behavioural patterns

Risks with IM promethazine • Slower onset of action 1-2 hours What if a dose of RT doesn’t work?

Urine Drugs Screens • Remember these • Consider length of needle for IMs don’t test for if patient is obese EVERTHING • Review - not “illegal highs” – Diagnosis – Presentation/goal – Current prescriptions – Involve psych liaison team • Don’t just keep doing the same…. Patients Perspective?

What do consumers say they want and need during a Psychiatric Emergency ? Allen et al. J Psych Prac 2003

Patients Perspective?

• Patients want to be listened to, spoken to, treated with respect and given oral medication of their choice

• Rated distraction highly, such as art or music and access to staff they knew and spiritual counsellors

• Preferred space to be able to walk about and access to food & drink

• Although over 50% wanted medication they complained of forced administration and unwanted side effects

• Benzodiazepines were preferred option, haloperidol the least preferred option

• Supported increased use of advance directives 3. Medicines as restrictive interventions

Polypharmacy

• Prof Sube Banerjee’s “A time for action” (2009)

• Kings fund – “problematic” polypharmacy

• Dementia NICE

• POMH LD data – 20% of adults with a severe LD are prescribed an in the absence of a psych diagnosis

Summary

• LOTs of guidance around use of medicines in the management of disturbed & aggressive or violent behaviour

• “” is far more than just RT

• Evidence of over-use (prescribing & administration) of medicines in a range of settings

• Challenge is implementing other approaches Any Questions? Benzodiazepines

Diazepam • “Long acting” • “Long acting” • Active metabolites including N- • Active metabolites desmethyldiazepam with a half-life • Terminal elimination half-life of 20 of 30 - 100 hours - 60 hours (mean 30 hrs) • • Greater inter-individual variation Terminal elimination phase 1-2 days in response • Licensed for anxiety & insomnia • Unlicensed indication • BNF 4.2.1 – anxiolytics (T2/3) • BNF 4.8.1 – antiepileptic (T2/3) • Tabs & liquid • Tabs & liquid (liq = £++) • Max. 30mg/day • Max. 8mg/day

Equivalent doses – no consensus: Approximately Diazepam 5mg = Clonazepam 0.5mg Ranges quoted: 0.5 – 1mg, 0.5mg (0.25 -4mg), 0.25mg RT - Benzos or Antipsychotics?

Benzos ≈ Antipsychotics Benzos+Antipsychotics ≈ Benzos ≈ Antipsychotics Benzos+Haloperidol < Olanzapine Midazolam+Haloperidol > Olanzapine Only parenteral benzodiazepines No head-to-head benzo studies