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. Lorazepam IM (again)
2. Haloperidol + Promethazine IM (again)
3. …“arrange an urgent team meeting” !
• “Consider antipsychotics 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? delirium? Other medicines? Epilepsy?
• Cognitive: Communication difficulties? Learning disability? Autism? Dementia?
• Substance misuse? Alcohol?
• Withdrawal symptoms?
• Psychological or emotional factors?
• Most restraints occur on acute medical wards (not in A&E)
• MH problems present in 5% of all A&E attendances
• 30% general hospital inpatients (45% in older people)
• Most commonly: depression, delerium, dementia, 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, Excretion
Pharmacodynamics
• Onset of Action • Oral: Roughly 30mins, may be longer (Check if swallowed!) • IM: Quicker onset of action than orals, approx 15-30mins
Medicine Route Onset of effect Time to
peak effect Duration of
effect Reversing
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 mins)
2-3 hours 12 hours (4-6hrs)
None
IM 30-60 mins 1-2 hours 10 hours (2-8hrs)
Risperidone Oral 30-60 mins 1-2 hours 12-24 hours None
Medicine Route Onset of effect Time to
peak effect Duration of
effect Reversing
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 mins)
2-3 hours 12 hours (4-6hrs)
None
IM 30-60 mins 1-2 hours 10 hours (2-8hrs)
Risperidone Oral 30-60 mins 1-2 hours 12-24 hours None
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?
Lorazepam (1971)
“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: “Sedation & 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 aggression & violence
• Practical – administration
• Restraint injuries to staff
• Needle stick injuries / injection 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 2009; 23(6):477-492.
2. Trollor JN et al. BJPsych 2012.
3. Manu P et al. J Clin Psychiatry 2011; 72(2): 936-941.
• Accumulation (over-sedation, respiratory depression)
• Tolerance, addiction
• Behavioural patterns
Risks with benzodiazepines
Risks with IM promethazine
• Slower onset of action 1-2 hours
What if a dose of RT doesn’t work?
• Pharmacokinetics
• Consider length of needle for IMs if patient is obese
• Review
– Diagnosis
– Presentation/goal
– Current prescriptions
– Involve psych liaison team
• Don’t just keep doing the same….
Urine Drugs Screens Remember these
don’t test for
EVERTHING
- not “illegal highs”
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 antipsychotic in
the absence of a psych diagnosis
Summary
• LOTs of guidance around use of medicines in the management of disturbed & aggressive or violent behaviour
• “Chemical restraint” 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”
• Active metabolites including N-desmethyldiazepam with a half-life of 30 - 100 hours
• Terminal elimination phase 1-2 days
• Licensed for anxiety & insomnia
• BNF 4.2.1 – anxiolytics (T2/3)
• Tabs & liquid
• Max. 30mg/day
Clonazepam • “Long acting” • Active metabolites • Terminal elimination half-life of 20
- 60 hours (mean 30 hrs) • Greater inter-individual variation
in response • Unlicensed indication • BNF 4.8.1 – antiepileptic (T2/3) • Tabs & liquid (liq = £++) • 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