Drug treatment of Acute Behavioural Disturbance in Adult (18-65 years)

Intramuscular Drug Treatment of Acute Behavioural Disturbance Adults (18-65 years old):

Note:

IM Promethazine 50mg can be used if Lorazepam is unsuitable or contraindicated (Max 100mg/24 hours)

For alternative antipsychotics to Haloperidol se notes in Appendix 1For doses in elderly:

See elderly guideline here

Reduce Lorazepam dose to 0.5mg- 1mg (max 2mg/24hr)

Reduce Haloperidol dose to 0.5-1mg (max 2mg/24hr)

Appendix 1 Prescribing information

Non response to rapid tranquilisation:

Obtain Consultant advice if more than 2 doses of IM Lorazepam or Haloperidol and 1 dose of IM Promethazine required
Consider Zuclopenthixol Acetate (Acuphase) on CONSULTANT advice only

Choice Therapy
Patient Group	Try First	Try Second	Max dose in first 24 hours
Highly aroused, physically robust adult including those already on antipsychotic drugs	Lorazepam 2mg	Repeat, then try Haloperidol 5mg	Lorazepam 4mg Haloperidol 12mg
Alcohol withdrawal	Use alcohol withdrawal guideline for Chlordiazepoxide
Acute disturbance due to medical condition or alcohol intoxication	Haloperidol 5mg
Psychotic agitation (acute disturbance due to a psychiatric illness)	Haloperidol	Lorazepam or Haloperidol	Haloperidol 20mg Lorazepam 8mg
Frail older people or severe respiratory disease	Haloperidol 2.5mg	Lorazepam 0.5-1mg	Haloperidol 10mg Lorazepam 4mg
Dementia with Lewy Bodies, Parkinson's disease	Lorazepam 0.5-1mg	Repeat	Lorazepam 4mg
Delirium	Haloperidol 2.5mg	Repeat	Haloperidol 10mg
Agitation/ behavioural disturbance in pregnancy	Haloperidol or Lorazepam or Promethazine as above

Choice of treatment:

A benzodiazepine is recommended as first line (if there is limited clinical information, antipsychotic naive, prolonged QTc)
Oral antipsychotic choice will depend on regular antipsychotic prescription and previous response to medication. Using an additional dose of an effective regular antipsychotic may be appropriate.
Promethazine is indicated for patients who are tolerant to benzodiazepines or who have had previous adverse drug reactions or who have previously abused/been addicted to benzodiazepines.
A baseline ECG is required for all patients prior to administration of Haloperidol (as per license) and is now contra-indicated in combination with other potentially QTc prolonging medication. If this is not possible, the risks and benefits of Haloperidol treatment should be documented clearly in notes.
A baseline ECG is required for all patients prior to administration of Zuclopenthixol Acetate

	Choice of IM Antipsychotic Medication
Drug	Dose	Information
Haloperidol	5mg IM, max 20mg/ 24 hours (adult)	Contra indicated in patients with prolonged QTc, patients with a history of dystonia with first generation antipsychotics and patients with Lewy body dementia
Olanzapine	Adult: 5-10mg IM, max 20mg/ 24 hour, max 3 injections in 24 hours Elderly: 2.5-5 mg IM max 20mg/ 24 hour, max 3 injections in 24 hours	Unlicensed product (imported from the EU)( document rationale for use clearly) Do not administer a benzodiazepine within 1 hour of administration Safer in Qtc prolongation and patients with a history of EPSE to first generation antipsychotics Under consultant psychiatrist advice only
Aripiprazole	9.75mg IM, repeated once in 24 hours	Safer in QTc prolongation, in combination with QTc prolonging medication and in patients with a history of Qtc prolongation/ arrhythmias Under consultant psychiatrist advice only

Risk Associated with IM rapid tranquilisation
Drug Class	Risk
Benzodiazepines	Loss of consciousness, respiratory depression or arrest, cardiovascular collapse in patients receiving Clozapine and paradoxical aggression.
Antipsychotics	Loss of consciousness, risk of sudden death (cardiac/respiratory complications), seizures, akathisia, dystonia, dyskinesia, NMS and excessive sedation
Antihistamines	Excessive sedation, painful injection, hypotension, arrhythmias, additional antimuscarinic effects

Post Rapid Tranquilisation Monitoring
Guideline	Post - RT parameters	Post - RT Monitoring	Additional Recommendations
Maudsley Prescribing Guidelines 12th edition (Taylor et al. 2015)	Temperature, pulse, blood pressure and respiratory rate	Every 10 minutes for 1 hour then half hourly until the patient is ambulatory	if monitoring of vital signs is not possible observe for symptoms of pyrexia, over sedation and general physical well being Resuscitation facilities must be made available

Management of problems resulting from the use of IM medication
Problem	Remedial Measure
Acute dystonic reaction	Procyclidine 5mg IM, repeat after 20 minutes if necessary, max 20mg/24 hours. Do not prescribe IM Haloperidol alone
Orthostatic hypotension	Lie patient flat, raise legs, monitor closely including regular BP measurement
Reduced respiratory rate (<10/minute or O²saturation < 90%)	Give Oxygen Give Flumazenil if Benzodiazepine induced. Initially 200 micrograms IV over 15 seconds, then 100 micrograms at 60 seconds. Maximum 1mg/24 hours
Abnormal physical observations	Continue to monitor regularly. Escalate to Ward Doctor. Record on NEWS chart and follow instructions with regard seeking medical assistance. Consider risk of neuroleptic malignant syndrome and arrhythmias in patients with a raised temperature.

Pharmacokinetics of IM medication
Drug	Time to peak concentration (T_max)	Elimination Half Life (T _1/2)
Haloperidol	20 minutes	20 hours
Lorazepam	60-90 minutes	12- 16 hours
Promethazine	2-3 hours	5-14 hours
Zuclopenthixol Acetate	36 hours	At 72 hours levels are 1/3 of max

QTc Off license information:

Haloperidol is contra-indicated in QT-interval prolongation. Co-prescription of Haloperidol with another QT interval prolonging drug should be avoided wherever possible; but if there are no appropriate clinical alternatives then the prescriber should document this use as unlicensed and appropriate monitoring agreed. NHS Borders ADTC supports this unlicensed use of haloperidol where the benefits of the treatment exceed the risks of treatment.

Promethazine has a conditional risk of QTc prolongation. The BAP guidelines recommend a combination of promethazine and haloperidol as a safe and effective method of rapid tranquilisation.

References

Patel et al. Joint BAP NAPICU evidence based consensus guidelines for the clinical management of acute disturbance: de-escalation and rapid tranquilisation. Journal of Psychopharmacology. 2018
Taylor et al. Maudsley Prescribing Guidelines. 12th edition. 2018.

Taylor et al. Maudsley Prescribing Guidelines. 13th Edition. 2018

Harwood. How to deal with violent and aggressive patients in acute medical settings. Journal of the Royal College of Physicians of Edinburgh. Volume 47: 2. June 2017.

BNF Online edition