Acutely disturbed or violent behaviour

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Questions and Answers

Rapid tranquilization is considered a first-line treatment for acutely disturbed behavior.

False

Sublingual asenapine has been shown to be less effective than placebo for managing acute agitation.

False

Inhaled loxapine requires patient cooperation and may lead to bronchospasm as a common side effect.

False

The efficacy of IM olanzapine is supported by large, placebo-controlled randomized controlled trials.

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The effectiveness of combining IM midazolam with IM haloperidol for agitation is less than using IM haloperidol alone.

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Studies typically demonstrate high levels of behavioral disturbance in patients treated with second-generation antipsychotics as monotherapy.

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The comparison of IM haloperidol with IM ziprasidone indicates that IM haloperidol is less effective than IM ziprasidone.

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The evidence base for pharmacological strategies in the management of acutely disturbed behavior has recently diminished.

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Zuclopenthixol acetate achieves peak plasma concentrations within 2 hours after administration.

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The duration of action for Zuclopenthixol acetate is directly related to the length of the ester carbon chain in the molecule.

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Sedation effects from Zuclopenthixol acetate are fully effective by 4 hours post-administration.

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In a comparative trial, Haloperidol produced fewer overall doses required than Zuclopenthixol acetate.

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The initial pharmacokinetic study of Zuclopenthixol acetate involved 19 participants.

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After 72 hours, plasma levels of Zuclopenthixol acetate were at about two-thirds of those at 36 hours.

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Significant reductions in psychotic symptoms were first observed in one study at 8 hours after administration of Zuclopenthixol acetate.

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Common adverse effects of Zuclopenthixol acetate include headache and nausea.

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Haloperidol has a 10% incidence of acute dystonia according to a meta-analysis.

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IV treatment of antipsychotics is commonly used and preferred over IM treatment.

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Droperidol is associated with a higher percentage of abnormal QTc changes compared to haloperidol.

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Large studies on IV olanzapine show a hypoxia occurrence rate of 17.7% in agitation cases.

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Higher doses of sedation are always more effective than lower doses for managing sedation in patients.

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IM midazolam dosages ranging from 7.5-15mg are less rapidly sedating than a combination of haloperidol and promethazine.

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Combining IV midazolam with IV olanzapine or droperidol provides a slower onset of sedation compared to using IV midazolam alone.

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A combination of haloperidol and promethazine is more effective and better tolerated than haloperidol alone.

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IM olanzapine remains effective compared to IM aripiprazole at both short (2 hours) and longer (24 hours) timeframes.

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IM droperidol is reported to be more effective than IM haloperidol in all evaluated circumstances.

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Cochrane reviews found that haloperidol-promethazine is effective for aggressive patients while haloperidol alone offers poor tolerability.

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The incidence of extrapyramidal symptoms (EPS) is reported to be higher with IM haloperidol compared to olanzapine.

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Resumption of aggression is reported to be more likely with haloperidol-promethazine than with olanzapine.

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Caution is not needed when applying the findings from this document to real-world clinical practice.

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IV droperidol is ineffective in managing disturbed and aggressive behaviors caused by psychosis.

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Combination treatments involving haloperidol and lorazepam are less effective in managing agitated patients compared to using either drug alone.

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Ketamine is suitable for risk treatment settings where intubation facilities are not readily available.

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Over 30% of patients receiving ketamine require intubation during sedation.

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Midazolam and droperidol are considered the slowest-acting treatments when administered intramuscularly.

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The primary aim of risk treatment (RT) is to minimize harm to others by maintaining a safe environment.

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Routine physical observations after RT are considered optional and can be disregarded.

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The combined use of multiple antipsychotics should be encouraged in risk treatment situations to ensure efficacy.

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Research on patients' experiences during risk treatment is extensive and well-documented.

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Zuclopenthixol Acetate is effective in achieving rapid tranquillisation in acutely psychotic patients.

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After an IM injection of Zuclopenthixol Acetate, it is recommended to wait at least 60 minutes to assess full response.

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In clinical studies, patients receiving Zuclopenthixol Acetate required a higher rate of repeat doses compared to those receiving haloperidol.

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Promethazine has a quick onset and is effective as a sedative.

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Sedation effects from Zuclopenthixol Acetate may not be observed until 8 hours post-administration.

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Cochrane reviews found that Zuclopenthixol Acetate demonstrated a rapid onset of action.

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Haloperidol is recommended for severe behavioral disturbances according to NICE.

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IV administration of lorazepam can be done every 5-10 minutes.

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Midazolam has no risk of causing respiratory depression.

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Monitoring of patients receiving parenteral antipsychotics is recommended more frequently than every hour after the first hour.

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ECG monitoring is advised for patients receiving haloperidol due to the risk of QT prolongation.

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Procyclidine is administered to manage acute dystonia.

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IM amylobarbitone is commonly used for rapid tranquilization.

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Monitoring patients' levels of consciousness after parenteral medication administration is not necessary.

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Lower doses of medication should be prescribed for children, adolescents, and older adults.

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IM treatment using Lorazepam should always include the presence of flumazenil.

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The combination of IM olanzapine and IM benzodiazepine is acceptable regardless of the patient's alcohol consumption.

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Administering a combination of haloperidol and lorazepam may be considered if single drug treatment fails.

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Promethazine at 50mg is regarded as a useful option in patients fully tolerant to benzodiazepines.

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Haloperidol is recommended as the first drug of choice in all situations of acute agitation.

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Diazepam can be administered at a rate of 10mg over a minimum of 5 minutes.

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Flumazenil should be administered only to patients with a respiratory rate of at least 10/min after receiving benzodiazepines.

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The maximum allowable dose of flumazenil in a 24-hour period is 2mg.

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Patients who have been receiving long-term benzodiazepines are safe to receive flumazenil without any risk.

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Monitoring of the respiratory rate is only required intermittently after administration of flumazenil.

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In cases of sedation where the respiratory rate does not return to normal, other causes should be investigated before ruling out flumazenil's effectiveness.

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Study Notes

### Acute Behavioral Disturbance

Acute behavioral disturbance can be caused by various factors like psychiatric illness, physical illness, substance abuse, or personality disorders.
Psychotic symptoms are frequent, and patients may act aggressively towards others.
Auditory, visual, or tactile hallucinations are common secondary symptoms.
Rapid tranquilization (RT) is a last resort treatment for acutely disturbed behavior when other approaches fail.
Patients often lack the capacity to provide informed consent, so randomized controlled trials (RCTs) with creative methodologies are used to evaluate the efficacy and safety of pharmacological treatments.

Oral and Inhaled Treatments

Multiple studies have investigated the effectiveness of second-generation antipsychotics (SGAs) administered orally.
These studies generally involved patients with moderate behavioral disturbance who readily agreed to treatment.
SGAs are often used as monotherapy, and the benefits of adding a second antipsychotic have not been established through RCTs.
Sublingual asenapine has been shown to be more effective than placebo for acute agitation.
Inhaled loxapine is effective for moderate agitation, supported by several RCTs and case series.
This method requires patient cooperation, and bronchospasm is a rare side effect.

Parenteral Treatment

Large, placebo-controlled RCTs support the efficacy of intramuscular (IM) olanzapine, ziprasidone, and aripiprazole for acute behavioral disturbance.
These trials indicate that IM olanzapine surpasses IM haloperidol, which in turn is superior to IM aripiprazole, which itself is superior to IM ziprasidone.
A substantial observational study suggests that IM olanzapine is effective and well-tolerated in clinical emergencies with severe disturbance.
Compared to IM haloperidol, a combination of IM midazolam and IM haloperidol demonstrates superior effectiveness in managing agitation during palliative care.
Numerous RCTs have explored the effectiveness of parenteral medications in acutely disturbed patients.

Zuclopenthixol Acetate (ZA)

Zuclopenthixol acetate (ZA), marketed as Acuphase, is a thioxanthene dopamine antagonist used in the UK and Europe.
It has an elimination half-life of approximately 20 hours.
Intramuscular (IM) injection yields a duration of action lasting 12-24 hours.
The duration of action depends on the length of the ester carbon chain in the molecule, with ZA decanoate having a longer-lasting effect due to slower release.

Pharmacokinetics and Clinical Effects of ZA

A pharmacokinetic study in 19 patients revealed that ZA was detectable in plasma after 1-2 hours, with peak concentrations reached around 36 hours post-administration.
Plasma levels decreased to about one-third at 72 hours compared to 36 hours.
The clinical effect was not immediate, with only 10 out of 17 patients showing minimal or no change in psychotic symptoms after 4 hours.
Sedation onset was observed at 4 hours, becoming fully effective by 72 hours.
A larger study involving 83 patients confirmed a pronounced and rapid reduction in psychotic symptoms, but the assessment was conducted more than 24 hours after administration, making the "rapid" effect somewhat uncertain.
Sedative effects were significant and measurable as early as 2 hours after administration.
Peak sedation was observed at 8 hours with a mean score of 2.2 (moderately sedated), decreasing to a mean score of 1.1 at 72 hours.
Common adverse effects included dystonia and rigidity.
Two independent studies corroborated ZA's slow onset and sustained effect, peaking at 24 hours and remaining evident at 72 hours.
A UK-based study showed a significant reduction in psychosis scores starting at 8 hours, continuing to decrease until the final measurement at 72 hours.

ZA Compared to Haloperidol

A comparative trial comparing ZA with IM/oral haloperidol and IM/oral zuclopenthixol base (multiple doses over 6 days) revealed that oral/IM preparations induced more sedation at 2 hours than ZA, but ZA's effect was more sustained.
No clear differences between the treatments were observed except for ZA's slower onset of action and lower overall dose requirement.
The number of doses varied across treatments: ZA (1-4), haloperidol (1-26), and zuclopenthixol (1-22).
This variable dose application can be considered a unique advantage of ZA.

Sedation and Agitation Control Instruments

This document discusses various instruments used for sedation and agitation control, primarily in a clinical setting, likely for patients with schizophrenia or other mental health conditions.

Key Sedation and Control Instrument Findings

IV Midazolam vs. Combinations:

Compared to IV midazolam alone, combining it with IV olanzapine or droperidol is more rapidly effective and reduces subsequent medication doses.
IM midazolam (7.5-15mg) is faster acting in inducing sedation than a combination of haloperidol (5-10mg) and promethazine (50mg).

IM Olanzapine vs. IM Haloperidol/Promethazine Combinations:

IM olanzapine (10mg) is similarly effective as IM haloperidol (10mg) and promethazine (25-50mg) in the short term, but the effects of the latter combination last longer.
A combination of haloperidol (5-10mg) and promethazine (50mg) is more impactful and better tolerated than haloperidol alone, leading to fewer dystonic reactions.
A combination of haloperidol (10mg) and promethazine (25-50mg) is more effective than lorazepam (4mg).

IM Chlorpromazine, Haloperidol, and Promethazine Combinations:

Combining IM chlorpromazine (100mg), haloperidol (5mg) and promethazine (25mg) offers no additional benefit compared to IM haloperidol (5mg) and promethazine (25mg).

IV Droperidol vs. Combinations:

A combination of IV midazolam and IV droperidol is faster in inducing sedation than IV droperidol or IV olanzapine alone.

IM Olanzapine vs. IM Aripiprazole:

IM olanzapine is more effective than IM aripiprazole in treating agitation in the short term (2 hours), but no difference is observed at 24 hours.

IM Midazolam Dosage Comparisons:

IM midazolam (5mg) is faster acting and more effective than olanzapine (10mg), ziprasidone (20mg), and both 5 and 10mg haloperidol in an emergency room study.

IM Haloperidol and Lorazepam:

A combination of IM haloperidol and IM lorazepam demonstrates similar efficacy to IM olanzapine in an open-label study.

IM Haloperidol vs. IM Droperidol:

IM droperidol and IM haloperidol are equally effective.

Cochrane Conclusions and Additional Notes:

Haloperidol alone is effective for acute behavioral disturbances, but it is poorly tolerated.
Co-administration of promethazine improves haloperidol tolerability, with promethazine being more beneficial than lorazepam.
NICE considers evidence regarding promethazine use for this purpose inconclusive.
Cochrane found haloperidol-promethazine effective for aggressive patients due to psychosis.
Resumption of aggression is more likely with olanzapine than with haloperidol-promethazine.
Data for aripiprazole is limited, but it may be more effective than placebo and haloperidol, but not olanzapine.
Olanzapine exhibits a lower incidence of EPS (Extrapyramidal Symptoms) compared to IM haloperidol.
Droperidol is effective in controlling severely disturbed and aggressive behaviors caused by psychosis, and its use is experiencing a resurgence.

General Caution:

Caution is advised when applying these findings to real-world clinical practice.

Haloperidol and Other Antipsychotics

This document discusses the use of haloperidol and other antipsychotic medications, particularly in emergency situations.

Key Points Regarding Haloperidol and Other Antipsychotics:

Tolerability of IM antipsychotics: A meta-analysis found a 5% incidence of acute dystonia with haloperidol, with other agents demonstrating better tolerability.
QTc prolongation: Haloperidol can prolong the QTc interval (15msec increase with 10mg). Promethazine may inhibit haloperidol metabolism and further increase this risk.
Droperidol: Associated with QT changes. In an observational study, only 1.28% patients who received droperidol had abnormal QTc.
Intravenous (IV) vs. Intramuscular (IM): IV treatment is rarely used but can be considered if benefits outweigh risks. A study comparing high-dose IV haloperidol and diazepam found both effective at 24 hours.
IV Olanzapine: Large studies show IV olanzapine for agitation is often effective, but potential for hypoxia (17.7% of cases) and the need for intubation should be considered.
High-dose sedation: High doses of sedation (haloperidol, droperidol or midazolam >10mg) are not more effective than lower doses and lead to more adverse effects.
Low-dose haloperidol: Small RCTs suggest low-dose haloperidol is effective when used with midazolam.
Midazolam: Used in a PICU setting. Higher doses can cause over-sedation and respiratory depression. Lorazepam and midazolam (7.5-15mg) can be effective for psychosis-induced aggression.

Ketamine and Other Sedative Agents

This document discusses the use of ketamine and other sedative agents for managing agitated patients, particularly in the context of risk treatment (RT).

Sedation in Patients with Behavioral Disturbances

Combination treatments (most commonly haloperidol 5mg and lorazepam 2mg) are more effective in reducing the need for subsequent sedation compared to using either drug alone. A study with IV sedation in patients intoxicated with alcohol observed this.
Haloperidol proved effective and well-tolerated in managing behavioral disturbances associated with PCP consumption.

Ketamine

Ketamine is commonly employed in hospital emergency departments for agitation.
A systematic review found that, on average, 315mg IM ketamine achieved adequate sedation within 7.2 minutes.
Over 30% of 650 patients receiving ketamine eventually required intubation, and more than 1% experienced laryngospasm.
Ketamine is likely unsuitable for RT settings where intubation facilities are not readily available.
Midazolam and droperidol are considered the fastest-acting single intramuscular treatments, and haloperidol use alone should be avoided, possibly even in combination.
Second- or third-line treatments often involve a combination of benzodiazepines and antipsychotics or intravenous benzodiazepines followed by ketamine (2-5mg/kg IM).

Practical Measures for Risk Treatment (RT)

Management plans should be developed in advance to prevent disturbed behavior and reduce violence risk.
Nursing interventions like de-escalation, time-out, seclusion, increased nursing levels, transfer to a psychiatric intensive care unit (PICU), and pharmacological management are options.
High cumulative doses of antipsychotics should be avoided.
Routine physical observations after RT are crucial.
Research on patients' experiences during RT is limited, and RT may be perceived as punitive by patients.

Goals of Risk Treatment (RT)

Goals of RT include:
- Reducing patient suffering (psychological or physical, such as through self-harm or accidents).
- Minimizing harm to others by maintaining a safe environment.
- Preventing harm to the patient by prescribing safe medication regimens and monitoring physical health.

Important Note Regarding Polypharmacy

The combined use of multiple antipsychotics (polypharmacy) should be avoided due to the risk of QT prolongation, a common adverse effect of many antipsychotics. This is particularly important in RT situations where the patient's physical state may predispose them to cardiac arrhythmias.

Rapid Tranquilization Summary (Continued)

c. Promethazine: Has a slow onset but is often effective as a sedative. Dilution is not required before IM injection. It can be repeated up to a maximum of 100mg/day. After injection, wait 1-2 hours to assess response. Note: Promethazine alone has been reported to cause Neuroleptic Malignant Syndrome (NMS), though rarely. It has a weak dopamine antagonist effect. Pharmacokinetic interaction with haloperidol is possible (reduced metabolism of haloperidol), increasing risk with repeated doses.
d. Haloperidol: Recommended by NICE only for moderate behavioral disturbances. Large observational studies support its efficacy in clinical emergencies.
e. Diazepam/Lorazepam/Midazolam: Diazemuls are preferred to avoid injection site reactions. Lorazepam and Midazolam can also be administered intravenously (IV). IV administration is recommended for a rapid effect avoiding delayed absorption issues with IM, and repeated doses can be given every 5-10 minutes. Midazolam can cause respiratory depression.
f. Other Options: IM ketamine is becoming increasingly popular. IM amylobarbitone and IM paraldehyde are rarely used due to difficulty obtaining them and potential adverse effects. IV olanzapine, IV droperidol, and IV haloperidol are possible but have fairly common adverse effects. ECT is also an option.

Rapid Tranquilization - Physical Monitoring

After any parenteral drug administration, monitor:
- Temperature
- Pulse
- Blood Pressure
- Respiratory Rate
Monitor vital signs every 15 minutes for 1 hour and then hourly until the patient is ambulatory.
Patients who refuse monitoring or can't be approached due to behavioral disturbances must be observed for signs of pyrexia, hypoxia, hypotension, over-sedation and general well-being.
Continuously monitor oxygen saturation using pulse oximetry if the patient is asleep or unconscious.
ECG and haematological monitoring are also recommended, especially when parenteral antipsychotics at higher doses are administered.
Patients are at risk of cardiac arrhythmias (QT prolongation) when receiving haloperidol, so formal ECG monitoring is recommended.

Remedial Measures in Rapid Tranquilization

Problem	Remedial Measures
Acute dystonia (including oculogyric crises)	Give procyclidine 5-10mg IM or IV
Reduced respiratory rate (bradypnea)	Consider flumazenil 0.2mg IV (repeat as required in increments of 0.2mg every 2-3 minutes up to a maximum of 1mg). If bradycardia is suspected, monitor pulse closely
Overt sedation	Stop treatment and monitor closely. Consider using a benzodiazepine antagonist (flumazenil) after stopping the benzodiazepine/midazolam. Only 10% of the dose given will be reversed
Hypotension	Raise the head of the bed and administer fluids

Zuclopenthixol Acetate (Acuphase)

ZA is not a rapidly tranquillising agent.
A double-blind study involved participants receiving either ZA or haloperidol IM, assessed over three days. Changes in BPRS and CGI scores were similar. Only one of 23 ZA patients needed a second injection, compared to 7 of 21 haloperidol patients needing a repeat dose.
Thai researchers found similar results in three studies with moderate sample sizes (n=44, n=40, n=50).
A Cochrane review concluded that ZA did not have a rapid onset of action and the studies were methodologically flawed.
The utility of ZA in rapid tranquillisation is limited by a delayed onset of sedative and antipsychotic actions.
Sedation may be apparent in some patients after 2-4 hours, but antipsychotic effects are seen only after 8 hours.
If given to a restrained patient, their behaviour will likely remain unchanged for several hours.
ZA reduces the need for restraints for IM injections but has no role in rapid tranquillisation.
ZA should be used only after an acutely psychotic patient has required repeated injections of short-acting antipsychotics (e.g., haloperidol, olanzapine) or sedative drugs (e.g., lorazepam).
It is potentially best reserved for patients who have responded well to ZA in prior situations.
Allow 15 minutes after IV injection, or 60 minutes after IM injection before assessing the full response to the drug.
ZA should never be used for rapid tranquillisation, for patients who physically resistant, or neuroleptic-naïve patients due to prolonged EPSE risk.

Rapid Tranquillization Summary

In an emergency situation, assess if there might be a medical cause.
Optimize regular prescription.
The aim of pharmacological treatment is to calm the patient, but not to oversedate.
Lower doses should be used for children, adolescents, and older adults.
Monitor patients' levels of consciousness and physical health after parenteral medication administration (see protocol).

Step Intervention for Rapid Tranquillization

De-escalation: Time out, placement, etc., as appropriate.
Offer oral treatment
- If patient is prescribed a regular antipsychotic:
  - Lorazepam 1-2mg
  - Promethazine 25-50mg
  - Monotherapy with buccal midazolam may avoid the need for IM treatment. Dose: 10mg. Note that this preparation is unlicensed.
- If patient is not already taking a regular oral or depot antipsychotic:
  - Olanzapine 10mg or
  - Risperidone 1-2mg or
  - Quetiapine 50-100mg or
  - Haloperidol 5mg (best with promethazine 25mg). Note that the EU SPC for haloperidol recommends a pre-treatment ECG and to avoid concomitant antipsychotics.
Consider IM treatment
- Lorazepam 2mg
- Have flumazenil on hand in case of benzodiazepine-induced respiratory depression.
- Promethazine 50mg (IM promethazine is a useful option in a benzodiazepine-tolerant patient).
- Olanzapine 10mg (IM olanzapine should NOT be combined with an IM benzodiazepine, particularly if alcohol has been consumed).
- Aripiprazole 9.75mg (Less hypotension than olanzapine, but less effective).
- Haloperidol 5mg (Haloperidol should be the last drug considered. The incidence of acute dystonia is high; combine with IM promethazine and ensure IM procyclidine is available). Pre-treatment ECG required. Repeat after 30-60 minutes if insufficient effect. Combinations of haloperidol and lorazepam or haloperidol and promethazine may be considered if single drug treatment fails. Drugs must not be mixed in the same syringe. IM olanzapine must never be combined with IM benzodiazepine.
Consider IV treatment
- Diazepam 10mg over at least 2 minutes.
- Repeat after 5-10 minutes if insufficient effect (up to 3 times).
- Have flumazenil on hand.
Seek expert advice
- Consider transfer to the medical unit for administration of IM ketamine.

Notes Regarding Rapid Tranquilization Protocol

a. Carefully check administration and dilution instructions (vary between manufacturers. Many centres use 4mg. An alternative is IM midazolam 5-15mg, 5mg is usually sufficient. The risk of respiratory depression is dose-related with both drugs but generally greater with midazolam).
b. Caution in the very young and elderly and those with pre-existing brain damage or impulse control problems, as disinhibition reactions are more likely.

Remedial Measures in Rapid Tranquillization (Continued)

Irregular or slow pulse: Monitor blood pressure closely.
Slow heart rate (bradycardia): Check ECG rhythm.
Irregular or slowed heart rate (bradycardia) alongside decreased blood pressure: Monitor carefully. Consider using a benzodiazepine antagonist (flumazenil).
Hypotension (30mmHg orthostatic drop or < 50mmHg diastolic):
- Increased temperature.
- Refer to specialist medical care immediately.
- Have patient lie flat, tilt bed towards head.
- Monitor closely. (risk of NMS and perhaps arrhythmia).
- Check creatine kinase urgently.

Guidelines for the use of flumazenil

Indication for use: If, after the administration of lorazepam, midazolam or diazepam, respiratory rate falls below 10/min.

Contraindications

Patients with epilepsy receiving long-term benzodiazepine treatment

Caution

Carefully titrate dosage in patients with hepatic impairment

Dose and Route of Administration

Initial dose: 200µg intravenously over 15 seconds
Subsequent dose: 100µg intravenously over 15 seconds, if required level of consciousness is not achieved after initial dose.
Max 60 seconds between doses

Time Before Dose Can be Repeated

1mg in 24 hours (one initial dose and eight subsequent doses)

Maximum Dose

1mg in 24 hours

Side Effects

Agitation, anxiety, or fear upon awakening
Seizures may occur in regular benzodiazepine users
Usually subside

Monitoring

Respiratory rate should be continuously monitored until it returns to baseline levels.
Flumazenil has a short half-life, so respiratory function may recover and then deteriorate again.
If respiratory rate does not return to normal after initial doses, consider alternative causes for sedation.

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This quiz explores the efficacy and effectiveness of various pharmacological treatments for managing acutely disturbed behavior. It covers medications such as asenapine, loxapine, olanzapine, midazolam, haloperidol, and ziprasidone, comparing their effectiveness and side effects. Test your knowledge on recent studies and findings in the field.

Acutely disturbed or violent behaviour

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Questions and Answers

Rapid tranquilization is considered a first-line treatment for acutely disturbed behavior.

Sublingual asenapine has been shown to be less effective than placebo for managing acute agitation.

Inhaled loxapine requires patient cooperation and may lead to bronchospasm as a common side effect.

The efficacy of IM olanzapine is supported by large, placebo-controlled randomized controlled trials.

The effectiveness of combining IM midazolam with IM haloperidol for agitation is less than using IM haloperidol alone.

Studies typically demonstrate high levels of behavioral disturbance in patients treated with second-generation antipsychotics as monotherapy.

The comparison of IM haloperidol with IM ziprasidone indicates that IM haloperidol is less effective than IM ziprasidone.

The evidence base for pharmacological strategies in the management of acutely disturbed behavior has recently diminished.

Zuclopenthixol acetate achieves peak plasma concentrations within 2 hours after administration.

The duration of action for Zuclopenthixol acetate is directly related to the length of the ester carbon chain in the molecule.

Sedation effects from Zuclopenthixol acetate are fully effective by 4 hours post-administration.

In a comparative trial, Haloperidol produced fewer overall doses required than Zuclopenthixol acetate.

The initial pharmacokinetic study of Zuclopenthixol acetate involved 19 participants.

After 72 hours, plasma levels of Zuclopenthixol acetate were at about two-thirds of those at 36 hours.

Significant reductions in psychotic symptoms were first observed in one study at 8 hours after administration of Zuclopenthixol acetate.

Common adverse effects of Zuclopenthixol acetate include headache and nausea.

Haloperidol has a 10% incidence of acute dystonia according to a meta-analysis.

IV treatment of antipsychotics is commonly used and preferred over IM treatment.

Droperidol is associated with a higher percentage of abnormal QTc changes compared to haloperidol.

Large studies on IV olanzapine show a hypoxia occurrence rate of 17.7% in agitation cases.

Higher doses of sedation are always more effective than lower doses for managing sedation in patients.

IM midazolam dosages ranging from 7.5-15mg are less rapidly sedating than a combination of haloperidol and promethazine.

Combining IV midazolam with IV olanzapine or droperidol provides a slower onset of sedation compared to using IV midazolam alone.

A combination of haloperidol and promethazine is more effective and better tolerated than haloperidol alone.

IM olanzapine remains effective compared to IM aripiprazole at both short (2 hours) and longer (24 hours) timeframes.

IM droperidol is reported to be more effective than IM haloperidol in all evaluated circumstances.

Cochrane reviews found that haloperidol-promethazine is effective for aggressive patients while haloperidol alone offers poor tolerability.

The incidence of extrapyramidal symptoms (EPS) is reported to be higher with IM haloperidol compared to olanzapine.

Resumption of aggression is reported to be more likely with haloperidol-promethazine than with olanzapine.

Caution is not needed when applying the findings from this document to real-world clinical practice.

IV droperidol is ineffective in managing disturbed and aggressive behaviors caused by psychosis.

Combination treatments involving haloperidol and lorazepam are less effective in managing agitated patients compared to using either drug alone.

Ketamine is suitable for risk treatment settings where intubation facilities are not readily available.

Over 30% of patients receiving ketamine require intubation during sedation.

Midazolam and droperidol are considered the slowest-acting treatments when administered intramuscularly.

The primary aim of risk treatment (RT) is to minimize harm to others by maintaining a safe environment.

Routine physical observations after RT are considered optional and can be disregarded.

The combined use of multiple antipsychotics should be encouraged in risk treatment situations to ensure efficacy.

Research on patients' experiences during risk treatment is extensive and well-documented.

Zuclopenthixol Acetate is effective in achieving rapid tranquillisation in acutely psychotic patients.

After an IM injection of Zuclopenthixol Acetate, it is recommended to wait at least 60 minutes to assess full response.

In clinical studies, patients receiving Zuclopenthixol Acetate required a higher rate of repeat doses compared to those receiving haloperidol.

Promethazine has a quick onset and is effective as a sedative.

Sedation effects from Zuclopenthixol Acetate may not be observed until 8 hours post-administration.

Cochrane reviews found that Zuclopenthixol Acetate demonstrated a rapid onset of action.

Haloperidol is recommended for severe behavioral disturbances according to NICE.

IV administration of lorazepam can be done every 5-10 minutes.

Midazolam has no risk of causing respiratory depression.

Monitoring of patients receiving parenteral antipsychotics is recommended more frequently than every hour after the first hour.

ECG monitoring is advised for patients receiving haloperidol due to the risk of QT prolongation.

Procyclidine is administered to manage acute dystonia.

IM amylobarbitone is commonly used for rapid tranquilization.

Monitoring patients' levels of consciousness after parenteral medication administration is not necessary.

Lower doses of medication should be prescribed for children, adolescents, and older adults.

IM treatment using Lorazepam should always include the presence of flumazenil.

The combination of IM olanzapine and IM benzodiazepine is acceptable regardless of the patient's alcohol consumption.

Administering a combination of haloperidol and lorazepam may be considered if single drug treatment fails.

Promethazine at 50mg is regarded as a useful option in patients fully tolerant to benzodiazepines.

Haloperidol is recommended as the first drug of choice in all situations of acute agitation.

Diazepam can be administered at a rate of 10mg over a minimum of 5 minutes.

Flumazenil should be administered only to patients with a respiratory rate of at least 10/min after receiving benzodiazepines.

The maximum allowable dose of flumazenil in a 24-hour period is 2mg.

Patients who have been receiving long-term benzodiazepines are safe to receive flumazenil without any risk.

Monitoring of the respiratory rate is only required intermittently after administration of flumazenil.

In cases of sedation where the respiratory rate does not return to normal, other causes should be investigated before ruling out flumazenil's effectiveness.

Study Notes

Oral and Inhaled Treatments

Parenteral Treatment

Zuclopenthixol Acetate (ZA)

Pharmacokinetics and Clinical Effects of ZA

ZA Compared to Haloperidol

Sedation and Agitation Control Instruments

Key Sedation and Control Instrument Findings

IV Midazolam vs. Combinations:

IM Olanzapine vs. IM Haloperidol/Promethazine Combinations:

IM Chlorpromazine, Haloperidol, and Promethazine Combinations: