What is the management of acute agitation in schizophrenia?

From the Guidelines

Management of acute agitation in schizophrenia requires a prompt, stepwise approach, starting with non-pharmacological interventions and proceeding to medication if necessary, with the goal of minimizing morbidity, mortality, and improving quality of life. The first-line pharmacological treatment is typically an antipsychotic, with or without a benzodiazepine, as supported by studies such as 1.

Non-Pharmacological Interventions

Before proceeding to medication, non-pharmacological interventions should be attempted, including:

• Verbal de-escalation techniques
• Providing a calm, quiet environment
• Using active listening and empathy to understand the patient's concerns

Pharmacological Treatment

If non-pharmacological interventions are ineffective, pharmacological treatment should be considered.

Oral Medication

Oral medication should be offered first if the patient is cooperative. Options include:

1. Risperidone 2mg orally, can be repeated after 2 hours if needed
2. Olanzapine 5-10mg orally, can be repeated after 2 hours if needed
3. Lorazepam 1-2mg orally, can be repeated after 1 hour if needed

Intramuscular (IM) Options

If oral medication is refused or ineffective, IM options include:

1. Haloperidol 5mg IM, can be repeated after 30-60 minutes if needed
2. Olanzapine 10mg IM, can be repeated after 2 hours if needed
3. Lorazepam 1-2mg IM, can be repeated after 1 hour if needed

Combination Therapy

Combination therapy, such as haloperidol 5mg IM plus lorazepam 2mg IM, can be considered for severe agitation, as suggested by studies like 1 and 1.

Monitoring and Adjustment

It is crucial to monitor vital signs, level of sedation, and watch for potential side effects such as extrapyramidal symptoms or respiratory depression. The patient should be reassessed frequently, and treatment adjusted as needed. Addressing the underlying cause of agitation with appropriate antipsychotic treatment is vital for long-term management, as noted in 1. Once the acute episode is controlled, the patient's regular antipsychotic regimen should be reviewed and optimized to prevent future episodes of agitation.

From the FDA Drug Label

2.4 Olanzapine for Injection: Agitation Associated with Schizophrenia and Bipolar I Mania Dose Selection for Agitated Adult Patients with Schizophrenia and Bipolar I Mania The efficacy of intramuscular olanzapine for injection in controlling agitation in these disorders was demonstrated in a dose range of 2.5 mg to 10 mg. The recommended dose in these patients is 10 mg. A lower dose of 5 or 7.5 mg may be considered when clinical factors warrant

The management of acute agitation in schizophrenia involves the use of intramuscular olanzapine.

• The recommended dose is 10 mg, with a lower dose of 5 or 7.5 mg considered when clinical factors warrant.
• The efficacy of olanzapine for injection in controlling agitation was demonstrated in a dose range of 2.5 mg to 10 mg.
• If agitation persists, subsequent doses up to 10 mg may be given, but the safety of total daily doses greater than 30 mg has not been evaluated.
• Patients requiring subsequent intramuscular injections should be assessed for orthostatic hypotension prior to administration of any subsequent doses 2.

From the Research

Management of Acute Agitation in Schizophrenia

The management of acute agitation in schizophrenia involves a range of treatment options, including non-pharmacologic behavioral and environmental de-escalation strategies, as well as biological treatment options such as pharmacologic agents and electroconvulsive therapy 3.

Pharmacologic Agents

Among pharmacologic agents, antipsychotics, benzodiazepines, anticonvulsants, and lithium have been studied in randomized trials 3. Atypical antipsychotics have the best evidence to support efficacy both in oral and short-acting intramuscular (IM) formulations, as well as in one instance in an inhalable formulation 3.

Treatment Options

Some of the treatment options for acute agitation in schizophrenia include:

• Intramuscular administration of antipsychotic medications and/or benzodiazepines 4, 5
• Inhaled loxapine powder, which is a rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia 4, 5
• Dexmedetomidine sublingual film, which is a recently approved treatment for acute agitation 5, 6
• Intranasal formulations of olanzapine, which are in development and offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery 5, 6

Alternative Approaches

Alternative approaches for addressing acute agitation in schizophrenia include the use of investigational drugs in early stages of their clinical development, such as dexmedetomidine film and intranasal olanzapine 6. These agents may become valuable options for the rapid management of acute agitation in patients who are willing to cooperate with medication therapy.

Efficacy and Tolerability

Rapid-acting intramuscular (IM) formulations of atypical antipsychotics have been shown to be at least as effective and better tolerated than IM haloperidol, with lower extrapyramidal side effects 7. Avoiding over-sedation is now recognised as important, and randomised clinical trial data indicate that some atypical antipsychotics have high dose-related sedative potential while others have low sedative potential 7.