What is the management of agitated patients with schizophrenia?

From the Guidelines

Management of agitated schizophrenic patients should prioritize the use of antipsychotic medication, such as olanzapine or risperidone, in conjunction with verbal de-escalation techniques and a calm environment, as recommended by the American Psychiatric Association 1. When managing agitated schizophrenic patients, it is essential to consider both pharmacological and non-pharmacological approaches. Initially, attempt verbal de-escalation in a calm, non-threatening environment with reduced stimuli.

• Verbal de-escalation techniques should be used as the first line of intervention
• A calm and non-threatening environment should be maintained to reduce stimuli If medication is needed, first-line options include second-generation antipsychotics like olanzapine (5-10mg orally or intramuscularly) or risperidone (2mg orally or 25-50mg intramuscularly as long-acting injection), as these have been shown to be effective in reducing symptoms of agitation 1.
• Olanzapine and risperidone are recommended as first-line options for managing agitation
• The dosage of these medications should be adjusted according to the patient's response and tolerance For severe agitation requiring rapid control, consider haloperidol 5mg with lorazepam 2mg intramuscularly, which can be repeated after 30-60 minutes if needed, as this combination has been shown to be effective in rapidly reducing agitation 1.
• Haloperidol and lorazepam can be used in combination for severe agitation
• The dosage and frequency of administration should be carefully monitored to avoid adverse effects Benzodiazepines like lorazepam (1-2mg) can be added for additional sedation, but their use should be carefully considered due to the risk of dependence and withdrawal 1.
• Benzodiazepines can be used for additional sedation, but their use should be carefully monitored
• The risk of dependence and withdrawal should be carefully considered when using benzodiazepines Monitor vital signs, level of consciousness, and for extrapyramidal side effects, as these can be significant concerns when using antipsychotic medications 1.
• Vital signs and level of consciousness should be closely monitored
• Extrapyramidal side effects should be carefully assessed and managed Once the acute agitation is controlled, transition to regular antipsychotic medication with appropriate dosing, and address underlying triggers such as psychosis, substance use, or medical conditions 1.
• Regular antipsychotic medication should be used to maintain control of symptoms
• Underlying triggers should be addressed to prevent future episodes of agitation Ensure patient and staff safety throughout by having adequate personnel present and removing potentially dangerous objects, as this is essential for preventing harm and promoting a safe environment 1.
• Patient and staff safety should be prioritized at all times
• Adequate personnel and a safe environment are essential for preventing harm After stabilization, develop a long-term treatment plan including regular antipsychotic medication, psychosocial interventions, and addressing comorbidities to prevent future episodes of agitation, as recommended by the American Psychiatric Association 1.
• A long-term treatment plan should be developed to prevent future episodes of agitation
• Regular antipsychotic medication, psychosocial interventions, and addressing comorbidities are essential components of this plan

From the FDA Drug Label

14 CLINICAL STUDIES

1. 3 Agitation Associated with Schizophrenia and Bipolar I Mania The efficacy of intramuscular olanzapine for injection for the treatment of agitation was established in 3 short-term (24 hours of IM treatment) placebo-controlled trials in agitated adult inpatients from 2 diagnostic groups: schizophrenia and bipolar I disorder (manic or mixed episodes)

14 CLINICAL STUDIES

1. 3 Acute Treatment of Agitation in Schizophrenia The efficacy of intramuscular ziprasidone in the management of agitated schizophrenic patients was established in two short-term, double-blind trials of schizophrenic subjects who were considered by the investigators to be “acutely agitated” and in need of IM antipsychotic medication

1 INDICATIONS & USAGE

Ziprasidone mesylate for injection, intramuscular is indicated for acute agitation in schizophrenic patients

Management of Agitated Schizophrenic Patients:

• Olanzapine (IM): is effective in the treatment of agitation associated with schizophrenia, with doses of 2.5 mg, 5 mg, 7.5 mg, and 10 mg being statistically superior to placebo on the PANSS Excited Component at 2 hours post-injection 2.
• Ziprasidone (IM): is indicated for the treatment of acute agitation in schizophrenic adult patients, with doses of 10 mg and 20 mg being statistically superior to a 2 mg control dose in reducing agitation 3 3.
• Key Considerations:
  • Olanzapine (IM) and ziprasidone (IM) are both effective options for managing agitation in schizophrenic patients.
  • The choice of medication should be based on individual patient needs and medical history.
  • It is essential to carefully evaluate the risks and benefits of each medication, including the potential for QT/QTc interval prolongation with ziprasidone 3.

From the Research

Management of Agitated Schizophrenic Patients

• Agitation in schizophrenia is a frequent and challenging symptom, characterized by heightened motor activity, emotional distress, and potential aggression 4, 5.
• Traditional treatments, including high-potency antipsychotics and benzodiazepines, remain first-line options but are associated with significant drawbacks such as sedation, extrapyramidal symptoms, tolerance, and limited applicability in certain patient populations 4, 5.
• Non-pharmacologic strategies like de-escalation techniques and environmental modifications are invaluable but may be impractical in acute care settings 4, 5.

Emerging Treatments

• Sublingual dexmedetomidine, recently FDA-approved, offers sedation without respiratory depression and a non-invasive administration route 4, 6.
• Subcutaneous olanzapine provides a more convenient alternative to intramuscular injections, reducing injection-related complications 4.
• Other emerging treatments such as gabapentin, pregabalin, and ketamine show promise in addressing agitation in specific contexts, including comorbid conditions and treatment-resistant cases 4, 5.
• Intranasal formulations of olanzapine are in development, offering the potential for favorable pharmacokinetics and onset of action combined with ease of delivery 7.

Treatment Approaches

• The level of agitation a patient is experiencing can determine the most appropriate treatment, with behavioral techniques sufficient for mild agitation and medication intervention needed for moderate to severe agitation 6.
• The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC or PEC) is a helpful instrument to assess where an individual is along the agitation spectrum 6.
• Short-acting intramuscular second-generation antipsychotic drugs, such as ziprasidone, olanzapine, and aripiprazole, are effective in reducing agitation in people with schizophrenia 8.