What is the appropriate management of acute psychosis, including immediate safety priorities, workup, and first‑line pharmacologic treatment?

Acute Psychosis Management

Immediate Safety Priorities

The first priority is to distinguish psychosis from delirium, as delirium is a medical emergency with twice the mortality if missed and requires fundamentally different management. 1

• Assess level of consciousness and orientation immediately – fluctuating consciousness, disorientation, and inattention indicate delirium rather than psychosis and demand urgent evaluation for underlying medical causes 1, 2
• Evaluate for life-threatening withdrawal states – alcohol or benzodiazepine withdrawal can present with psychotic symptoms but requires immediate benzodiazepine treatment to prevent seizures 3
• Screen for CNS infections, traumatic brain injury, and intracranial processes requiring urgent intervention 3, 2
• Test for asterixis and myoclonus to identify metabolic encephalopathy 3, 2
• Assess risk of self-harm or aggression to determine if hospitalization is required 4

Diagnostic Workup

Rule out secondary causes before attributing psychosis to a primary psychiatric disorder. 1

• Obtain baseline alcohol level and toxicology screening as the foundation for psychiatric evaluation 4
• Consider neuroimaging in new-onset psychosis to exclude structural lesions, particularly if focal neurological signs, head trauma history, or atypical features are present 3, 2
• Evaluate for medical conditions that can cause psychosis: endocrine disorders, autoimmune diseases, neoplasms, neurologic disorders, infections, metabolic disorders, nutritional deficiencies, and drug-related effects 1
• Perform focused neurological exam looking for focal deficits, catatonia, agitation, or abnormal movements 2

First-Line Pharmacologic Treatment

For Acute Agitation Requiring Rapid Tranquilization

The combination of haloperidol 5 mg IM plus lorazepam 2 mg IM is the established standard for rapid tranquilization of acutely agitated psychotic patients, achieving faster sedation than monotherapy. 4

• Alternative: Intramuscular ziprasidone 20 mg reduces agitation within approximately 15 minutes with sustained improvement for at least 4 hours and lower incidence of extrapyramidal side effects compared with haloperidol 4
• Short-term benzodiazepines as adjuncts to antipsychotics help stabilize the acute clinical situation 3, 4

For First-Episode Psychosis

In first-episode psychosis, the total dose of haloperidol (or equivalent antipsychotic) should not exceed 4–6 mg to minimize extrapyramidal adverse effects. 4

Transition to Oral Maintenance Therapy

Start with atypical antipsychotics as first-line treatment due to better tolerability and lower risk of extrapyramidal side effects that compromise long-term adherence. 3, 4

• Risperidone: Initial target dose of 2 mg/day 3, 4
• Olanzapine: Initial target dose of 7.5–10 mg/day 3, 4
• Avoid large initial doses – they increase side effects without hastening recovery; any immediate effects are due to sedation, with true antipsychotic effects appearing after 1–2 weeks 3, 4, 2

Treatment Duration and Response Assessment

Implement treatment for 4–6 weeks using adequate dosages before determining efficacy. 3, 4

• Dose escalation should occur only after 14–21 days if clinical response is inadequate, staying within tolerable limits for sedation and extrapyramidal symptoms 4
• Monitor closely for extrapyramidal side effects – avoiding these is critical to encourage future medication adherence 3, 4

If First Treatment Fails

If symptoms persist after 4–6 weeks or side effects are unmanageable, switch to a different antipsychotic with a different pharmacodynamic profile. 3, 4

• Consider amisulpride, paliperidone, or an alternative atypical agent if the first-line treatment was ineffective 3, 4
• Reassess the diagnosis and contributing factors after two adequate treatment trials (at least 4 weeks each) 3, 4

Treatment-Resistant Cases

Consider clozapine, as it is the only antipsychotic with documented superiority for treatment-refractory cases. 3, 4

• Use clozapine only after failure of at least two other antipsychotic agents (at least one being atypical) 3, 4
• Implement required monitoring protocols for agranulocytosis and seizures with clozapine 3

Psychosocial Interventions

Include families in the assessment process and treatment planning from the outset, providing emotional support and practical guidance. 3, 4, 2

• Provide psychoeducation to the patient about the illness, treatment options, relapse prevention, and risks of continued substance use 3
• Develop individualized crisis-support plans to facilitate recovery and treatment acceptance 4
• Ensure continuity of care with the same treating clinicians for at least 18 months 3, 4, 2

Hospitalization Criteria

Hospital admission is indicated when there is significant risk of self-harm or aggression, when community support is insufficient, or when the crisis exceeds the capacity of family caregivers to manage. 4

• When feasible, outpatient or home-based treatment is preferred if effective interventions can be provided in those environments 4

Critical Pitfalls to Avoid

• Don't miss delirium – fluctuating consciousness, disorientation, and inattention distinguish delirium from psychosis and require different urgent evaluation 3, 2
• Don't switch medications too early (before 4–6 weeks) or continue ineffective treatment too long 3, 4
• Don't abruptly discontinue antipsychotics after acute symptom resolution – maintain medication for 1–2 years after the initial episode given relapse risk 3
• Don't neglect side effect monitoring – this is a common reason for medication non-compliance, particularly in young adults 3, 4
• Don't delay neuroimaging in new-onset psychosis when focal neurological signs, head trauma history, or atypical features are present 2