What medications are used to treat acute psychosis?

Medications for Acute Psychosis

Atypical antipsychotics should be used as first-line treatment for acute psychosis, with risperidone 2 mg/day or olanzapine 7.5-10 mg/day as recommended initial target doses. 1, 2

First-Line Pharmacological Treatment

Atypical antipsychotics are preferred over typical antipsychotics due to better tolerability and lower risk of extrapyramidal side effects (EPS), even though both classes have similar efficacy for positive symptoms. 1, 2 The British Journal of Psychiatry guidelines emphasize that avoiding EPS is critical for encouraging future medication adherence. 1

Recommended Starting Doses

• Risperidone: 2 mg/day 1, 2, 3
• Olanzapine: 7.5-10 mg/day 1, 2
• Quetiapine: 300-600 mg/day (for bipolar-related psychosis) 4

Dosing Principles

Avoid large initial doses—they do not hasten recovery but significantly increase side effects. 2 The American Academy of Child and Adolescent Psychiatry explicitly warns against excessive initial dosing. 2

Antipsychotic effects become apparent after 1-2 weeks, not immediately; any immediate effects are due to sedation alone. 2 This is a critical pitfall—clinicians should not interpret early sedation as therapeutic response and prematurely escalate doses.

After initial titration, dose increases should occur only at widely spaced intervals (14-21 days) if response is inadequate, and only within the limits of sedation and EPS emergence. 1

Adjunctive Medications

Short-term benzodiazepines may be used as adjuncts to antipsychotics to help stabilize the acute clinical situation. 2 This combination has been standard practice for managing acute agitation alongside antipsychotic treatment. 5, 6

Maximum Doses in First-Episode Psychosis

For first-episode psychosis, maximum doses should generally not exceed 4-6 mg haloperidol equivalent, which translates to approximately 4 mg/day risperidone or 20 mg/day olanzapine. 1 Higher doses in antipsychotic-naive patients dramatically increase EPS risk without improving efficacy.

Treatment Duration Before Assessing Efficacy

Implement treatment for 4-6 weeks using adequate dosages before determining efficacy. 2 Switching medications too early (before 4 weeks) is a common pitfall that prevents adequate therapeutic trials. 2

If First Treatment Fails

If no response after 4-6 weeks or if side effects are unmanageable, switch to a different antipsychotic with a different pharmacodynamic profile. 2 For example, if a D2 partial agonist (aripiprazole, brexpiprazole) fails, consider switching to risperidone, paliperidone, olanzapine, or amisulpride. 2

Before switching, reassess the diagnosis and review reasons for treatment failure, including adherence, substance use, and psychosocial stressors. 1, 2

Treatment-Resistant Cases

If positive symptoms remain significant after two adequate treatment trials (at least 4 weeks each with different antipsychotics), consider clozapine. 2 Clozapine is the only antipsychotic with documented superiority for treatment-refractory schizophrenia. 2 At least one of the failed trials should have been with an atypical antipsychotic. 2

Intramuscular Formulations for Acute Agitation

For severely agitated patients requiring immediate intervention, intramuscular formulations of olanzapine, ziprasidone, or haloperidol are available. 5, 6 These short-acting IM preparations achieve rapid symptom control while minimizing the need for physical restraints. 5, 6

Essential Pre-Treatment Assessment

Before initiating antipsychotic treatment, rule out physical illnesses and medical conditions that can cause psychosis, including CNS infections, traumatic brain injury, endocrine disorders, and substance intoxication/withdrawal. 1, 2 The American College of Radiology recommends considering neuroimaging in new-onset psychosis to exclude intracranial processes requiring intervention. 1, 2

Common Pitfalls to Avoid

• Don't use excessive initial doses expecting faster response—this only increases side effects 2
• Don't switch medications before 4-6 weeks unless side effects are intolerable 2
• Don't neglect monitoring for EPS, which is the primary reason for medication non-adherence 1, 2
• Don't discontinue antipsychotics abruptly after acute symptom resolution—maintenance therapy prevents relapse 2
• Don't delay treatment until a crisis develops (self-harm, violence)—early intervention improves outcomes 2

Transition to Maintenance Phase

The recuperative phase occurs after 4-12 weeks if the acute phase is controlled; maintain antipsychotic medication during this period as additional improvement may occur over 6-12 months. 2 Consider gradual dose reduction to decrease side effects, especially if high doses were needed for acute control. 2

Family Involvement

Include families in the assessment process and treatment planning from the outset; provide emotional support and practical advice as families are typically in crisis at treatment initiation. 1, 2 Progressively educate families about the nature of psychosis, treatments, and expected outcomes. 1, 2