What is the first line of treatment for psychosis?

First-Line Treatment for Psychosis

The first-line treatment for psychosis is an atypical antipsychotic medication (such as risperidone 2 mg/day or olanzapine 7.5-10 mg/day) combined with psychosocial interventions, started at therapeutic doses and continued for a minimum of 4-6 weeks before assessing efficacy. 1, 2

Initial Treatment Selection and Dosing

Start with an atypical antipsychotic at a therapeutic dose immediately rather than titrating slowly from subtherapeutic doses, as this approach balances efficacy with tolerability. 1, 2

Recommended Starting Doses:

• Risperidone: 2 mg/day 1, 3
• Olanzapine: 7.5-10 mg/day 1, 3

These doses represent the evidence-based initial targets that optimize response while minimizing side effects. 1

Critical Dosing Principles:

• Avoid large initial doses, as they increase side effects without hastening recovery 1, 4, 2
• Maximum doses in first-episode psychosis should not exceed 4-6 mg haloperidol equivalent (approximately 4 mg risperidone or 20 mg olanzapine) 1
• Allow 4-6 weeks at therapeutic doses before declaring treatment failure, as antipsychotic effects typically become apparent after 1-2 weeks but full response takes longer 1, 4, 2

Why Atypical Antipsychotics Are First-Line

Atypical antipsychotics are preferred over typical antipsychotics because they are better tolerated even at low doses, which is critical for encouraging future medication adherence. 1 While typical antipsychotics may be equally efficacious for positive symptoms, extrapyramidal side-effects should be avoided to maintain long-term adherence. 1

The evidence shows no single atypical antipsychotic is superior for efficacy, so choice should be based on side-effect profile and patient preference. 2 However, the most robust data supports risperidone and olanzapine as having the most consistently positive responses across multiple trials. 5, 6

Essential Psychosocial Interventions

Adequate treatment requires combining antipsychotic medication with psychosocial interventions from the outset—this is not optional. 1

Core Psychosocial Components:

• Include families in the assessment and treatment plan, providing emotional support and practical advice, as families are typically in crisis at treatment initiation 1, 4
• Provide psychoeducation about the nature of psychosis, treatments, and expected outcomes 1
• Ensure continuity of care with the same treating clinicians for at least 18 months, as this critical period determines long-term outcomes 1, 3
• Implement supportive psychotherapy with active problem-solving orientation 1

Pre-Treatment Evaluation

Before initiating antipsychotic treatment, rule out medical emergencies and secondary causes of psychosis, including CNS infections, traumatic brain injury, substance-induced psychosis, and metabolic/endocrine disorders. 4, 3

Key Diagnostic Considerations:

• Distinguish psychosis from delirium—intact consciousness and orientation characterize psychosis, while fluctuating consciousness suggests delirium requiring different management 4
• Consider neuroimaging in new-onset psychosis to exclude intracranial processes requiring intervention 4
• Substance-induced psychosis (cannabis, methamphetamine) typically resolves within 30 days of abstinence and may not require long-term antipsychotic treatment 7

When to Switch or Escalate Treatment

If positive psychotic symptoms persist after 4-6 weeks at therapeutic doses with good adherence, switch to a different antipsychotic with a different pharmacodynamic profile. 4, 2

Treatment Algorithm:

1. First trial: Any atypical antipsychotic at therapeutic dose for 4-6 weeks 1, 2
2. Second trial: Different atypical antipsychotic for 4-6 weeks 2
3. Third trial: Clozapine after two adequate antipsychotic trials fail 1, 2

Do not switch antipsychotics before 4 weeks, as this is insufficient time to assess response. 3, 2 Do not delay clozapine after two adequate trials fail, as it is the only antipsychotic with proven superiority for treatment-resistant psychosis. 2

Monitoring Requirements

Document target symptoms before starting treatment and monitor systematically throughout. 1

Mandatory Monitoring:

• Extrapyramidal symptoms (should be avoided to encourage adherence) 1
• Weight gain and metabolic parameters 1
• Treatment response at regular intervals 1
• For clozapine: agranulocytosis and seizures 1, 2

Maintenance Phase Considerations

First-episode patients should receive maintenance antipsychotic treatment for 1-2 years minimum, given the high relapse risk (approximately 80% remain vulnerable to relapse in the first few years). 1

Additional improvement continues to occur over 6-12 months after acute symptoms are controlled, so patience is required before considering dose reduction. 2 Higher doses may be required during acute phases, with gradual reduction possible during residual phases, but this must be balanced against increased relapse risk. 1, 2

Common Pitfalls to Avoid

• Do not use excessive initial dosing—this causes unnecessary side effects without benefit 2
• Do not discharge from specialist care prematurely—the critical period extends up to 5 years after onset 1, 3
• Do not neglect family involvement—families require ongoing support and partnership in treatment planning 4, 3
• Do not miss delirium or withdrawal states—these require different urgent management than primary psychosis 4