What is the first line of treatment for psychosis?

First-Line Treatment for Psychosis

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

When to Initiate Treatment

• Begin antipsychotic treatment after 1 week or more of psychotic symptoms with associated distress or functional impairment 2
• Start immediately if severe distress exists or safety concerns to self or others are present 2
• Delay treatment only when symptoms are clearly substance-related or from medical conditions without safety concerns 2
• Rule out secondary causes of psychosis (CNS infections, traumatic brain injury, metabolic disturbances) before initiating psychiatric treatment 1

Specific First-Line Agents and Dosing

• Risperidone: Start at 2 mg/day (FDA trials showed efficacy at 2-6 mg/day, with most consistent positive responses at 4-6 mg/day) 1, 3
• Olanzapine: Start at 7.5-10 mg/day (FDA trials demonstrated efficacy at 10 mg/day for acute treatment) 1, 4
• No single antipsychotic agent is superior for efficacy—choice should be based on side-effect profile 2
• Avoid large initial doses as they increase side effects without hastening recovery 1, 2

Duration of Initial Trial

• Give a therapeutic dose for a minimum of 4 weeks before declaring treatment failure 1, 2
• Any immediate effects are likely due to sedation, with true antipsychotic effects becoming apparent after 1-2 weeks 1
• Implement treatment for 4-6 weeks using adequate dosages before determining efficacy 1

Adjunctive Treatment

• Short-term benzodiazepines (lorazepam 2 mg) may be added to antipsychotics to help stabilize acute agitation 1
• For cooperative patients, oral risperidone 2 mg plus lorazepam 2 mg is as effective as IM haloperidol plus lorazepam 4

Common Pitfalls to Avoid

• Do not switch antipsychotics before 4 weeks, as this is insufficient time to assess response 2
• Do not use excessive initial dosing, which causes unnecessary extrapyramidal symptoms and compromises future adherence 1, 2, 4
• Do not use long-acting injectable antipsychotics for acute treatment—these should only begin after improvement of acute symptoms 4
• Monitor for extrapyramidal side effects carefully, as these should be avoided to encourage future medication adherence 1

Evidence Supporting Atypical Antipsychotics as First-Line

• Real-world clinical trials demonstrate that risperidone 4 mg/day, olanzapine 15.3 mg/day, and haloperidol 5.4 mg/day show similar effectiveness (52-64% response rates), but atypical agents have significantly fewer extrapyramidal symptoms 5
• Olanzapine showed 67.2% clinical response versus 29.2% for haloperidol in first-episode psychosis, with statistically significant improvements in both positive and negative symptoms 6
• Atypical antipsychotics provide superior efficacy, reduced side effects, and better compliance compared to conventional agents 7