Treatment of Psychosis
Start with a second-generation (atypical) antipsychotic at low doses—specifically risperidone 2 mg/day or olanzapine 7.5-10 mg/day—as first-line treatment for acute psychosis. 1, 2
Initial Pharmacological Management
First-Line Antipsychotic Selection and Dosing
Begin with atypical antipsychotics due to superior tolerability and lower risk of extrapyramidal symptoms compared to typical antipsychotics. 1, 2
For risperidone: Start at 2 mg/day (target dose), with a maximum of 4 mg/day in first-episode patients. 2
For olanzapine: Start at 7.5-10 mg/day (target dose), with a maximum of 20 mg/day in first-episode patients. 2, 3
Avoid large initial doses—they do not hasten recovery but significantly increase side effects, particularly extrapyramidal symptoms that compromise future medication adherence. 1
Critical Timing Considerations
Implement treatment for 4-6 weeks at adequate dosages before determining efficacy. 1
Any immediate effects within the first 1-2 weeks are likely due to sedation; true antipsychotic effects become apparent after 1-2 weeks. 1
If dose adjustment is needed, increase only at widely spaced intervals (14-21 days after initial titration) to minimize extrapyramidal side effects. 2
Adjunctive Therapy
Short-term benzodiazepines may be added to antipsychotics to help stabilize the acute clinical situation. 1
For intramuscular treatment in emergency settings: haloperidol 2-5 mg IM or olanzapine 10 mg IM as monotherapy, or haloperidol 5 mg IM plus lorazepam 2 mg IM for more rapid sedation. 4
Algorithm for Treatment Failure
After First Antipsychotic Trial (4-6 Weeks)
If no response after 4-6 weeks or if side effects are unmanageable, switch to a different antipsychotic with a different pharmacodynamic profile. 1
- For patients whose first-line treatment was a D2 partial agonist, consider amisulpride, risperidone, paliperidone, or olanzapine as second-line treatment. 1
After Two Failed Trials (Treatment-Resistant Psychosis)
If positive symptoms remain significant after two adequate treatment trials (at least 4-6 weeks each at therapeutic doses), reassess the diagnosis and contributing factors before proceeding. 5, 1
Criteria for Treatment-Resistant Psychosis
Each treatment episode must last at least 6 weeks at a therapeutic dose (minimum 600 mg chlorpromazine equivalents daily or manufacturer's recommended target dose). 5
Failure of at least two adequate treatment episodes with different antipsychotic drugs is required to establish treatment resistance. 5
The minimum total duration of treatment required is 12 weeks (two 6-week trials). 5
Clozapine for Treatment-Resistant Cases
Consider clozapine for treatment-resistant cases—it is the only antipsychotic with documented superiority for treatment-refractory schizophrenia. 1
Clozapine should be used only after failure to respond to at least two therapeutic trials of other antipsychotic agents (at least one being an atypical antipsychotic). 1
Clozapine requires close monitoring due to severe adverse effects. 6
Transition to Maintenance Phase
The recuperative phase occurs after 4-12 weeks if the acute phase is controlled. 1
Maintain antipsychotic medication during this period as additional improvement may occur over 6-12 months. 1
Consider gradual dose reduction to decrease side effects, especially if high doses were needed for acute control. 1
Critical Pitfalls to Avoid
Medication Selection Errors
Do not use typical antipsychotics (e.g., haloperidol) as first-line treatment for non-emergency psychosis due to higher risk of extrapyramidal side effects. 2
If typical antipsychotics must be used, maximum dose should be 4-6 mg/day haloperidol in first-episode psychosis. 2
Do not use long-acting injectable antipsychotics for acute treatment—they lack dosage flexibility needed during the acute phase. 4
Timing Errors
Do not switch medications too early (before 4-6 weeks) or continue ineffective treatment too long. 1
Do not abruptly discontinue antipsychotics after acute symptom resolution—maintenance therapy prevents relapse (approximately 60% relapse rate without medication vs. less than 20% with prophylactic treatment). 7
Dosing Errors
Avoid excessive initial dosing which leads to unnecessary side effects without improving efficacy. 1, 2
Monitor closely for extrapyramidal side effects, which should be avoided to encourage future medication adherence. 1
Assessment Failures
Before initiating psychiatric treatment, rule out secondary causes of psychosis including:
Central nervous system infections, traumatic brain injury, and other neurologic conditions. 1, 8
Substance-induced psychosis (cannabis, methamphetamine)—these typically resolve within 30 days of abstinence. 6
Medical conditions such as dementia or other primary neurologic causes. 6
If positive symptoms persist after trials of two first-line atypical antipsychotics, review reasons for treatment failure including:
Medication adherence issues. 2
Substance misuse. 2
Underlying medical conditions. 2
Family stresses and psychosocial factors. 2