Antipsychotic Dose Equivalents
The most evidence-based approach to antipsychotic dose equivalents uses 1 mg olanzapine as the reference standard, with the following conversions: risperidone 0.4 mg, haloperidol 0.7 mg, aripiprazole 1.4 mg, quetiapine 32.3 mg, ziprasidone 7.9 mg, amisulpride 38.3 mg, clozapine 30.6 mg, and chlorpromazine 38.9 mg. 1
Primary Dose Equivalents (Olanzapine 1 mg Reference)
The classical mean dose method, which analyzes actual doses used in flexible-dose trials, provides the most comprehensive equivalency data across second-generation antipsychotics 1:
Second-Generation Antipsychotics:
- Risperidone: 0.4 mg (equivalent to 1 mg olanzapine) 1
- Aripiprazole: 1.4 mg 1
- Quetiapine: 32.3 mg 1
- Ziprasidone: 7.9 mg 1
- Asenapine: 0.9 mg 1
- Clozapine: 30.6 mg 1
- Amisulpride: 38.3 mg 1
- Sertindole: 1.1 mg 1
- Zotepine: 13.2 mg 1
First-Generation Antipsychotics:
Alternative Reference Standards
Using Minimum Effective Dose Method
When using the minimum effective dose approach (based on fixed-dose placebo-controlled trials), the equivalents to 1 mg olanzapine are 2:
- Risperidone: 0.27 mg (2 mg minimum effective dose) 2
- Aripiprazole: 1.33 mg (10 mg minimum effective dose) 2
- Quetiapine: 20 mg (150 mg minimum effective dose) 2
- Ziprasidone: 5.33 mg (40 mg minimum effective dose) 2
- Lurasidone: 5.33 mg (40 mg minimum effective dose) 2
- Paliperidone: 0.4 mg (3 mg minimum effective dose) 2
- Asenapine: 1.33 mg (10 mg minimum effective dose) 2
- Clozapine: 40 mg (300 mg minimum effective dose) 2
- Haloperidol: 0.53 mg (4 mg minimum effective dose) 2
- Iloperidone: 1.07 mg (8 mg minimum effective dose) 2
- Sertindole: 1.60 mg (12 mg minimum effective dose) 2
Chlorpromazine Equivalents (Traditional Reference)
Using the conventional 100 mg chlorpromazine standard 3:
- Haloperidol: 2 mg 3
- Risperidone: 2 mg 3
- Olanzapine: 5 mg 3
- Quetiapine: 75 mg 3
- Ziprasidone: 60 mg 3
- Aripiprazole: 7.5 mg 3
Critical Dosing Considerations
Risperidone-Specific Warnings
Risperidone demonstrates a clear dose-response relationship where 2 mg daily is 50% less efficacious than 4 mg, making 4 mg the near-maximal effective dose for most patients. 4 However, in first-episode psychosis, maximum doses should not exceed 4 mg/day, as doses above 6 mg/day show no greater efficacy 5. Risperidone carries the highest risk of extrapyramidal symptoms among atypical agents, with effects potentially occurring at doses as low as 2 mg/day in elderly patients 5.
Quetiapine-Specific Warnings
Monitor for orthostatic hypotension and sedation during titration, as somnolence occurs in 17.5% of patients, with structured 4-day titration schedules designed specifically to minimize these risks. 6 Avoid combining quetiapine with benzodiazepines when possible, as fatalities have been reported with concurrent high-dose atypical antipsychotics and benzodiazepines 6.
Haloperidol Dosing Range
The near-maximal effective dose range for haloperidol is 3.3 to 10 mg daily, with no evidence that higher doses provide additional efficacy. 4 While high-dose first-generation antipsychotics are not less effective than medium doses, they should be avoided to prevent excessive toxicity 4.
Clozapine Requirements
Doses of clozapine well above 400 mg are necessary for optimal treatment of many schizophrenia patients. 4 Clozapine should only be used after failure of at least two therapeutic trials of other antipsychotics (at least one atypical) or development of significant side effects including tardive dyskinesia 7.
Methodological Considerations
The classical mean dose method (based on 75 studies with 16,555 participants) reflects actual clinical practice patterns from flexible-dose trials, making it highly applicable to real-world dosing 1. The minimum effective dose method provides more conservative estimates but is limited to drugs with adequate fixed-dose trial data 2. The DDD method covers 57 antipsychotics but lacks transparent methodology and should be used only when other methods are unavailable 8.
When switching between antipsychotics, use a gradual cross-titration approach informed by the half-life and receptor profile of each medication. 9 For depot formulations in adolescents with documented chronic symptoms and poor compliance, equivalency calculations apply only after establishing oral medication tolerance, though depot agents are not recommended for very early-onset schizophrenia 7.