| Agent | Initial dose
(mg/day) | Usual dose range
(mg/day) | Maximum dose
(mg/day) | Half-life
(hours) | Metabolism and clearance | Selected characteristics |
| Aripiprazole | 5 to 10 | 10 to 15 | 30 | 74 | CYP2D6 and 3A4 to active and inactive metabolites | - Partial dopamine agonist
- May adjust daily dose by 5 to 10 mg increments every 3 to 5 days
- Variable dose requirements due to CYP2D6 metabolizer phenotype
- Dose adjustment may be needed with CYP2D6 and/or 3A4 inhibitors or inducers*
- Other formulations: ODT, orally dispersible film, oral solution, LAI
|
| Asenapine, sublingual | 10 | 10 to 20 | 20 | 24 | CYP1A2 and glucuronidation to inactive metabolite | - Daily dose administered in 2 divided doses
- May adjust daily dose by 10 mg after 7 days per labeling; however, some patients may require adjustment sooner (eg, after 3 or 4 days)
- Tablets are for SL use; poorly bioavailable if swallowed
- Rapid SL absorption; maximum concentration within approximately 1 hour
- Avoid use in advanced cirrhosis
|
| Asenapine, transdermal patch | 3.8 mg/24 hours | 3.8 to 7.6 mg/24 hours | 7.6 mg/24 hours | 30 | CYP1A2 and glucuronidation to inactive metabolite | - Available patch strengths: 3.8, 5.7, 7.6 mg/24 hours
- 3.8 mg/24 hours patch approximately equal 5 mg SL twice daily
- 7.6 mg/24 hours patch approximately equal 10 mg SL twice daily
- May adjust patch strength at ~once weekly intervals
- Maximum concentration within 12 to 24 hours after first application
|
| Brexpiprazole | 0.5 to 1 | 2 to 4 | 4 | 91 | CYP2D6 and 3A4 to inactive metabolite | - Partial dopamine agonist
- May adjust daily dose by 1 mg increments every ≥4 days
- Variable dose requirements due to CYP2D6 metabolizer phenotype
- Dose adjustment may be needed with CYP2D6 and/or 3A4 inhibitors or inducers*
- Maximum dose 3 mg/day in kidney or hepatic impairment
|
| Cariprazine | 1.5 | 1.5 to 6 | 6 | 48 to 96 (parent) | CYP3A4 to active and inactive metabolites | - Dopamine D3/D2 receptor partial agonist
- May adjust daily dose by 1.5 or 3 mg increments every ≥24 to 48 hours
- Dose adjustment may be needed with CYP3A4 inhibitors or inducers*
- Due to prolonged half-life, changes in dose will not reach steady-state for weeks to months
- Inadequate experience with use in severe kidney or hepatic impairment
|
| Clozapine | 12.5 to 25 | 300 to 600 | 900 | 12 | CYP1A2, 3A4, and other CYPs to primarily inactive metabolites | - Due to its side effect profile (eg, low risk of agranulocytosis, cardiovascular effects, seizures) and strict ANC monitoring requirements, prescribing is typically guided by an experienced provider
- Administration considerations include:
- Orthostatic hypotension and syncope often dose-limiting during titration
- Dose adjustment or avoidance of comedications may be needed due to drug interactions*
- Smoked tobacco decreases clozapine levels; smoking cessation increases levels
- Constipation risk; consider bowel regimen (eg, fiber, fluids, laxative, exercise)
- Interruption of therapy ≥48 hours requires restarting at initial dose
- Other formulations: ODT, oral suspension
- For detailed guidance, including specific titration protocols, refer to separate UpToDate guidelines for prescribing clozapine
|
| Iloperidone | 2 | 12 to 24 | 24 | 18 to 26 | CYP2D6 and 3A4 to active and inactive metabolites | - Daily dose administered in 2 divided doses
- May adjust daily dose by 4 mg every ≥24 hours
- Variable dose requirements due to CYP2D6 metabolizer phenotype
- Dose adjustment may be needed with CYP2D6 and/or 3A4 inhibitors or inducers*
- Orthostatic hypotension is usually the dose-limiting factor in titration
- Interruption of therapy >72 hours requires restarting at initial dose
- Not recommended in severe hepatic impairment
|
| Lumateperone | 42 | 42 (dose is not titrated) | 42 | Approximately 18 after IV administration (IV form is not commercially available) | CYP3A4, other CYPs, and glucuronidation | - Dose adjustment may be needed with CYP3A4 inhibitors*
- Avoid use with CYP3A4 inducers*
- Reduce dose in moderate to severe hepatic impairment
|
| Lurasidone | 40 | 40 to 80 | 160 | 29 to 40 | CYP3A4 to active and inactive metabolites | - May adjust daily dose by 40 mg increments every ≥3 days
- Needs to be taken with a meal (eg, ≥350 calories) to be adequately absorbed
- Lower initial dose (20 mg/day) and maximum dose (40 to 80 mg/day) in kidney or hepatic impairment
|
| Olanzapine | 5 to 10 | 10 to 20 | 30 | 30 to 38 | CYP1A2, CYP2D6 (minor) and glucuronidation | - May adjust daily dose by 5 mg increments every 3 to 7 days
- Smoked tobacco decreases olanzapine levels; smoking cessation increases levels
- Based upon clinical experience, some patients benefit from doses of up to 40 mg/day
- Other formulations: ODT, short-acting IM, LAI
|
| Paliperidone | 6 | 6 to 12 | 12 | 23 | Minimal hepatic metabolism; excreted mainly unchanged in urine | - May adjust daily dose by 3 mg increments every 3 to 5 days
- Dose reduction in kidney impairment
- Other formulation: LAI
|
| Pimavanserin | 34 | 34 (dose is not titrated) | 34 | 57 (parent drug) | CYP3A4 and 3A5 to active metabolite | - Used for treatment of psychosis in Parkinson disease
- Dose adjustment may be needed with 3A4 inhibitors or inducers*
|
| Quetiapine | 50 (immediate release) | 400 to 800 | 800 | Approximately 6 (parent drug) | CYP3A4 and 2D6 (minor) to active and inactive metabolites | - Dose-dependent QTc prolongation
- Daily dose for immediate release administered in 1 to 3 divided doses
- Immediate release: May adjust daily dose by 25 or 50 mg every ≥2 days; increasing to 75 to 100 mg increments if tolerated
- Extended release: May adjust by daily dose 300 mg every ≥1 day
- Orthostatic hypotension and/or sedation often dose limiting in titration
- Reduced dose in mild to moderate hepatic impairment; avoid use in advanced cirrhosis
|
| Risperidone | 1 to 2 | 2 to 6 | 8 | 20 | CYP2D6 and 3A4 to active and inactive metabolites; substrate of P-glycoprotein | - Daily dose administered in 1 or 2 divided doses
- May adjust by increments of 1 or 2 mg every ≥24 hours
- Doses greater than 8 mg/day approved by some regulatory authorities are not recommended
- Dose adjustment may be needed with CYP2D6 inhibitors/inducers or CYP3A4 inducers*
- Reduced dose in moderate to severe kidney or hepatic impairment
- Other formulations: ODT, oral solution, LAI
|
| Ziprasidone | 40 to 80 | 40 to 160 | 160 | 7 | CYP3A4, 1A2 (minor), and other oxidases to inactive metabolites | - Dose-dependent QTc prolongation
- Daily dose administered in 2 divided doses
- May adjust total daily dose by 20 to 40 mg every ≥2 days
- Needs to be taken with a meal (eg, ≥500 calories) to be adequately absorbed
- Other formulation: Short-acting IM
|
