| D2 & 5-HT2A antagonist | Asenapine | Saphris® | 10–20 mg/day SL | Yes (≥10 yrs) | Schizophrenia, Bipolar | Moderate | Low | Moderate | Moderate | Oral numbness, must take sublingually | No | Caution in severe hepatic impairment | Hepatic, EPS, sedation | Use with caution—greater sensitivity to hypotension | Limited data; avoid unless benefits outweigh risks | Likely safe, limited data | CYP1A2 inhibitors/inducers, QT-prolonging agents | Onset: ~1 wk; Half-life: 24 hrs | Not routinely monitored |
| D2 & 5-HT2A antagonist | Iloperidone | Fanapt® | 12–24 mg/day | No | Schizophrenia | Moderate | Moderate | Moderate | High | Orthostatic hypotension, titration required | No | Hepatic (caution); avoid in renal impairment | BP, ECG (QTc), weight | Start low, go slow due to hypotension risk | Not recommended in pregnancy | Unknown, caution advised | CYP2D6 & 3A4 inhibitors, QT-prolonging agents | Onset: 1–2 wks; Half-life: 18 hrs | Not routinely monitored |
| D2 & 5-HT2A antagonist | Lurasidone | Latuda® | 40–160 mg/day | Yes (≥13 yrs) | Schizophrenia, Bipolar Depression | Low | Low | Moderate | Minimal | Akathisia, must take with food | No | Renal/hepatic (dose adjustments needed) | Renal, hepatic function, glucose | Safer choice in elderly due to metabolic profile | Category B, may be used if clinically needed | Likely safe | Strong CYP3A4 inducers/inhibitors; avoid with ketoconazole | Onset: 1–2 wks; Half-life: 18 hrs | Not routinely monitored |
| D2 & 5-HT2A antagonist | Olanzapine | Zyprexa® | 10–20 mg/day | Yes (≥13 yrs) | Schizophrenia, Bipolar I | High | High | Low | Moderate | Metabolic syndrome, sedation | Yes (Zyprexa Relprevv) | Hepatic (reduce dose in impairment) | Lipids, glucose, weight, LFTs | Avoid in dementia-related psychosis due to mortality risk | Avoid in pregnancy; associated with neonatal effects | Compatible with monitoring | CYP1A2 inhibitors/inducers, benzodiazepines (enhanced sedation) | Onset: few days–2 wks; Half-life: 30 hrs | Not routinely monitored |
| D2 & 5-HT2A antagonist | Paliperidone | Invega® | 3–12 mg/day | Yes (≥12 yrs) | Schizophrenia, Schizoaffective | Low | Moderate | High | Moderate | Hyperprolactinemia, renal dose needed | Yes (Invega Sustenna/Trinza/Hafyera) | Renal (adjust), not hepatic metabolized | Renal function, EPS, prolactin | Safer option due to renal clearance profile | Avoid unless benefits outweigh risks | Unknown; likely low transfer | QT-prolonging drugs, dopaminergic antagonists | Onset: ~1 day; Half-life: 23 hrs (oral), 25–49 days (LAI) | Not routinely monitored |
| D2 & 5-HT2A antagonist | Quetiapine | Seroquel® | 300–800 mg/day | Yes (≥10 yrs) | Schizophrenia, Bipolar, Depression (XR) | High | Moderate-High | Low | Low | Orthostatic hypotension, sedation | No | Hepatic (start low) | Lipids, glucose, weight, BP, LFTs | High sedation risk in elderly, start low | Use only if clearly needed, may cause withdrawal in neonates | Present in breast milk; monitor infant | CYP3A4 inhibitors/inducers, CNS depressants, anticholinergics | Onset: few days; Half-life: 6 hrs | Not routinely monitored |
| D2 & 5-HT2A antagonist | Risperidone | Risperdal® | 2–6 mg/day | Yes (≥5 yrs) | Schizophrenia, Bipolar, Autism-related irritability | Moderate | Moderate | High | Low | EPS, hyperprolactinemia | Yes (Consta, Perseris) | Renal & hepatic (adjust dose) | Prolactin, EPS, weight, glucose | Lower doses preferred, risk of orthostatic hypotension | Avoid in pregnancy unless necessary | Present in milk; monitor infant for sedation | CYP2D6 inhibitors, antihypertensives, dopaminergic agents | Onset: few days–2 wks; Half-life: 20 hrs (oral), 3–6 days (LAI) | Not routinely monitored |
| D2 & 5-HT2A antagonist; inhibits 5-HT & NE reuptake | Ziprasidone | Geodon® | 80–160 mg/day | Yes (≥10 yrs) | Schizophrenia, Bipolar | Low | Low | Moderate | High | QT prolongation, take with food | No | Caution in hepatic impairment | ECG (QTc), electrolytes | Avoid in elderly with cardiac issues | Avoid during pregnancy due to QT risk | Not recommended due to QT risk | QT-prolonging agents, CYP3A4 inhibitors | Onset: 1–2 wks; Half-life: 7 hrs | Not routinely monitored |
| D4 > D2 antagonist; 5-HT2A, H1, α1 blocker | Clozapine | Clozaril® | 300–900 mg/day | Yes (≥10 yrs) | TR Schizophrenia, suicidality | High | High | Low | Mild | Agranulocytosis, myocarditis, seizures | No | Hepatic (monitor), renal (monitor) | CBC (weekly to q4w), ECG, troponin, weight | Not first-line in elderly; high risk of sedation/seizure | Avoid unless life-saving | Avoid due to risk of agranulocytosis | Carbamazepine (↓ levels, ↑ toxicity), benzodiazepines, CYP1A2/3A4 interactions | Onset: 1–3 wks; Half-life: ~12 hrs | 350–600 ng/mL (monitor weekly initially) |
| Partial D2 & 5-HT1A agonist; 5-HT2A antagonist | Brexpiprazole | Rexulti® | 1–4 mg/day | No | MDD adjunct, Schizophrenia | Low | Low | Low | Minimal | Mild weight gain, akathisia | No | Hepatic (adjust), Renal (adjust) | Glucose, weight, agitation | Safer profile for elderly | Limited data; avoid unless necessary | Likely safe with monitoring | CYP3A4 & 2D6 inhibitors/inducers | Onset: 1–2 wks; Half-life: 91 hrs | Not routinely monitored |
| Partial D2 agonist, 5-HT1A agonist; 5-HT2A antagonist | Aripiprazole | Abilify® | 10–30 mg/day | Yes (≥6 yrs) | Schizophrenia, Bipolar, MDD adjunct | Low | Low | Moderate | Minimal | Akathisia, agitation | Yes (Maintena, Aristada) | Adjust in hepatic impairment | EPS, agitation, glucose | Lower dose preferred; may worsen impulsivity | May be used with caution; limited fetal risk | Low levels in milk; generally safe | CYP3A4 & 2D6 inhibitors, SSRIs, CNS depressants | Onset: few days–2 wks; Half-life: 75 hrs (oral), 30–47 days (LAI) | Not routinely monitored |
| Partial D3 > D2 agonist; 5-HT2A antagonist | Cariprazine | Vraylar® | 1.5–6 mg/day | No | Schizophrenia, Bipolar I | Low | Low | Moderate | Minimal | Akathisia, insomnia | No | Hepatic (mild/mod OK), not for severe | Mental status, EPS, glucose | Limited data in elderly, use caution | Avoid unless benefits outweigh risks | Unknown; use caution | CYP3A4 interactions (inhibitors/inducers), avoid with strong inhibitors | Onset: slow (up to 3 wks); Half-life: 2–4 days (parent), 1–3 wks (active metabolites) | Not routinely monitored |
