Second Generation Anti-Psychotics for ICU Use

Note No SGA has an IV formulation. Short-acting IM options: olanzapine (Zyprexa), ziprasidone (Geodon), aripiprazole (Abilify). All antipsychotics carry a boxed warning for ↑ mortality in elderly patients with dementia-related psychosis.

Dosing & Frequency

• Start 12.5–25 mg PO q8–12h; ↑ by 12.5–50 mg/day to effect.
• Typical ICU total: 50–300 mg/day (divide). Often 50–100 mg HS plus small daytime doses.
• Usual max (delirium): 400–600 mg/day; titrate to sedation/orthostasis tolerance.

Onset & PK

• Onset of sedation ~1–2 h; t½ (IR) ~6 h.
• Hepatic metabolism (CYP3A4).

Contraindications/Cautions

• Orthostatic hypotension, somnolence; start low in frail or hepatic impairment.
• Boxed warning in dementia psychosis.

Interactions

• ↑ levels: strong CYP3A4 inhibitors (azoles, clarithromycin, ritonavir).
• ↓ levels: CYP3A4 inducers (carbamazepine, phenytoin, rifampin).

Monitoring

• RASS/oversedation, vitals, falls risk.
• ECG if QT risk/polypharmacy.
• Metabolic panel if >1–2 weeks (glucose, lipids); LFTs if prolonged use.

Tip Helpful for hyperactive/mixed delirium and sleep reversal; relatively low EPS.

Dosing & Frequency

• PO/ODT: 2.5–5 mg q12–24h; ↑ by 2.5–5 mg to 5–20 mg/day.
• IM (short-acting): 5–10 mg once; may repeat ≥2 h; max 30 mg/day.

Onset & PK

• IM onset ~15–45 min; PO ~1–2 h; t½ ~30 h.
• Lower QT effect vs ziprasidone/haloperidol.

Contraindications/Cautions

• Avoid IM within ~1 hour of parenteral benzodiazepines (respiratory/CNS depression).
• Anticholinergic burden; metabolic effects.

Interactions

• Smoking (CYP1A2 induction) ↓ levels; CNS depressants ↑ sedation.

Monitoring

• RASS/oversedation, airway after IM if combined sedatives.
• ECG if risk; metabolic labs if extended use.

Dosing & Frequency

• 0.5–1 mg PO q12h; ↑ by 0.5–1 mg every 12–24 h to 2–4 mg/day.
• Frail/renal/hepatic: consider 0.25–0.5 mg q12h start.

Onset & PK

• Onset 1–2 h; active metabolite t½ ~21 h.
• Renal/hepatic considerations for dose.

Contraindications/Cautions

• Orthostasis; ↑ prolactin/EPS risk; dementia boxed warning.

Interactions

• CYP2D6 inhibitors (fluoxetine, paroxetine) ↑ levels; additive QT agents.

Monitoring

• ECG if QT risk; EPS/AIMS; prolactin symptoms; renal/hepatic function.

Dosing & Frequency

• IM: 10 mg q2h or 20 mg q4h PRN; max 40 mg/day.
• PO: 20–40 mg BID with ≥500 kcal (not ideal in NPO/poor intake).

Contraindications/Cautions

• Contraindicated in known QT prolongation, recent MI, uncompensated HF, or significant arrhythmias. Correct K/Mg first.

Interactions

• Avoid other QT-prolongers (amiodarone, methadone, azithro/fluoroquinolones, ondansetron); caution with diuretics.

Monitoring

• ECG baseline/post-dose if risk; K/Mg; vitals; EPS/NMS surveillance.

Onset & PK

• IM onset ~15–30 min; notable QT liability.

Dosing & Frequency

• IM: 9.75 mg once (range 5.25–15 mg); may repeat q2h; max 30 mg/day.
• PO (delirium off-label): 2–5 mg daily → 5–10 mg/day.

Onset & PK

• IM onset ~1–3 h; very long t½ (~75–95 h including metabolite).
• Lower QT liability; risk of akathisia/activation.

Interactions

• CYP2D6/3A4 inhibitors ↑ levels (fluoxetine, paroxetine, azoles, macrolides); inducers ↓ levels (carbamazepine, rifampin).
• Consider dose adjustments per interaction strength.

Monitoring

• RASS; EPS/akathisia; ECG if risk; sedation vs activation balance.

Dosing & Frequency

• 3–6 mg PO daily (ER).
• Renal adjust: CrCl 50–80 → 3 mg daily (max 6); CrCl 10–50 → 1.5 mg daily (max 3).
• Depot forms are not for acute agitation.

Contraindications/Cautions

• Orthostasis; ↑ prolactin; dose per renal function.

Interactions & Monitoring

• Fewer CYP issues (active metabolite of risperidone); additive QT agents.
• ECG if risk; renal function; EPS/AIMS; prolactin symptoms.

Dosing & Frequency

• 5–10 mg SL q12h. No food/drink for 10 min after dose.

Cautions & Interactions

• Avoid severe hepatic impairment; oral hypoesthesia common.
• CYP1A2/2D6 interactions possible (smoking induction).

Monitoring

• RASS; EPS; ECG if QT risk; hepatic function if concern.

Dosing & Frequency

• 20–40 mg nightly with ≥350 kcal; may ↑ to 80 mg/day.
• Not ideal for rapid ICU control (slower onset).

Interactions & Monitoring

• Strong CYP3A4 inhibitors/inducers significantly alter levels (azoles/clarithro vs rifampin/carbamazepine).
• RASS; EPS; ECG if risk; basic metabolic monitoring if >1–2 weeks.

Cautions

• Akathisia; generally low metabolic/QT profile.

Dosing & Role

• Start 12.5 mg once–BID; ↑ by 25–50 mg/day. Not for acute ICU agitation initiation.

Major Safety

• REMS/ANC required; agranulocytosis, myocarditis, seizures, ileus, sialorrhea, orthostasis.

Interactions & Monitoring

• Multiple CYPs (1A2, 3A4, 2D6); smoking ↓ levels.
• ANC per program; ECG if risk; troponin/CRP early; bowel regimen/watch ileus.

Use case Continue home therapy if already established; avoid de-novo starts for agitation in ICU.

Dosing & Frequency

• Titration needed due to orthostasis: Day 1 1 mg BID → over several days to 6–12 mg BID.
• Not suited for rapid agitation control.

Cautions & Monitoring

• Orthostatic hypotension; moderate QT risk → ECG if risk.
• EPS checks.

Interactions

• CYP2D6/3A4 inhibitors ↑ levels; avoid additive QT agents.

Dosing & Frequency

• 0.5–1 mg daily; titrate to 2–3 mg/day; slower onset (maintenance role).

Interactions & Monitoring

• CYP2D6/3A4 inhibitors ↑ levels; inducers ↓ levels.
• RASS; EPS/akathisia; ECG if risk.

Notes

• Long t½ (~91 h); not ideal for fast titration.

Dosing & Frequency

• 1.5 mg daily → may ↑ to 3 mg; very long effective t½ (active metabolite up to weeks).

Cautions & Interactions

• Akathisia/insomnia; avoid for rapid control needs.
• Strong CYP3A4 inhibitors/inducers significantly alter levels.

Monitoring

• RASS; EPS; ECG if risk; watch for activation.

Dosing & Frequency

• 42 mg PO daily; not for acute agitation (slower onset).

Cautions & Interactions

• Somnolence; relatively low metabolic/QT profile; limited ICU data.
• Strong CYP3A4 inhibitors/inducers—avoid/adjust per label.

Monitoring

• RASS; EPS; ECG if risk; consider metabolic labs if extended use.

Safety Reconcile sedatives, opioids, and QT-prolonging drugs; correct K/Mg/Ca before agents with QT liability. No IV SGAs exist; short-acting IMs shown above are options for rapid control when appropriate.