| Drug | CPE (mg) | OLE in Schizophrenia (mg) | Monograph Doses for Psychosis | Bioavailability | Protein Binding | Peak Plasma Level (h) (Tmax) | Elimination Half-Life (h) | Metabolizing Enzymes/Transporters (CYP450; other) | Enzyme Inhibition/Transporters (CYP450; other) | % D2 Receptor Occupancy (dose & plasma level) | % 5-HT2A Occupancy (dose) |
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Iloperidone (Fanapt) |
N/A | ? | Oral: 1mg bid to start and increase daily for 7 days to a target dose of 6mg bid |
96% |
∼95% | 2–4 |
18–33 (parent) 26(K)–37(D) and 23(K)–31(D) (active metabolites) |
2D6, 3A4(3) | – | ||
| Paliperidone (active metabolite of risperidone; Invega) | ? |
Oral: 6mg od (preferably in AM) If needed, increase by 3mg q 5 days to a maximum of 12mg/day |
28% | 74% (to albumin and α1-AGP) | 24 |
23 In mild, moderate, and severe renal impairment: 24, 40, and 51, respectively |
2D6, 3A4(w), P-gp (Minimally metabolized, <7%) |
P-gp(w) (at high doses in vitro) |
66% (6mg) 70−80% predicted for 4.5−9mg |
? | |
| Risperdal M-tab) | 2–2.5 | 6.0 |
Oral: 1–2 mg od–bid and increase by 0.5–2 mg q 1–7 days Usual daily dose: 4–6 mg Doses above 12 mg/day do not usually produce further improvement Maximum: 16mg/day |
70% |
88–90% (parent; to albumin and α1-AGP) 77% (active metabolite) Reduced in hepatic disease |
1–1.5 (parent) 3(K)–17(D) (active metabolite) |
3(K)–20(D) (parent) 21(K)–30(D) (active metabolite) Increased by ∼60% in moderate to severe renal disease |
2D6(p), 3A4, P-gp | 2D6, 3A4(w) |
60–75% (2–4 mg) 63–85% (2–6 mg; 36–252 nmol/l) |
60–90% (1–4 mg) |
| Benzoisothiasol | |||||||||||
| Lurasidone (Latuda(B)) | ? | ? | Oral: 40 mg od to start Maximum: 80mg od Doses > 80mg/day do not appear to provide additional benefit | 9−19% | >99.8% (to albumin and α1-AGP) | 1−3 | 18−37 (parent) 7.5−10 (active metabolite) | 3A4(p) | – | 63−79% (40−80mg) | ? |
| Benzothiazolylpiperazine | |||||||||||
|
(Geodon(B), Zeldox) |
40–80 | 160 |
Oral: 20–40 mg bid to start. If needed, increase ≥ q 2 days. Doses >80 mg bid generally not recommended. Short-term efficacy data for 100mg bid but limited safety data |
Oral: 30% (60% with food) | >99% (to albumin and α1-AGP) | Oral: 6–8 (Cmax increased 32–72% in mild renal impairment) |
Oral: 4–10 dose-dependent (6.6 mean) No change in the elderly or renal disease Prolonged in hepatic disease (mean in hepatic disease = 7.1 vs. 4.8 in control group) |
3A4(m), 1A2(w), 2D6, 3C18/19; Aldehyde oxydase(w) |
2D6(w), 3A4(w) |
45–75% (40–80 mg) |
80–90% (40–80 mg) |
| Ziprasidone mesylate | Short-acting IM: 10 mg q 2 h or 20 mg q 4 h to a maximum of 40 mg/24 h for up to 3 days | Short-acting IM: 100% | Short-acting IM: ∼60min |
Short-acting IM: 2–5 h (Caution in renal disease due to excipient – cyclodextrin) |
|||||||
| Dibenzodiazepine | |||||||||||
| Clozaril, FazaClo ODT(B)) |
200–250? (CPE unclear) |
400 |
Oral: 12.5mg od or bid to start; increase gradually by 25–50 mg/day increments up to 300–450 mg/day in divided doses by the
end of 2 weeks; subsequent increases ≤ once or twice/week in increments ≤100mg/day Usual range: 300–600mg/day Maximum: 900 mg/day Prescribing restrictions: see “Second-Generation” Antipsychotics/SGAs |
90–95% (40–60% after 1st pass metabolism) | 95–97% (to α1-AGP) | 1–6 (mean 2.5) |
6–33 (mean 12; parent) 11–105 (active metabolite) Caution in the elderly Reduced in smokers (20–40% shorter) |
1A2(p), 2D6(w), 3A4(m), 2C9(w), 2C19(m), 2E1(w); FMO; UGT1A4; P-gp(w) |
1A2(w), 2D6(w), 3A4, 2C9(w), 2C19, 2E1(w) |
38–68% (300–900 mg; 600–2500 nmol/l)(F) |
85–94% (> 125 mg) |
| Dibenzo-oxepinopyrrole | |||||||||||
|
Asenapine (Saphris(B)) |
Oral: 5mg sublingually bid – starting and target dose Maximum: 10mg bid |
35% (<2% if swallowed; reduced if food/drink taken within 10min) |
95% (including albumin and α1-AGP) | 0.5–1 | 24 | 1A2(p), 2D6(w), 3A4(w); UGT1A4(p) | 2D6(w) | 79% (4.8 mg sublingual) | |||
| Dibenzothiazepine | |||||||||||
| Seroquel) |
300–400? (CPE unclear) |
750 |
Oral: 25 mg bid to start; increase by 25–50 mg bid per day, as tolerated, to a target dose of 300 mg/day (given bid) within
4–7 days. Further increases ≥2 days. Usual daily dose: 300–600 mg/day, in divided doses Maximum: 800 mg/day |
∼73% (relative bioavailability; absolute unknown) | 83% | Oral: 0.5–3 |
∼6–7 (parent) ∼12 (active metabolite) Prolonged in hepatic disease (45% longer; based on a low-, single-dose study in those with mild disease), renal disease (25% longer; based on a low-, single-dose study in those with severe disease), and the elderly (30–50% longer) |
3A4(p), 2D6(w); P-gp | 1A2(w), 2D6(w), 3A4(w), 2C9(w), 2C19(w) |
20–44% (300–700 mg) 13–41% (150–750 mg) |
21–80% (150–600 mg) 38–74% (150–750 mg) |
| (Seroquel XR) |
Oral (XR): 150–300 mg od in the evening on day 1, 300–450 mg/day on day 2, then increase by 50mg/day to 800 mg/day if needed Maintenance: 400–800mg/day Maximum: 800 mg/day |
Oral (XR): ∼6 | |||||||||
| Thienobenzodiazepine | |||||||||||
|
Zyprexa, Zyprexa Zydis) |
7.5–10 | 20 |
Oral: 5–10 mg od to start Further dose increases of ≤ 5mg/day at intervals of ≥ 1 week Maximum: 20 mg/day (higher doses, e.g., 40mg/day, have safety but not efficacy data) |
Oral: 57–80% | 93% (to albumin and α1-AGP) | Oral: 5–8 |
21–54 (30 mean) No change in hepatic disease (only based on single-dose study) or renal disease. Prolonged in the elderly (1.5 times longer) and females (30% longer – clinical significance unclear) Reduced in smokers (40% shorter) |
1A2(p), 2D6(w); FMO; UGT1A4(p) |
1A2(w), 2D6(w), 3A4(w), 2C9(w), 2C19(w) |
55–80% (5–20 mg; 59–187 nmol/l) 83–88% (30–40 mg) |
80–90% (5–20 mg) |
| (Zyprexa IntraMuscular) |
Short-acting IM: 10 mg to start (2.5–5 mg in the elderly) If needed, give 2nd dose of 5–10mg 2h after 1st; if 3rd dose needed, give ≥4h after 2nd dose Maximum: 30 mg/day (high rate of orthostatic hypotension) with no more than 3 injections in 24 h |
Short-acting IM: 15–45 min (Cmax 4−5 fold > same oral dose) |