# 27 - F. Atypical antipsychotics

# F. Atypical antipsychotics:

© SPMM Course 
F. Atypical antipsychotics: 
All atypicals are orally well absorbed. 
Drug 
Half life 
Chlorpromazine equivalents 
(100mg/day CPZ or 2mg Haloperidol) 
Risperidone 
15hrs 
2 mg/day 
Clozapine 
16hrs 
50 mg/day 
Quetiapine 
6hrs 
75 mg/day 
Olanzapine 
30 hrs 
5mg/day 
Aripiprazole 
90hrs 
7.5 mg/day 
From Woods SW. J Clin Psychiatry. 2003 Jun;64(6):663-7. 
 Risperidone undergoes extensive first-pass hepatic metabolism to 9-hydroxyrisperidone, an active 
metabolite. CYP 2D6 catalyzes hydroxylation of risperidone to 9-hydroxyrisperidone. Risperidone is 
90% protein bound; its metabolite is 77% bound. 
 Paliperidone is the major active metabolite of risperidone (9-OH). It is a potent 5HT2 blocker apart 
from partially blocking D2 receptors. Its efficacy and side effects are the same as risperidone. It comes 
in a sustained release preparation similar to methylphenidate XL wherein gradual water absorption 
delivers the drug molecules slowly. Once daily administration is sufficient; there is no need to titrate 
the dose. 
 Quetiapine has a shorter half-life of 6 to 12 hours, and multiple daily dosing is required; though with 
longer use, as pharmacodynamic receptor action has longer duration once daily dosing may be 
sufficient. 
 Aripiprazole and its active metabolite dihydro 
aripiprazole have exceptionally long half-lives of 75 
(nearly 3 days) and 94 hours respectively, and steady 
state concentrations are achieved after 14 days. 
Aripiprazole is metabolized by CYP 3A4 and CYP 
2D6 enzymes. It is highly (99%) protein bound. 
 Atypical depots 
o Aripiprazole depot: no need to refrigerate; once 
monthly; gluteal administration only; only 2 
weeks oral dose tapering needed. 
o Paliperidone depot does not need oral tapering; 
once monthly; no need to refrigerate; primarily 
renal excretion. 
o Risperidone microspheres are used in depot 
preparations; they release the active drug at 
therapeutic levels only 3 weeks after gluteal or 
deltoid injection. Long-acting risperidone should 
DEPOT KINETICS 
 
Some long-acting injections (such as 
risperidone, pipotiazine) show delayed as 
well as prolonged release. These require 
adeqaute cover with oral antipsychotics after 
first dose is administered. 
 
Steady-state plasma levels are often delayed 
for 2–3 months. During this time, plasma 
levels are likely to rise substantially even 
when dosages are not increased, thus 
producing dose-dependent side effects. 
 
Dose–response relationships are not clearly 
understood for most LAIs. Test doses are 
often used but may not be sufficient to assess 
tolerability in longer-term use.