AstraZeneca; patent expires 2011
Bipolar mania, as monotherapy or with lithium or Depakote.
Common off-label use in a variety of mood, anxiety, and personality disorders.
D2 and 5HT 2 receptor antagonist
Supplied in 25 mg, 100 mg, 200 mg, 300 mg, and 400 mg tablets.
Start at 25-50 mg BID or TID, increasing to 300-400 mg/day (BID or TID) by day 4.
Optimal titration strategy is controversial. Early sedation may be unrelated to initial dose and may disappear by week two regardless of dose. Consensus now is that target dose should be 400 mg to 800 mg/day.
In off-label use in personality disorders, anxiety, and insomnia, dosing often stabilizes at the 25 mg BID-QID range.
A slower rate of titration and lower target dose may be needed in elderly patients and patients with hepatic impairment; no dosage adjustment necessary for renal insufficiency.
BLACK BOX WARNING: All atypicals may increase mortality in elderly patients by 1.7 times greater than placebo.
Most common are somnolence, hypotension, dry mouth, dizziness, constipation.
EPS: Virtually non-existent, even at high doses.
Weight gain: Moderate, less than Zyprexa, more than Geodon or Abilify.
Glucose/Lipids: May lead to new-onset diabetes and exacerbation of pre-existing problems; can cause significant elevation of triglycerides.
EKG: No concerns.
Prolactin level: No elevation.
Cataracts occurred in dogs given 4 times the maximum recommended dose, but post-marketing surveillance has revealed only very rare cases of lens abnormalities; .
Transient bumps in liver function tests possible, but normalize with continued treatment.
Pregnancy Category C.
Does not inhibit liver enzymes, so it does not affect metabolism of other drugs.
Metabolized by CYP3A4; drugs that affect this pathway will affect clearance:
Tegretol, Dilantin, and Mellaril lower Seroquel levels.
Erythromycin and ketoconazole increase Seroquel levels.
6 hour half-life