DRUG OF THE DAY:
QUETIAPINE (SEROQUEL)
FDA-APPROVED INDICATIONS:
Acute schizophrenia, schizophrenia maintenance, acute mania (monotherapy and adjunct to lithium or
valproate), bipolar maintenance, bipolar depression, depression
MECHANISM OF ACTION/PHARMACOKINETICS:
• Primarily 5HT2A + D2 antagonist
• Blocks D2-R (↓pos sxs & stabilizes affective sxs)
• Blocks 5HT2A-R (↑dopamine release in some areas → ↓motor SEs + improved cog/affect sxs)
• 5HT1A partial agonist, NE reuptake blockage, 5HT2C & 5HT7 antagonist → antidepressant effects
• 5HT1A helps cognitive and affective sxs
• H1 antagonist → enhanced sleep (also M1 and α1 antagonism)
• Half-life 6-7 hrs, CYP450 3A4
DOSING:
• (Schizophrenia) start 25 mg/day BID; ↑25-50 mg BID daily until desired effect, max 800 mg/day
• (Acute bipolar mania, initiate BID dosing)
o 100 mg total on Day 1
o Increase to 400 mg/day by Day 4
o Further adjustment to 800 mg/day by Day 6
o Increments of no greater than 200 mg/day
• (Bipolar depression) once daily QHS; titrate as needed to reach 300 mg/day by Day 4
SIDE EFFECT PROFILE:
• H1: sedation and poss. wt gain
• α1: dizziness, sedation, orthostatic hypotension
• M1: xerostomia, constipation, sedation
• D2: motor side effects (rarely)
MONITORING:
• BMI monthly q3months, then quarterly
• Fasting lipids qmonthly several months if high risk met syndrome
• BP, FBG, lipids within 3 months then annually
• Treat or switch if pt becomes overweight, obese, pre-diabetic, diabetic, HTN, dyslipidemic
PEARLS:
• Avoid use with drugs that ↑QT interval or in pts w/ risk factors for ↑QT interval
• Active metabolite, norquetiapine, causes NE reuptake inhibition and antagonizes 5HT2C (mood
and cognition benefits)
• Preferable to anticonvulsant mood stabilizers if tx required during pregnancy
o Risk of abnl mvmts & w/d sxs in newborns of mothers taking med in 3rd trimester
• Essentially no motor SEs or PRL elevation
• May be preferred anti-Ψotic for Ψosis in Parkinson’s dz & LB dementia
• Suspend treatment if ANC falls below 1,000/mm3 (low risk of quetiapine-induced neutropenia)
Stahl’s Essential Psychopharmacology, 4th Ed
At antipsychotic doses (i.e. up to 800 mg/day), quetiapine has a relatively wide binding profile, with actions at multiple
serotonergic, muscarinic, and α-adrenergic receptors, H1 receptr blockade is also present. At antidepressant doses (i.e. approx.
300 mg/day), the binding profile of quetiapine is more selective and consists primarily of actions at D 2, 5HT2A, 5HT2C, and 5HT1A
receptors as well as inhibition of the NE transporter. At sedative-hypnotic doses (i.e. 50 mg/day), the most prominent
pharmacological property of quetiapine is H1 an tagonism.
Stahl’s Essential Psychopharmacology Prescriber’s Guide, 6 th Ed