Table 5.

First-Line Agents for Acute Manic or Mixed Episode^a

Class	Agent	Target Dose	Notable Adverse Effects	Notes
Mood stabilizers	Lithiumb	Sufficient for blood level of 0.6–1.2 mEq/L, usual dose 900–1,800 mg	Sedation, dry mouth, polyuria; more rarely kidney or thyroid failure	May be slower to control mania than other options
	Divalproex	Titrate rapidly to a blood level of 85–125 μg/mL; up to 60 mg/kg	Sedation, nausea, weight gain; may cause menstrual irregularities; rare pancreatitis or liver failure	Very high risk of neural tube defects with fetal exposure; caution in women of childbearing age
Second-generation antipsychotics	Aripiprazole	15–30 mg/d	Akathisia and other EPS, sedation	Among the least likely second-generation antipsychotics to cause weight gain
	Asenapine	10 mg bid	EPS, sedation	…
	Olanzapinec	15–20 mg/d	Sedation, weight gain, less commonly EPS	Weight gain; lipid and glucose derangements may be particularly severe
	Quetiapineb	400–800 mg/d	Sedation, weight gain, less commonly EPS	Titrate immediate-release form over 6 days
	Risperidone	3–6 mg/d	EPS, sedation, hyperprolactinemia	…
	Ziprasidone	40–80 bid	EPS, sedation or agitation	Taken with meals to improve absorption; contraindicated if history of prolonged QTc interval or in combination with QTc-prolonging medications

^aBased on Suppes et al,⁸ Malhi et al,¹⁷ Yatham et al,²⁹ Goodwin,³⁰ and Stoner and Dahmen.³²

^bNot recommended as first-line for mixed episodes.

^cOlanzapine is not generally recommended as first-line due to metabolic adverse effects.

Abbreviation: EPS = extrapyramidal symptoms.

Symbol: … = no data.