Table 2.

Pharmacotherapeutic options for treating acute depressive episodes

Drug class/name	Regulatory approvala,b	Pregnancy-safety rating (US)c	Summary of major reproductive safety concerns
Mood stabilizers
Lithium	–	D	• Overall MCM rate 2.8% (prospective studies)
			• Includes low risk of Ebstein’s anomaly (one case per 1,000–2,000 births)
			• Reported cases of neonatal adaptation syndrome; risk may be higher with higher maternal lithium levels
			• Reported cases of other neonatal complications
Valproate	–	D	• Highest MCM rates among all mood stabilizers (5%–11%, based on registry study data); risk may be dose-dependent (maternal daily dose)
			• Increased MCM risk when combined with other anticonvulsants
			• Increased risk of adverse neurodevelopmental outcomes
			• Reported cases of neonatal toxicity syndromes
Carbamazepine	–	D	• Overall MCM rate 2%–6% based on registry study data
			• Several adverse neonatal events aside from birth defects reported
Lamotrigine	–	C	• Unclear if lamotrigine increases risk of MCMs above background rates
			• Unclear if lamotrigine increases risk of other neonatal adverse events outside of birth defects
			• No evidence of increased risk of adverse neurodevelopmental outcomes
Antipsychotics, atypical
Olanzapine	Adultsd	C	• MCM risk unclear, very few large-scale studies
			• Very limited data on reproductive risks associated with individual drugs
			• FDA safety warning regarding risk of abnormal muscle movements and withdrawal symptoms in neonates
			• Possible risks of excessive weight gain and gestational diabetes require additional study
Quetiapine	Adultsmono	C	• MCM risk unclear, very few large-scale studies
			• Very limited data on reproductive risks associated with individual drugs
			• FDA safety warning regarding risk of abnormal muscle movements and withdrawal symptoms in neonates
			• Possible risks of excessive weight gain and gestational diabetes require additional study
Lurasidone	Adultsmono,com	B	• No evidence of teratogenicity in animals; no reproductive safety data in humans
			• Available only relatively short time for clinical use

Notes:

^*FDA approval for acute mixed episodes in addition to manic episodes; ^monoapproval as a monotherapy; ^comapproval as combination therapy with lithium or valproate

^aregulatory approval in the US

^bno psychotropic medications (including those used to treat bipolar disorder in any of its phases) are approved for use in the context of pregnancy in the US; information on regulatory approval in the US is for general treatment of bipolar disorder in adults, or in children or youth where specified

^cFDA pregnancy-safety categories are generally defined as: A = adequate, well-controlled human studies fail to show risk to fetus; B = animal studies fail to show risk to fetus, but no adequate, well-controlled studies in humans; C = animal studies show evidence of adverse fetal effects, but no adequate studies in humans – benefits of use in pregnancy may still outweigh risks; D = investigational or postmarketing studies in humans show evidence of adverse fetal effects, but benefits of use in pregnancy may still outweigh risks; E = contraindicated in pregnancy

^dcombination of olanzapine and fluoxetine for treating acute depressive episodes in adults with bipolar I disorder.

Abbreviations: MCMs, major congenital malformations; FDA, US Food and Drug Administration.