Is Abilify (aripiprazole) safe for use in a pregnant patient with depression?

Is Abilify (Aripiprazole) Safe in Pregnancy for Depression?

Abilify (aripiprazole) is not recommended as a treatment for depression during pregnancy—SSRIs, particularly sertraline, should be used instead as first-line pharmacotherapy when antidepressants are indicated. 1, 2

Why Aripiprazole Is Not Appropriate for Depression in Pregnancy

Indication Mismatch

• Aripiprazole is an atypical antipsychotic approved for schizophrenia and bipolar disorder, not unipolar depression during pregnancy 3
• The evidence-based treatment algorithm for depression in pregnancy prioritizes psychotherapy and SSRIs, not antipsychotics 1

FDA Safety Concerns Specific to Aripiprazole

• Neonates exposed to aripiprazole during the third trimester are at risk for extrapyramidal symptoms and withdrawal symptoms following delivery, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders 3
• These symptoms vary in severity, and some neonates require prolonged hospitalization 3
• Animal studies showed developmental toxicity at doses 10 times the maximum recommended human dose, including fetal death, decreased fetal weight, undescended testicles, skeletal abnormalities, and diaphragmatic hernia 3

Recommended Treatment Algorithm for Depression in Pregnancy

Mild Depression (Recent Onset ≤2 Weeks)

• Begin with monitoring, exercise, and social support before pharmacotherapy 1
• Offer evidence-based psychotherapy (cognitive therapy) if symptoms don't improve within two weeks 1

Moderate-to-Severe Depression or Treatment-Resistant Cases

• Sertraline should be the first-line SSRI due to minimal excretion in breast milk and low infant-to-maternal plasma concentration ratios 2
• Start at 25-50 mg daily and titrate slowly while monitoring the newborn 2
• Continue treatment throughout pregnancy at the lowest effective dose rather than discontinuing, as withdrawal increases relapse risk 2

Special Indications for Antidepressants Over Psychotherapy Alone

• History of severe suicide attempts or severe depression with previous good medication response 4, 1
• Previous relapse when discontinuing antidepressant treatment 1
• Inadequate symptom reduction with psychotherapy alone 1

Safety Profile of SSRIs vs. Aripiprazole

SSRI Safety Data (Particularly Sertraline)

• Recent high-quality evidence provides reassurance that SSRI use during pregnancy does not substantially increase risk of autism spectrum disorder or ADHD—these associations are largely due to confounding factors like maternal psychiatric illness 4, 2
• No increased risk of cardiac malformations with first-trimester sertraline use in large population-based studies 1, 2
• Neonatal adaptation syndrome occurs in approximately 30% of third-trimester SSRI exposures but is self-limiting, resolving within 1-4 weeks 1, 2
• Possible association with persistent pulmonary hypertension of the newborn (PPHN) with number needed to harm of 286-351 1, 2

Risks of Untreated Depression

• Untreated depression carries significant documented risks including premature birth, decreased breastfeeding initiation, increased hospitalization, and suicide risk 1, 3, 5
• Women who discontinue antidepressants during pregnancy show significantly increased relapse risk 3

Critical Clinical Pitfalls to Avoid

• Do not use aripiprazole for unipolar depression in pregnancy—it lacks efficacy data for this indication and carries specific neonatal risks 3
• Do not avoid all pharmacotherapy due to fear of medication risks, as untreated maternal depression poses substantial harm to both mother and infant 1, 2
• Do not discontinue effective SSRI treatment abruptly during pregnancy without psychiatric consultation, as relapse risk is significantly elevated 2, 3
• Avoid paroxetine specifically, which has FDA pregnancy category D classification due to cardiac malformation concerns 1, 2

Monitoring Requirements

• Screen all pregnant women for depression using validated tools (Patient Health Questionnaire, Hospital Anxiety and Depression Scale, or Edinburgh Postnatal Depression Scale) 4, 1
• Arrange early follow-up after hospital discharge for infants exposed to SSRIs 2
• Monitor infants for signs of drug toxicity or withdrawal over the first week of life 2