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Original Research Focus on Women’s Mental Health November 5, 2025

Targeting Intolerance of Uncertainty During Pregnancy: A Randomized Controlled Trial to Prevent Postpartum Anxiety Disorders

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J Clin Psychiatry 2026;87(1):25m15979

Abstract

Objective: Postpartum anxiety is common, often underrecognized, and associated with numerous negative outcomes for both the perinatal individual and their infant. Despite its high prevalence and burden, research focused on preventative strategies for postpartum anxiety remains very limited. This study investigated whether a 6-week cognitive behavioral therapy protocol targeting intolerance of uncertainty (CBT-IU) during pregnancy could reduce risk for postpartum anxiety disorders among individuals with heightened intolerance of uncertainty (IU).

Methods: In this investigator-initiated, single-site, proof-of-concept, randomized controlled trial (RCT), eligible participants (n=37), between 14 and 32 weeks’             gestation, with heightened IU (baseline score of ≥64 on the 27-item Intolerance of Uncertainty Scale) were randomized to a 6-session individual CBT-IU or care as usual (CAU), of whom 35 completed measures and were included in analyses. The primary objective of this study was to evaluate whether CBT-IU for pregnant individuals with elevated IU could reduce the risk of postpartum anxiety disorder compared to CAU. Secondary outcomes included changes in worry, depression, and emotion regulation.

Results: CBT-IU significantly reduced the risk of postpartum anxiety disorder onset compared to CAU (P<.001), with none of the participants in the CBT-IU group meeting diagnostic (or provisional) criteria for an anxiety or related disorder, compared to 31.6% of participants in the CAU group. CBT-IU participants showed clinically significantly reductions in IU (P=.003), worry symptoms (P<.001), emotion dysregulation (P=.018), and interviewer-rated anxiety symptoms (P<.001) compared to CAU. Treatment satisfaction among CBT-IU participants was high.

Conclusion: These findings suggest that targeting IU during pregnancy may be an effective preventive strategy for reducing the risk of postpartum anxiety disorder onset. This proof-of-concept RCT supports a large-scale RCT to ultimately test CBT-IU as an effective intervention for prevention of postpartum anxiety disorders.

Trial Registration: ClinicalTrials.gov identifier: NCT05691140.
J Clin Psychiatry 2026;87(1):25m15979
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