Abstract
IMPORTANCE: Antipsychotics are increasingly used in the perinatal period. However, evidence of their effectiveness in the perinatal population is limited. OBJECTIVES: To examine the risk of severe psychiatric relapse during the perinatal period associated with discontinuation of antipsychotic treatment before or during pregnancy in women with primary psychotic disorders or bipolar disorder. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used linked Danish and Swedish national birth registers to identify pregnancies leading to singleton live births from 1998 to 2022 in Denmark and from 2007 to 2017 in Sweden. Women diagnosed with psychotic disorders or bipolar disorder, with a gestational age between 154 and 315 days, and 2 or more antipsychotic prescriptions filled within 1 year before pregnancy were included. Data were analyzed from August 2024 to October 2025. EXPOSURE: The exposure of interest was antipsychotic discontinuation. Discontinuation was defined as no prescription refill within the expected prescription duration plus a 60-day grace period. Women were classified into groups: prepregnancy discontinuation, pregnancy discontinuation, and continuation. The prepregnancy discontinuation group was matched 1:1 to the continuation group, and the pregnancy discontinuation group was separately matched 1:1 to the same continuation group. MAIN OUTCOMES AND MEASURES: The outcome of interest was severe psychiatric relapse in the perinatal period. Hazard ratios (HRs) were estimated for psychiatric relapse, defined as inpatient treatment for psychiatric disorders during pregnancy and up to 3 months post partum, using a stratified Cox proportional hazards regression model. RESULTS: A total of 2000 women with primary psychotic disorders (1265 from Denmark and 735 from Sweden) and 1292 women with bipolar disorder (341 from Denmark and 951 from Sweden) were included. The mean (SD) age was 30.8 (6.0) years for women with psychotic disorders and 29.1 (7.7) years for women with bipolar disorder. For women with psychotic disorders discontinuing antipsychotics before pregnancy, the adjusted HR (AHR) of psychiatric relapse was 1.24 (95% CI, 0.82-1.90) compared with continuation. Pregnancy discontinuation had a higher point estimate for relapse risk (328 pairs; AHR, 1.60 [95% CI, 1.01-2.54]) compared with continuation of antipsychotics. Among women with bipolar disorder, prepregnancy discontinuation (102 pairs; AHR, 0.50 [95% CI, 0.22-1.11]) and pregnancy discontinuation (92 pairs; AHR, 1.00 [95% CI, 0.48-2.10]) point estimates did not show an increased risk of severe relapse, but statistical power was limited. CONCLUSIONS AND RELEVANCE: In this cohort study, women with psychotic disorders who discontinued antipsychotic treatment during pregnancy were at a higher risk of severe relapse and the results for those who discontinued prepregnancy suggest a possible increase in risk, compared with those who continued, which aligns with findings observed beyond the perinatal period; results in women with bipolar disorder were inconclusive. There is an urgent need to investigate the effectiveness of antipsychotics on both severe and nonsevere relapses in the perinatal period in prospective clinical cohort studies.