Metoclopramide Use in Nausea and Vomiting of Pregnancy and Risk of Depressive Symptoms as an Adverse Drug Reaction in the Netherlands: a Disproportionality Analysis in a National Spontaneous Reporting Database

J Acad Consult Liaison Psychiatry. 2026 Mar 7:S2667-2960(26)00027-3. doi: 10.1016/j.jaclp.2026.03.001. Online ahead of print.

ABSTRACT

INTRODUCTION: Metoclopramide is widely used for nausea and vomiting of pregnancy and hyperemesis gravidarum. While it is known to cause depressive symptoms as an adverse drug reaction (ADR), it is unclear if pregnancy increases this risk. This study aims to assess whether metoclopramide-induced depressive symptoms are more common in pregnant women compared to non-pregnant women.

METHODS: A disproportionality analysis was performed using the national spontaneous ADR reporting system of the Netherlands. All reports of ADRs associated with metoclopramide concerning women aged 15-50 years were included. Based on MedDRA-coded terms and case narratives, pregnancy status was determined. Cases were defined as reports on depressive symptoms. A case review was performed. Disproportionality in reporting between pregnant- and non-pregnant women was evaluated using a reporting odds ratio (ROR) with 95% confidence interval (95% CI). For comparison, two other anti-emetic drugs (ondansetron and meclozine with pyridoxine) were also assessed.

RESULTS: Reports of depressive symptoms associated with metoclopramide use were reported more often in pregnant women (21.1%) than in non-pregnant women (3.0%) (ROR 8.6; 95% CI 3.2-23.2). In pregnancy-related cases, depressive symptoms were reported more often following metoclopramide exposure (21.1%) compared to exposure to other anti-emetics (7.3%) (ROR 3.4; 95% CI 1.2-9.3). In 33.3% of the pregnancy-related cases, suicidality tendency was reported. Depressive symptoms were often accompanied by other mood related symptoms including anxiety, panic attacks, agitation and restlessness.

CONCLUSION: Although a causal relationship cannot be established, metoclopramide exposure during pregnancy was associated with increased reporting of depressive symptoms compared to both non-pregnant women and exposure to other anti-emetics during pregnancy. This may be explained by a combination of pregnancy-related factors and the pharmacological mechanism of metoclopramide. Given the frequent co-occurrence of suicidal tendency, awareness of this possible ADR is crucial for early recognition and prompt intervention to prevent symptom progression and improve maternal safety.

PMID:41802703 | DOI:10.1016/j.jaclp.2026.03.001