Neonatal withdrawal syndrome following in utero exposure to antidepressants: a disproportionality analysis of VigiBase, the WHO spontaneous reporting database

Psychol Med. 2023 Sep;53(12):5645-5653. doi: 10.1017/S0033291722002859. Epub 2022 Sep 21.


Background: Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs).

Methods: In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared.

Results: A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45-7.01, IC: 2.07, 95% CI 1.92-2.21). Signals were found for TCAs (10.55, 95% CI 8.02-13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74-7.36) and SSRIs (ROR: 4.68, 95% CI 4.04-5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40).

Conclusions: Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.

Keywords: Abstinence syndrome; antidepressants; neonates; poor neonatal adaptation syndrome; pregnancy; withdrawal syndrome.

MeSH terms

  • Antidepressive Agents / adverse effects
  • Bayes Theorem
  • Female
  • Humans
  • Infant, Newborn
  • Methadone
  • Neonatal Abstinence Syndrome* / drug therapy
  • Neonatal Abstinence Syndrome* / epidemiology
  • Neonatal Abstinence Syndrome* / etiology
  • Pregnancy
  • Selective Serotonin Reuptake Inhibitors* / adverse effects
  • World Health Organization


  • Selective Serotonin Reuptake Inhibitors
  • Antidepressive Agents
  • Methadone