The effect of SSRIs on fear learning: A systematic review and meta-analysis

Elise J. Heesbeen, Elisabeth Y. Bijlsma, P. Monika Verdouw, Caspar van Lissa, Carlijn Hooijmans, Lucianne Groenink

Research output: Contribution to journalReview articlepeer-review

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Abstract

RationaleSelective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known.ObjectiveWe aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear.MethodsWe searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments.ResultsMeta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes.ConclusionsThis review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs.
Original languageEnglish
Pages (from-to)2335-2359
JournalPsychopharmacology
Volume240
Issue number11
DOIs
Publication statusPublished - 2023

Keywords

  • 5-HT re-uptake inhibitor
  • Acquisition
  • Anxiety
  • Contextual anxiety
  • Extinction
  • Fear conditioning
  • Fear learning
  • Meta-analysis
  • SSRIs
  • Systematic review

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