Evidence map›Paper›PMID 36847831›Full record

SynthesisPsychopharmacology2023

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

Open access · hybridAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Psychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Methylone promotes neurite outgrowth and has long-lasting effects on fear extinction learning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  7. Article
  8. ACS chemical neuroscience · 2025
    Article
  9. Article
  10. Review
  11. Review
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Elise J HeesbeenDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
Elisabeth Y BijlsmaDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
P Monika VerdouwDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
Caspar van LissaDepartment of Methodology, Tilburg University, Tilburg, Netherlands.
Carlijn HooijmansDepartment of Anaesthesiology, Pain and Palliative Care, Radboud University Medical Center, Nijmegen, Netherlands.
Lucianne GroeninkDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands. l.groenink@uu.nl.ORCID http://orcid.org/0000-0002-4971-7796
Utrecht University · NLRadboud University Nijmegen · NLTilburg University · NL

Funding

ZonMw MKMD 114024147
6 · The paper itself

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.

Indexed as

Selective Serotonin Reuptake InhibitorsStress Disorders, Post-TraumaticAnimalsAnxiety DisordersBayes TheoremFearHumansSelective Serotonin Reuptake Inhibitors5-HT re-uptake inhibitorAcquisitionAnxietyContextual anxietyExtinctionFear conditioningFear learningMeta-analysisSSRIsSystematic review

Identifiers

PMID36847831
PMCPMC10593621
OpenAlexW4322499944

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.