Evidence map›Paper›PMID 37955823›Full record

ReviewCurrent topics in behavioral neurosciences2024

Mechanisms of SSRI Therapy and Discontinuation.

Trevor Sharp, Helen Collins

Abstract readReview
PubMed Publisher
In one paragraph

Review in Current topics in behavioral neurosciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 2 pooled it
49.6field-weighted citation impact, top 1% 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

28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Early effects of a novel 5-HTThe British journal of psychiatry : the journal of mental science · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Involvement of Serotonergic and Dopaminergic Systems inPharmaceuticals (Basel, Switzerland) · 2026
    Article
  10. Review
  11. Review
  12. Understanding the emergence of suicidal thoughts and behaviors in adolescence from a brain and behavioral developmental perspective.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  13. Review
  14. Transforming Amino Acids into Serotonin 5-HTJournal of the American Chemical Society · 2025
    Article
  15. Review
  16. Article
  17. Review
  18. The psychedelic-peptide paradox: a hormetic hypothesis.Comprehensive psychoneuroendocrinology · 2025
    Review
  19. Article
  20. 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

2 authors at 1 institution in 1 country.

Trevor SharpDepartment of Pharmacology, University of Oxford, Oxford, UK. trevor.sharp@pharm.ox.ac.uk.
Helen CollinsDepartment of Pharmacology, University of Oxford, Oxford, UK.
University of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SSRIs are one of the most widely used drug therapies in primary care and psychiatry, and central to the management of the most common mental health problems in today's society. Despite this, SSRIs suffer from a slow onset of therapeutic effect and relatively poor efficacy as well as adverse effects, with recent concerns being focused on a disabling SSRI discontinuation syndrome. The mechanism underpinning their therapeutic effect has long shifted away from thinking that SSRIs act simply by increasing 5-HT in the synapse. Rather, a current popular view is that increased 5-HT is just the beginning of a series of complex downstream signalling events, which trigger changes in neural plasticity at the functional and structural level. These changes in plasticity are then thought to interact with neuropsychological processes to enhance re-learning of emotional experiences that ultimately brings about changes in mood. This compelling view of SSRI action is underpinning attempts to understand fast-acting antidepressants, such as ketamine and psychedelic drugs, and aid the development of future therapies. An important gap in the theory is evidence that changes in plasticity are causally linked to relevant behavioural effects. Also, predictions that the SSRI-induced neural plasticity might have applicability in other areas of medicine have not yet been borne out. In contrast to the sophisticated view of the antidepressant action of SSRIs, the mechanism underpinning SSRI discontinuation is little explored. Nevertheless, evidence of rebound increases in 5-HT neuron excitability immediately on cessation of SSRI treatment provide a starting point for future investigation. Indeed, this evidence allows formulation of a mechanistic explanation of SSRI discontinuation which draws on parallels with the withdrawal states of other psychotropic drugs.

Indexed as

Neuronal PlasticitySelective Serotonin Reuptake InhibitorsAnimalsAntidepressive AgentsHumansSerotoninSubstance Withdrawal SyndromeAntidepressive AgentsSelective Serotonin Reuptake InhibitorsSerotoninAntidepressantsAnxietyCitalopramDepressionDiscontinuationFluoxetineKetamineNeural plasticityParoxetinePsychedelicsSerotoninSerotonin (5-HT) receptorsSSRIsWithdrawal

Identifiers

PMID37955823
OpenAlexW4388641323

What Socratic holds

Textmetadata
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 Socratic graph.