ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2024
Rebound activation of 5-HT neurons following SSRI discontinuation.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2024. 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.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Deprescribing Antidepressants in Children and Adolescents: A Systematic Review of Discontinuation Approaches, Cross-Titration, and Withdrawal Symptoms.Journal of child and adolescent psychopharmacology · 2025Pooled it
- The neuropsychopharmacology of treatment discontinuation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Psychopharmacological Mechanisms of Antidepressant Withdrawal: Insights From Venlafaxine.Human psychopharmacology · 2026Review
- Curculigoside Alleviates CSDS-induced Depressive-like Behavior by Modulating Pyramidal Neuron Excitability and Synaptic Transmission.Neuromolecular medicine · 2026Article
- Synchronous activation of striatal cholinergic interneurons induces local serotonin release.Nature communications · 2026Article
- Beyond Organ Boundaries: Molecular Mechanisms of Hepatic Encephalopathy and Parkinson's Disease from the Perspective of the Gut-Liver-Brain Axis.Research (Washington, D.C.) · 2026Review
- Association between the combination of GABAergic agents and SSRIs at the first clinical visit and depressive symptom trajectories: A study using group-based trajectory modeling and Apriori algorithm.PLOS mental health · 2026Article
- [Electroacupuncture improves post-traumatic stress disorder in rats by alleviating hippocampal mitochondrial injuryNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Increased c-Fos immunoreactivity in anxiety-related brain regions following paroxetine discontinuation.Neuropharmacology · 2025Article
- Selective serotonin reuptake inhibitors induce cardiac toxicity through dysfunction of mitochondria and sarcomeres.Communications biology · 2025Article
- Reduction of Prostate Cancer Risk: Role of Frequent Ejaculation-Associated Mechanisms.Cancers · 2025Review
- Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors.Biomedicines · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Cessation of therapy with a selective serotonin (5-HT) reuptake inhibitor (SSRI) is often associated with an early onset and disabling discontinuation syndrome, the mechanism of which is surprisingly little investigated. Here we determined the effect on 5-HT neurochemistry of discontinuation from the SSRI paroxetine. Paroxetine was administered repeatedly to mice (once daily, 12 days versus saline controls) and then either continued or discontinued for up to 5 days. Whereas brain tissue levels of 5-HT and/or its metabolite 5-HIAA tended to decrease during continuous paroxetine, levels increased above controls after discontinuation, notably in hippocampus. In microdialysis experiments continuous paroxetine elevated hippocampal extracellular 5-HT and this effect fell to saline control levels on discontinuation. However, depolarisation (high potassium)-evoked 5-HT release was reduced by continuous paroxetine but increased above controls post-discontinuation. Extracellular hippocampal 5-HIAA also decreased during continuous paroxetine and increased above controls post-discontinuation. Next, immunohistochemistry experiments found that paroxetine discontinuation increased c-Fos expression in midbrain 5-HT (TPH2 positive) neurons, adding further evidence for a hyperexcitable 5-HT system. The latter effect was recapitulated by 5-HT
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Registered trials
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.