Skip to content

Mechanisms of SSRI Therapy and Discontinuation.

Trevor Sharp, Helen M Collins

Current Topics in Behavioral Neurosciences 2024 DOI: 10.1007/7854_2023_452 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Anxiety Depression Ketamine Neuroplasticity Serotonin
Keywords Antidepressants Citalopram Discontinuation Fluoxetine Paroxetine Psychedelics Ssris Serotonin 5-HT Receptors Withdrawal
Citations 40
Key findings SSRIs' therapeutic effects are now thought to involve complex downstream signaling that triggers neural plasticity, but evidence causally linking plasticity to behavioral effects is missing, and the mechanisms of SSRI discontinuation syndrome remain poorly understood.

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.

Comparable studies

Other narrative reviews on ketamine for anxiety, most cited first.

Study Year Design Participants
A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders 2017 Review and consensus statement
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS 2016 Review
Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors 2018 Review
Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... 2018 Narrative review
Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions 2013 Review

Citations in the library

Cited by 7

and 2 more in the library

Cites 19

and 14 more in the library

Related reading

Explore topics

Anxiety Depression Ketamine Neuroplasticity Serotonin Psychedelic-assisted therapy

By condition and practice

Ketamine for anxiety Ketamine for depression