Pharmacology · Class

Selective serotonin reuptake inhibitors (SSRIs) !

First-line antidepressants that block the serotonin transporter, so more serotonin stays in the synapse. Safer in overdose than older antidepressants.

Updated 2026-11-01

What they are

The most prescribed antidepressants, used for depression and for anxiety disorders, obsessive-compulsive disorder, panic disorder and bulimia. They take weeks to work fully, and they are much safer in overdose than tricyclics or MAO inhibitors.

Mechanism of action

SSRIs bind the central site of the serotonin transporter (SERT, gene SLC6A4) on the presynaptic neuron and block reuptake of serotonin from the synapse. Serotonin signalling rises within hours, but the mood effect takes weeks, which is thought to reflect slower adaptive changes such as desensitisation of inhibitory 5-HT1A autoreceptors.

Target: Serotonin transporter (SERT, SLC6A4)

Key points

Boxed warning: more suicidal thoughts and behaviour in children, adolescents and young adults early in treatment and after dose changes; watch closely in every age group.
Serotonin syndrome: risk rises with other serotonergic drugs (MAO inhibitors, linezolid, triptans, tramadol, fentanyl, lithium, St John's wort). MAO inhibitors are contraindicated with them, with a washout set by each label.
Discontinuation syndrome after abrupt stopping: dizziness, electric-shock sensations, irritability, nausea, insomnia. Tapering lowers the risk; fluoxetine's long half-life makes it least likely.
Class effects: sexual dysfunction, hyponatraemia (SIADH, especially in older adults), higher bleeding risk with NSAIDs, aspirin or warfarin, and switch to mania in undiagnosed bipolar disorder.
Late-pregnancy exposure is linked to persistent pulmonary hypertension and poor adaptation in the newborn.

Drugs in this class

Others in the class

Fluvoxamine

Test yourself

Think of the answer, then tap the question to see it.

Why does an SSRI take weeks to improve mood when it blocks serotonin reuptake within hours?

The clinical effect is thought to depend on slower adaptive changes, such as desensitisation of inhibitory 5-HT1A autoreceptors and downstream changes in signalling, not on the immediate rise in synaptic serotonin.

Which group of patients carries the boxed warning on SSRIs, and what does it say?

Children, adolescents and young adults: in short-term trials antidepressants increased suicidal thoughts and behaviour. All patients are watched closely when treatment starts and when the dose changes.

A patient on an SSRI starts tramadol and develops agitation, sweating, tremor, clonus and fever. What is the diagnosis?

Serotonin syndrome: excess serotonergic activity with mental status change, autonomic instability and neuromuscular signs (clonus, hyperreflexia). Both drugs are stopped and care is supportive.

Which electrolyte problem do SSRIs cause, and who is most at risk?

Hyponatraemia, usually from SIADH. Older adults, people on diuretics and volume-depleted patients are most at risk.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - SERTRALINE HYDROCHLORIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - FLUOXETINE capsule (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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