What it is
Sertraline is a selective serotonin reuptake inhibitor (SSRI), first line in depression, generalised anxiety disorder, panic, obsessive-compulsive disorder and post-traumatic stress. It increases the serotonin available in the synapse by blocking its transporter (SERT). It takes 2–4 weeks to work, but it does not cause dependence or tolerance like benzodiazepines.
It is well tolerated long term and has fewer interactions than other SSRIs such as fluoxetine or paroxetine. Stopping it suddenly can cause a discontinuation syndrome, so it is tapered gradually.
Mechanism of action
It blocks:
- The SERT serotonin reuptake transporter
- It increases the serotonin available in the synapse
- A normalising effect on emotional circuits
At the counter
When to recommend it
- Major depression
- Generalised anxiety disorder
- Panic disorder
- PTSD and social phobia
When not to
- Allergy to sertraline
- An MAOI in the last two weeks, or pimozide (contraindicated)
- Angle-closure glaucoma (caution)
- Risk of hyponatraemia —older people, diuretics— (caution)
Warnings
- Important Serotonin syndrome: rare but serious with MAOIs, tramadol, triptans, other antidepressants, St John's wort or MDMA. Agitation, fever, tremor, rigidity.
- Important Suicidal thoughts: especially in young people during the first weeks. Monitor.
- Caution Bleeding: with NSAIDs, aspirin or anticoagulants it increases the risk of haemorrhage, especially gastrointestinal.
- Caution Discontinuation syndrome: headache and dizziness if stopped suddenly. Taper gradually.
Pharmacokinetics
- Absorption
- Slow oral absorption. Food increases it slightly. Peak at 4–8 hours.
- Distribution
- Wide distribution. Protein binding of 98%. It crosses the blood–brain barrier adequately.
- Metabolism
- Extensive hepatic metabolism via CYP2D6 and CYP3A4. It produces metabolites with minimal activity.
- Elimination
- Renal elimination of metabolites. Half-life of 24–26 hours, allowing a single daily dose.
Sertraline vs alprazolam
| Aspect | Sertraline | Alprazolam |
|---|---|---|
| Onset of effect | Slow (2–4 weeks) | Fast (15–30 min) |
| Dependence | No | Yes |
| Long-term use | Recommended | NOT recommended |
| Acute anxiety | Not effective at first | Excellent |
| Best combination | Core (maintenance) | Temporary bridge (a few weeks) |
Sertraline is the long-term core treatment. Alprazolam is a temporary bridge for the initial acute symptoms.
Self-assessment
Three questions. When you check your answers you will see the explanation for each one.
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Sertraline needs 2–4 weeks for its full effect (synaptic changes). That is why it is sometimes combined with a benzodiazepine at the start.
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SSRIs need 2–4 weeks to start being noticeable. Stopping in the first week is the most frequent cause of 'it didn't work for me'. Adjusting the dose or switching is the doctor's decision.
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Sexual dysfunction is common with SSRIs and under-reported. It is reversible and can be managed: the patient should talk to their doctor about it rather than abandon treatment.
Training content. It does not replace the summary of product characteristics or clinical judgement.