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Drug Reference

sertraline

Selective serotonin reuptake inhibitor (SSRI)· Brands: Lustral, ZoloftPO

Mechanism of action
Sertraline is a selective serotonin reuptake inhibitor (SSRI). It inhibits the presynaptic reuptake of serotonin (5-hydroxytryptamine), thereby increasing the concentration of serotonin in the synaptic cleft and enhancing serotonergic neurotransmission. Sertraline has minimal effects on noradrenaline (norepinephrine) or dopamine reuptake, and it has low affinity for other receptors such as adrenergic, histaminergic, and muscarinic receptors. This selectivity contributes to its clinical efficacy in treating major depressive disorder, anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder.
Pharmacokinetics
Sertraline is well absorbed after oral administration, with peak plasma concentrations occurring approximately 4.5 to 8.4 hours after dosing. It has a mean elimination half-life of about 26 hours, allowing once-daily dosing. Sertraline is extensively bound to plasma proteins (approximately 98%). It is metabolized primarily in the liver via cytochrome P450 enzymes, including CYP2B6, CYP2C9, CYP2C19, and CYP3A4, to form N-desmethylsertraline, which is considerably less active than the parent compound. Both sertraline and its metabolite are excreted in urine and faeces as conjugates. The pharmacokinetics are not significantly affected by food, and absorption may be enhanced when taken with food.
Indications & dosing

Major depressive disorder

Start at 50 mg once daily; increase as tolerated. Usual therapeutic range 50-200 mg/day.

  • adult · PO: 50–200 mg once daily · Start at 50 mg once daily; increase as tolerated. Usual therapeutic range 50-200 mg/day.

Obsessive-compulsive disorder (OCD)

Start at 50 mg once daily; may increase to 200 mg/day. For pediatric OCD, see separate indication.

  • adult · PO: 50–200 mg once daily · Start at 50 mg once daily; may increase to 200 mg/day. For pediatric OCD, see separate indication.

Obsessive-compulsive disorder (OCD) in children (6-17 years)

Start at 25 mg once daily (50 mg for ages 13-17); titrate as needed. Usual range 25-200 mg/day.

  • pediatric · PO: 25–200 mg once daily · Start at 25 mg once daily (50 mg for ages 13-17); titrate as needed. Usual range 25-200 mg/day.

Panic disorder

Start at 25 mg once daily for one week, then increase to 50 mg. Usual maintenance 50-200 mg/day.

  • adult · PO: 25–200 mg once daily · Start at 25 mg once daily for one week, then increase to 50 mg. Usual maintenance 50-200 mg/day.

Post-traumatic stress disorder (PTSD)

Start at 50 mg once daily; usual range 50-200 mg/day.

  • adult · PO: 50–200 mg once daily · Start at 50 mg once daily; usual range 50-200 mg/day.

Premenstrual dysphoric disorder (PMDD)

Can be taken daily throughout the cycle or only during the luteal phase, starting at 50 mg/day.

  • adult · PO: 50–150 mg once daily · Can be taken daily throughout the cycle or only during the luteal phase, starting at 50 mg/day.

Social anxiety disorder

Start at 50 mg once daily; usual range 50-200 mg/day.

  • adult · PO: 50–200 mg once daily · Start at 50 mg once daily; usual range 50-200 mg/day.
Contraindications & precautions
  • Hypersensitivity to sertraline or any of its excipients · Avoid in patients with a known allergy to sertraline.
  • Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping an MAOI · Risk of serotonin syndrome. Allow 14 days between stopping an MAOI and starting sertraline, and vice versa.
  • Concomitant use with pimozide · Risk of QT interval prolongation.
  • Uncontrolled epilepsy · May lower the seizure threshold.
  • History of mania or hypomania · May trigger a manic episode.
  • Significant hepatic impairment · Reduce dose or avoid if severe; monitor liver function.
  • Pregnancy, especially third trimester · Use only if benefit outweighs risk; consider neonatal withdrawal syndrome.
  • Breastfeeding · Sertraline is excreted in breast milk; assess risk versus benefit.
  • Monitor for signs of serotonin syndrome (agitation, confusion, tremor, hyperthermia), especially when initiating therapy or increasing the dose; advise caution with other serotonergic drugs.
  • Monitor for new or worsening depression, suicidality, or behavioural changes, particularly in young adults and during the first few weeks of treatment.
  • Use with caution in patients with epilepsy, as sertraline may lower the seizure threshold.
  • Use with caution in patients taking anticoagulants, NSAIDs, or antiplatelets due to increased bleeding risk; consider gastroprotective co-prescription.
  • Caution in hepatic impairment; consider dose reduction and monitor liver function.
  • Advise patients not to stop treatment abruptly, as withdrawal symptoms may occur; taper the dose.
Adverse effects
  • Nausea
  • Diarrhoea
  • Insomnia
  • Headache
  • Tremor
  • Sexual dysfunction (e.g., delayed ejaculation, anorgasmia)
  • Serotonin syndromeserious
  • Hyponatraemiaserious
  • Suicidal ideation or behaviourserious
  • Abnormal bleeding (e.g., ecchymosis, gastrointestinal bleeding)serious
Interactions
  • ibuprofenmajorAvoid concomitant use unless clearly necessary. If the combination is required, consider adding a proton pump inhibitor for gastroprotection, use the lowest effective dose of ibuprofen for the shortest duration, and monitor patients for signs of gastrointestinal bleeding, such as melaena or haemorrhage. Advise patients to report any black stools or unexplained abdominal pain.
  • tramadolmajorAvoid combination where possible. If necessary, use the lowest effective doses, prescribe with extreme caution, and monitor the patient closely for signs of serotonin syndrome (e.g., mental status changes, fever, sweating, tremor, hyperreflexia, clonus). Consider a non-serotonergic analgesic such as an NSAID or a pure opioid (e.g., morphine) as an alternative. Advise the patient to seek urgent medical attention if symptoms occur.
  • sumatriptanmajorIf co-prescription is necessary, monitor patients closely for signs and symptoms of serotonin syndrome. Counsel the patient to seek immediate medical attention if they experience agitation, hallucinations, rapid heart rate, fever, muscle twitching, or diarrhea. Consider alternative migraine therapy with a drug lacking serotonergic activity, such as a nonsteroidal anti-inflammatory agent or an antiemetic. If serotonin syndrome is suspected, stop both drugs and initiate supportive care. Ensure the patient's history is reviewed for other serotonergic medications.
  • aspirinmajorUse with caution. Monitor patients for signs of bleeding, such as anaemia, black stools, or epistaxis. Consider gastroprotective therapy, such as a proton pump inhibitor, especially in patients with risk factors. Weigh the benefits of antiplatelet therapy against the risk of bleeding. If excessive bleeding occurs, review the need for sertraline and consider alternatives.
  • linezolidcontraindicatedDo not co-prescribe linezolid and sertraline. If linezolid is essential, withhold sertraline for at least 5 half-lives before starting linezolid, and resume at least 24 hours after the last dose of linezolid (or longer for long-acting formulations). If urgent concomitant use is unavoidable, closely monitor for signs of serotonin syndrome and consider alternative antibiotics when clinically feasible.
Renal & hepatic adjustment
  • Hepatic impairment (mild): Use with caution, reduce dose if necessary.
  • Hepatic impairment (moderate): Use with caution, consider lower dose or extended dosing interval.
  • Hepatic impairment (severe): Avoid if possible; if treatment is necessary, use with extreme caution and reduce dose. (avoid)
Monitoring, pregnancy & toxicity
  • Mood and suicidal ideation · At initiation and after dose changes, and regularly during treatment.
  • Signs of serotonin syndrome · At each review.
  • Serum sodium · In elderly or at-risk patients, especially during the first month.
  • Signs of abnormal bleeding · If concurrent anticoagulants or NSAIDs.
  • Behavioural changes and suicidality in children and adolescents · Regularly.
  • Pregnancy: Sertraline is considered a preferred SSRI in pregnancy due to its relative safety. Use only if the potential benefit outweighs the risk. Use the lowest effective dose and avoid abrupt discontinuation. Discuss the risks of untreated depression versus fetal exposure with the patient.
  • Toxicity: Serotonin syndrome (agitation, confusion, hyperreflexia, myoclonus, tachycardia, fever) · Stop drug, supportive care, cyproheptadine for severe cases, monitor for autonomic instability.
  • Toxicity: CNS depression (drowsiness, coma) · Airway and ventilatory support, gastric decontamination if recent ingestion, monitor for seizures.
  • Toxicity: Cardiovascular effects (tachycardia, QT prolongation, hypotension) · Continuous ECG monitoring, correct electrolyte abnormalities, consider cardiac consultation.
  • Toxicity: Nausea, vomiting, and diarrhoea · Supportive care, hydration, antiemetics if required.
Clinical notes
Sertraline is commonly used as a first-line treatment for depression and anxiety disorders, including panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder. It is also used for post-traumatic stress disorder. The usual starting dose is 50 mg once daily, with doses titrated up according to response. It has a relatively favorable side-effect profile compared to other SSRIs, with less sedation and weight gain, but it may cause gastrointestinal upset, insomnia, and sexual dysfunction. Sertraline should be used with caution in patients with epilepsy, bipolar disorder, or hyponatraemia, and it is contraindicated with monoamine oxidase inhibitors due to the risk of serotonin syndrome. Abrupt discontinuation should be avoided; the dose should be tapered gradually. Cautions are needed with concurrent use of other serotonergic drugs, anticoagulants, and NSAIDs due to increased bleeding risk. In pregnancy, the benefits and risks should be considered; sertraline is sometimes used during pregnancy but specialist advice is recommended.

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BNF; local formulary