Selective serotonin reuptake inhibitors (SSRI) 💊
💊 SSRIs (Selective Serotonin Reuptake Inhibitors) are usually the first-choice antidepressant class for depression in adults due to their safety profile, particularly in overdose.
⏳ Full response may take ≥6 weeks, and treatment should continue for at least 6 months after recovery to reduce relapse risk.
📖 About
- Less cardiotoxic and with fewer muscarinic side effects than TCAs.
- Some newer agents (SNRIs) also block noradrenaline reuptake, offering broader efficacy.
- Check BNF here for prescribing details.
⚙️ Mechanism of Action
- SSRIs: Inhibit serotonin reuptake → ↑ serotonin in synaptic cleft.
- SNRIs: Block serotonin and noradrenaline reuptake (e.g., venlafaxine, duloxetine).
- Improves mood, anxiety, and related symptoms over time.
🎯 Indications
- Depression in adults - the usual first-choice antidepressant class when medication is chosen (NICE NG222).
- Anxiety disorders (GAD, panic disorder, social anxiety, OCD, PTSD).
- Bulimia nervosa (fluoxetine licensed).
- Premenstrual dysphoric disorder.
💊 Common SSRIs (typical adult doses)
- Fluoxetine: start 20 mg OD → max 60 mg.
- Citalopram: start 20 mg OD → up to 40 mg (max 20 mg if over 65 or hepatic impairment; QT caution).
- Sertraline: start 50 mg OD → up to 200 mg.
- Paroxetine: start 20 mg OD → up to 50 mg.
⚠️ Side Effects (serotonin-related)
- Nausea, diarrhoea, dyspepsia.
- Insomnia or excessive somnolence.
- Sexual dysfunction (reduced libido, delayed orgasm, erectile dysfunction) - common and under-reported.
- Headache, dizziness, sweating, tremor, dry mouth.
- Early agitation and anxiety; rarely akathisia.
- Hyponatraemia (SIADH) - especially older people and those on diuretics; check sodium if drowsy, confused or seizing.
- Bleeding (↓ platelet serotonin) - particularly upper GI bleeding with NSAIDs, aspirin or anticoagulants; consider a PPI.
- QT prolongation - citalopram and escitalopram (dose limits; avoid with other QT-prolonging drugs).
- Suicidal thoughts - increased risk early in treatment in people under 25; review within 1 week of starting in this group.
- Weight change; rarely mania/hypomania, seizures, bruxism.
🔄 Interactions
- Serotonin syndrome risk with MAOIs (contraindicated), linezolid, tramadol, triptans, St John's wort, lithium, other antidepressants, fentanyl, methylene blue.
- Bleeding risk with NSAIDs, aspirin, warfarin and DOACs.
- CYP2D6 inhibition by fluoxetine and paroxetine → ↑ levels of TCAs, some antipsychotics and beta-blockers; ↓ activation of tamoxifen and codeine.
- Citalopram/escitalopram + other QT-prolonging drugs: avoid.
⚠️ Cautions
- Epilepsy (lowers seizure threshold), bipolar disorder (risk of switching to mania), bleeding disorders.
- Older people (hyponatraemia, falls), diabetes, cardiac disease (citalopram).
- Pregnancy: small risks (e.g. persistent pulmonary hypertension of the newborn, neonatal adaptation syndrome) - balance against the risk of untreated depression; sertraline is commonly used.
- Citalopram: max 20 mg daily if aged over 65 or with hepatic impairment.
🚫 Contraindications
- Mania (active manic phase).
- MAOI use within the previous 14 days (and wait at least 5 weeks after stopping fluoxetine before starting an MAOI).
- Citalopram/escitalopram: known QT prolongation or congenital long-QT syndrome.
🛑 Stopping (Discontinuation)
- Taper gradually over weeks, or longer after long-term use (NICE NG222); paroxetine has the worst discontinuation symptoms, fluoxetine the least (long half-life).
- Symptoms: dizziness, "electric shock" sensations, anxiety, irritability, insomnia, flu-like symptoms, GI upset.
👶 Children and Young People
- Antidepressants are not first line in under-18s. Fluoxetine is the only SSRI recommended (licensed from age 8), with psychological therapy and specialist (CAMHS) supervision.
📚 References
