Sertraline

Sertraline is an SSRI used for depression, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder and social anxiety disorder. It has the most evidence for cardiac safety after acute coronary syndrome, low infant exposure in breastfeeding, and little sedation, with diarrhoea as a leading adverse effect.

Classification. SSRI, naphthylamine structure.

Mechanism. Potent inhibition of the serotonin transporter with weak effects on dopamine reuptake and sigma-1 receptors. Response builds over 2 to 4 weeks.

Pharmacokinetics. Absorption is improved slightly by food. Extensive hepatic metabolism by several CYP enzymes to desmethylsertraline, which is weakly active. Half-life about 26 hours (desmethylsertraline 62 to 104 hours). Weak to moderate CYP2D6 inhibition at 150 mg and over.

All regimens are oral with no loading dose.

Major depression, adults (first-line).

• Start 50 mg once daily.
• Titration: increase in steps of 25 to 50 mg at intervals of at least 1 week.
• Maintenance 50 to 200 mg daily. Maximum 200 mg daily.
• Duration: at least 6 months after remission; 2 years or more for recurrent illness.

Obsessive-compulsive disorder. Start 50 mg daily, increase in steps of 25 to 50 mg at intervals of at least 1 week to a usual 100 to 200 mg daily. Maximum 200 mg. Judge response after 8 to 12 weeks.

Panic disorder, post-traumatic stress disorder, social anxiety disorder. Start 25 mg daily for 1 week to limit early anxiety, then 50 mg daily; titrate by 25 to 50 mg at weekly intervals. Maximum 200 mg daily.

Children aged 6 to 17 years with obsessive-compulsive disorder. Aged 6 to 12 years start 25 mg daily; aged 13 to 17 years start 50 mg daily. Titrate at weekly intervals. Maximum 200 mg daily.

Premenstrual dysphoric disorder (licensed in some regions). 50 mg daily continuously or in the luteal phase only, increased to a maximum of 150 mg (continuous) or 100 mg (luteal).

Contraindications. MAOI use now or within 14 days of stopping it, pimozide, linezolid, intravenous methylene blue, hypersensitivity.

Serious adverse effects. Boxed-warning-level risk of suicidal thinking and behaviour in under 25 years. Serotonin syndrome, hyponatraemia, bleeding, mania, seizures, QT prolongation (uncommon), angle-closure glaucoma, abnormal liver tests.

Common adverse effects. Diarrhoea, nausea, insomnia or somnolence, headache, tremor, sexual dysfunction, sweating.

Interactions. Bleeding risk rises with NSAIDs, aspirin and anticoagulants. Serotonin syndrome risk rises with tramadol, triptans, linezolid, lithium and St John’s wort. Levels of tricyclic antidepressants and flecainide may rise at higher sertraline doses. Warfarin effect can change, so check INR after starting or stopping.

Common prescribing errors. Starting at 50 mg in anxiety disorders without a lower first week; escalating faster than weekly; missing hyponatraemia in older adults.

Special groups.

• Pregnancy: among the SSRIs most often chosen when treatment is needed. Small risks of neonatal adaptation symptoms with late exposure and of persistent pulmonary hypertension of the newborn.
• Breastfeeding: low infant levels; a preferred SSRI.
• Children: licensed from 6 years for obsessive-compulsive disorder only.
• Older adults: effective and relatively well tolerated; check sodium and bleeding risk.
• Kidney impairment: no adjustment; not removed by dialysis.
• Liver impairment: mild, use half the usual dose or give less often; moderate to severe, avoid or use only with specialist advice.

Formulations. Tablets 25 mg, 50 mg and 100 mg; oral concentrate 20 mg/mL, which must be diluted in at least 120 mL of water or juice just before use and may contain alcohol. Give once daily, morning or evening, with or without food.

Baseline. Mood history including past mania, suicide risk, sodium in older adults or those on diuretics, bleeding risk, medicines list, pregnancy status.

Monitoring. Review within 1 to 2 weeks of starting and after each dose change for suicidality and activation. Check sodium 2 to 4 weeks after starting in high-risk patients; review the need for the drug if sodium falls under 130 mmol/L and stop it if under 125 mmol/L or if symptomatic. If there is no improvement after 4 to 6 weeks at an adequate dose, increase the dose or switch.

Stopping. Taper over at least 4 weeks, in steps of 25 to 50 mg every 1 to 2 weeks.

Referral and escalation. Refer to psychiatry for suicidal intent, psychosis, mania, or failure of two adequate courses. Suspected serotonin syndrome needs emergency care.