Sertraline

Selective serotonin reuptake inhibitors (SSRIs)

ATC code: N06AB06 (Sertraline)

Brand names

Zoloft

Mechanism of action

Selectively blocks presynaptic serotonin reuptake, increasing serotonin concentration in the synaptic cleft and postsynaptic receptor activation. Minimal effect on norepinephrine and dopamine reuptake. Lacks anticholinergic, antihistamine, and alpha-adrenergic activity, which explains better tolerability compared with tricyclic antidepressants.

Indications

Generalized anxiety disorder

First line

First-line therapy for generalized anxiety disorder in adults alongside escitalopram and venlafaxine. The response is slower than in depression (typically 6–8 weeks). Initial anxiety worsening may occur and should be discussed with the patient. Taper gradually on discontinuation.

Sources

NICE: Generalised anxiety disorder and panic disorder in adults: management (CG113) (2020)

Major depressive disorder

First line

Sertraline is a first-line agent for major depression in adults per APA 2023 and NICE NG222. Starting dose 50 mg once daily in the morning, maximum 200 mg. Response is assessed at 4–6 weeks. If remission is not achieved, options include dose escalation, switching, or combining with psychotherapy. Maintenance after a first episode is at least 6–9 months from the point of remission; recurrent disease requires years of therapy.

Sources

Obsessive-compulsive disorder

First line

OCD requires higher doses than depression (often 150–200 mg daily). The response develops more slowly — assess at 8–12 weeks. Combination with exposure and response prevention (ERP) yields the best outcome.

Sources

NICE: Obsessive-compulsive disorder and body dysmorphic disorder (CG31) (2019)

Panic disorder

First line

First-line therapy for panic disorder with or without agoraphobia. Start at low doses (25 mg daily for the first week) to minimize initial anxiety worsening, then titrate to therapeutic doses. CBT has comparable efficacy and is recommended concurrently or as an alternative.

Sources

NICE: Generalised anxiety disorder and panic disorder in adults: management (CG113) (2020)

Post-traumatic stress disorder

First line

Sertraline is one of two FDA-approved SSRIs for PTSD (the other is paroxetine). A first-line pharmacotherapy alongside psychotherapy (EMDR, trauma-focused CBT). Effect is assessed at 8–12 weeks.

Sources

APA: Practice Guideline for the Treatment of Patients with Major Depressive Disorder (2023)

Practical notes

Timing and administration

Take once daily, usually in the morning. In patients with sleep disturbance, evening dosing is possible, although sertraline may cause activation and worsen sleep in some. Take with food — this reduces GI side effects, especially early in therapy.

Dose titration

Start at 50 mg daily (25 mg in panic disorder or marked anxiety). After 1–2 weeks of good tolerance, increase to 100 mg. Further escalation if response is inadequate, up to a maximum of 200 mg. Tapering on discontinuation should also be gradual: typically 50 mg every 1–2 weeks to prevent discontinuation syndrome.

Monitoring

Clinical monitoring of efficacy and side effects at 2–4 weeks after initiation and any dose change. In patients under 25, pay particular attention to suicidal ideation and behavior during the first weeks. Check serum sodium in older patients, those on diuretics, and those with recent hyponatremia.

Common myths

Myth: 'antidepressants cause dependence'. Fact: SSRIs do not cause chemical dependence or craving, but can cause a discontinuation syndrome on abrupt cessation — gradual tapering is required. Myth: 'antidepressants change personality'. Fact: therapy restores normal emotional function in patients with depression, anxiety, or OCD. Feeling 'like a different person' typically resolves once the dose stabilizes. Myth: 'take them for life'. Fact: after a first depressive episode, therapy is usually continued 6–12 months after remission, then tapered. Recurrent disease requires individualized duration.

Safety

Boxed warning

FDA boxed warning: antidepressants increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults under 25. Special monitoring during the first months of therapy and at dose changes.

Contraindications

Concurrent use with MAO inhibitors (within 14 days before or after)
Concurrent use with pimozide
Hypersensitivity to any component

Serious adverse effects

Serotonin syndrome (when combined with other serotonergic drugs)
Suicidal ideation and behavior in patients under 25
Discontinuation syndrome on abrupt cessation
Hyponatremia (SIADH), especially in the elderly
Increased bleeding risk (with anticoagulants and NSAIDs)
QT prolongation (at high doses, rare)

Common adverse effects

Nausea, especially in the first 1–2 weeks
Diarrhea
Sleep disturbance (insomnia or somnolence)
Sexual dysfunction (reduced libido, delayed ejaculation, anorgasmia)
Sweating
Tremor
Dry mouth

Uncommon adverse effects

Initial anxiety and agitation
Headache
Dizziness
Weight loss or weight gain

PregnancyFDA C

FDA category C. Large cohort studies have not shown significant teratogenic risk. Third-trimester exposure may cause neonatal adaptation syndrome (transient irritability, feeding difficulties) and rarely persistent pulmonary hypertension of the newborn. The decision to continue or discontinue is made with a psychiatrist weighing relapse risk.

Breastfeeding

Compatible with breastfeeding: sertraline and its metabolite pass into milk in very low concentrations; one of the preferred SSRIs during lactation.