Selective serotonin reuptake inhibitors (SSRIs)
ATC code: N06AB06 (Sertraline)
Brand names
Zoloft
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.
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.
First line
Sertraline is a first-line agent for major depression in adults per 2023 and 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.
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.
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.
First line
Sertraline is one of two -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.
11 pairs found. Sorted from critical to minor.
Mechanism
Линезолид – обратимый ингибитор МАО, в сочетании с вызывает тяжелый серотониновый синдром.
Management
Сочетание противопоказано. отменить за 2 недели до старта линезолида (для флуоксетина – за 5 недель).
Mechanism
Both drugs prolong the QT interval (amiodarone strongly via IKr potassium channel blockade; sertraline modestly). Additive QT prolongation increases the risk of torsades de pointes, especially with hypokalemia and hypomagnesemia.
Management
Obtain a baseline ECG (QTc) and repeat 1–2 weeks after starting or increasing sertraline. QTc > 500 ms or an increase > 60 ms warrants reassessment. Keep potassium ≥ 4.0 mmol/L and magnesium ≥ 1.0 mmol/L. Antidepressant alternatives with minimal QT effect include mirtazapine and bupropion.
Sources
Mechanism
SSRIs deplete platelet serotonin and impair primary hemostasis. Combined with apixaban, the risk of major GI bleeding rises roughly 1.5-fold.
Management
If depression requires treatment, prescribe the SSRI and add a PPI (pantoprazole) if GI bleeding risk factors are present. Alternatives include mirtazapine and agomelatine (minimal serotonergic activity).
Sources
Mechanism
Additive QT prolongation: sertraline modestly and ciprofloxacin modestly. In older patients with additional factors (hypokalemia, bradycardia, female sex), torsades de pointes risk increases. Ciprofloxacin also weakly inhibits CYP enzymes, potentially raising sertraline concentration slightly.
Management
Obtain a baseline ECG when prescribing ciprofloxacin to a patient on sertraline. Keep potassium above 4.0 mmol/L. If QTc exceeds 500 ms, switch to a non-fluoroquinolone antibiotic.
Sources
Mechanism
Аддитивное серотонинергическое действие + индукция CYP3A4 зверобоем, снижающая концентрации множества препаратов.
Management
Избегать сочетания. Если пациент уже принимает зверобой – отменить за 2 недели до начала .
Mechanism
Аддитивное серотонинергическое действие. Риск серотонинового синдрома.
Management
Избегать. Если применять – минимальные дозы, мониторинг неврологического статуса.
Mechanism
Dual mechanism: 1) sertraline inhibits serotonin reuptake in platelets, depleting platelet serotonin and reducing aggregation; 2) moderate CYP2C9 inhibition raises warfarin concentration and INR. GI bleeding risk roughly doubles.
Management
When starting sertraline in a warfarin-treated patient, check INR at 1, 2, and 4 weeks. Add a PPI (pantoprazole) if GI bleeding risk factors are present. Alternatives include mirtazapine (less serotonergic activity) or agomelatine.
Sources
Mechanism
Two effects: 1) clopidogrel blocks aggregation at the P2Y12 receptor while sertraline impairs primary hemostasis by inhibiting platelet serotonin reuptake; 2) sertraline weakly inhibits CYP2C19 – clopidogrel activation is slightly reduced.
Management
Watch for bleeding signs. With elevated GI risk, add a PPI (pantoprazole, not omeprazole). Antidepressant alternatives with minimal platelet effects include mirtazapine and bupropion.
Sources
Mechanism
Both drugs can cause hyponatremia (furosemide via natriuresis, sertraline via an SIADH-like mechanism). In patients over 75, the rate of clinically significant hyponatremia (Na+ < 130 mmol/L) rises with the combination.
Management
Check sodium at baseline, at 2 and 4 weeks after sertraline initiation, then every 3–6 months. For Na+ < 130 mmol/L, reassess therapy.
Sources
Mechanism
Thiazides are one of the commonest drug causes of hyponatremia in older adults (via an SIADH-like mechanism plus natriuresis). SSRIs add their own SIADH effect. Additive risk of severe hyponatremia (Na+ < 125 mmol/L) with confusion, seizures, and falls.
Management
Check sodium at baseline, at 1, 2, and 4 weeks after sertraline initiation, then every 3 months. In patients over 75 with sodium < 135 mmol/L, optimize the thiazide or switch the antidepressant.
Sources
Mechanism
Omeprazole inhibits CYP2C19 – sertraline concentration rises by roughly 40 %. Clinically, side effects may intensify: nausea, diarrhea, insomnia, agitation, QT prolongation.
Management
With concurrent use in CYP2C19 poor metabolizers, start sertraline at the lowest dose (25 mg) and titrate more slowly. Obtain an ECG when QT-prolongation risk factors are present.
Sources
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.
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.
Compatible with breastfeeding: sertraline and its metabolite pass into milk in very low concentrations; one of the preferred SSRIs during lactation.
sertraline is evaluated for the following indications with varying evidence strength: Major depressive disorder (evidence tier A), Generalized anxiety disorder (evidence tier A), Post-traumatic stress disorder (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of sertraline (≥ 1 in 100): Nausea, especially in the first 1–2 weeks, Diarrhea, Sleep disturbance (insomnia or somnolence), Sexual dysfunction (reduced libido, delayed ejaculation, anorgasmia), Sweating, Tremor. See the Safety section for uncommon and serious reactions.
FDA category 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.
Compatible with breastfeeding: sertraline and its metabolite pass into milk in very low concentrations; one of the preferred SSRIs during lactation.
sertraline is contraindicated in: Concurrent use with MAO inhibitors (within 14 days before or after); Concurrent use with pimozide; Hypersensitivity to any component. Full list in the Safety section.
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.
SSRIs do not cause chemical dependence or craving, but can cause a discontinuation syndrome on abrupt cessation — gradual tapering is required.
therapy restores normal emotional function in patients with depression, anxiety, or OCD. Feeling 'like a different person' typically resolves once the dose stabilizes.
after a first depressive episode, therapy is usually continued 6–12 months after remission, then tapered. Recurrent disease requires individualized duration.