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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Sertraline is an SSRI antidepressant. It is prescribed for depression, generalized anxiety disorder, panic disorder, OCD, PTSD, social anxiety, and PMDD ( 2022, NG222, and WFSBP 2023 guidelines). For burnout or productivity improvement in people without a psychiatric diagnosis, sertraline does not work: no clinical studies of such use exist. Sertraline is one of the most prescribed SSRIs, but this does not mean it is safe for everyone. Risks: sexual dysfunction (often persistent after discontinuation), gastrointestinal upset, hyponatremia, discontinuation syndrome, and increased suicide risk in young adults ( boxed warning). For genuine burnout, other approaches work: workload review, psychotherapy, sleep normalization; for confirmed depression or anxiety, sertraline can help, but that is a diagnosis-based prescription. If sertraline was prescribed for productivity, consider seeking a second opinion.
26 pairs found. Sorted from critical to minor.
Mechanism
Linezolid is an oxazolidinone antibiotic that also reversibly inhibits monoamine oxidase (MAO). Sertraline, a selective serotonin reuptake inhibitor (SSRI), raises synaptic serotonin. Combined action sharply amplifies serotonergic transmission. The carries a boxed warning for this combination.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
The combination is not prescribed. Stop sertraline at least 2 weeks before starting linezolid (washout). If urgent antibiotic therapy is needed, use vancomycin, daptomycin, or ceftaroline based on susceptibility. If serotonin syndrome has already developed, stop both drugs immediately, start cyproheptadine, and admit for intensive supportive care.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
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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.
Sertraline is evaluated for the following indications with varying evidence strength: Post-traumatic stress disorder (evidence tier A), Generalized anxiety disorder (evidence tier A), Major depressive 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.
Mechanism
Methylene blue (methylthioninium chloride) given intravenously is a potent reversible MAO-A inhibitor. Sertraline (SSRI) raises synaptic serotonin. Co-administration sharply amplifies serotonergic transmission.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. IV methylene blue is reserved for emergencies (methaemoglobinaemia, septic shock), and sertraline is stopped at least 5 days before any planned dose. For emergency use on an SSRI, monitor temperature, pulse, and muscle tone in ICU with cyproheptadine available.
Mechanism
Sertraline is an SSRI. Combined with phenelzine causes serotonin syndrome. Nardil Section 4 contraindication. 2-week washout between stopping sertraline and starting phenelzine.
Symptoms
Agitation, tachycardia, hyperthermia, myoclonus within hours of co-administration.
Management
Combination contraindicated. Minimum 2-week washout. After phenelzine withdrawal – 2 weeks before any serotonergic drug.
Mechanism
Sertraline (SSRI) depletes the platelet serotonin pool, weakening platelet aggregation. Aspirin irreversibly blocks platelet cyclooxygenase. Combined, GI bleeding risk roughly doubles.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Severe cases include gastrointestinal or intracranial haemorrhage.
Management
The combination is acceptable at low aspirin doses (75–100 mg as cardioprotection). PPI cover with pantoprazole is mandatory. Alternative antidepressants with minimal platelet effect: mirtazapine or agomelatine.
Sources
Mechanism
Both drugs prolong QT. Amiodarone strongly (via IKr potassium channel block), sertraline dose-dependently and more weakly. Effects add up, especially at high sertraline doses (>100 mg/day) and risk factors: hypokalaemia, female sex, older age.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is acceptable at low sertraline doses (≤100 mg/day) and normal potassium and magnesium. ECG before start and at 2 weeks. Alternative antidepressants with minimal QT effect: mirtazapine or agomelatine.
Sources
Mechanism
Dual risk. Sertraline blocks CYP2D6 – the amitriptyline metabolic route – and amitriptyline plasma levels rise 2- to 4-fold. Both drugs are also serotonergic.
Symptoms
Serotonin syndrome (agitation, tremor, tachycardia). Amitriptyline anticholinergic effects (dry mouth, constipation, confusion in older patients). QT prolongation.
Management
If combined for augmentation, halve amitriptyline and check ECG at 2 weeks. Alternative: mirtazapine or agomelatine (no CYP2D6 dependence).
Sources
Mechanism
Sertraline (SSRI) depletes the platelet serotonin pool and impairs primary haemostasis. Combined with apixaban, upper GI bleeding risk roughly doubles.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
The combination is acceptable when antidepressant therapy is needed. PPI cover with pantoprazole is advisable. Alternative antidepressants with minimal platelet effect: mirtazapine or agomelatine.
Sources
Mechanism
Additive seizure threshold reduction. Sertraline is a weak CYP2D6 inhibitor with minimal effect on bupropion. Real risk is limited to patients with risk factors (prior epilepsy, eating disorders).
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
The combination is widely used for augmentation. Without risk factors, no special measures are needed. Standard doses. Avoid with prior epilepsy or eating disorders.
Mechanism
Two SSRIs simultaneously – serotonin syndrome without therapeutic rationale. Citalopram itself prolongs QT.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.
Management
The combination is not prescribed. When switching SSRIs, allow a 1-week washout. For augmentation: mirtazapine or agomelatine (different class).
Mechanism
Sertraline at high doses (above 150 mg/day) moderately prolongs QT. Combined with dronedarone, risk of torsades de pointes rises, especially in older patients.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination with sertraline above 100 mg. At low doses (50–100 mg) with normal potassium and magnesium, the combination is acceptable with ECG monitoring at 2 weeks. Alternative antidepressants: mirtazapine or agomelatine.
Mechanism
SSRI (sertraline) + SNRI (duloxetine) – additive serotonergic load, serotonin syndrome risk without therapeutic rationale.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
The combination is not prescribed. When switching antidepressants, allow a 1-week washout. For augmentation, use mirtazapine or agomelatine.
Mechanism
Two SSRIs simultaneously raise synaptic serotonin activity. Without added clinical benefit, additive effect raises serotonin syndrome, hyponatraemia, and GI bleeding risks.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
The combination is not prescribed. If one SSRI is ineffective, switch to another after a 2-week washout (or 5 weeks after fluoxetine). In severe depression, monotherapy plus mirtazapine or psychotherapy.
Mechanism
Sertraline at high doses prolongs QT, additively with haloperidol. Sertraline also weakly blocks CYP2D6, so haloperidol levels may rise.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination with sertraline above 100 mg and parenteral haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. Alternative antidepressants: mirtazapine or agomelatine.
Mechanism
St John's wort contains hypericin and hyperforin – serotonergic activators and strong inducers of CYP3A4 and P-glycoprotein. On sertraline (SSRI), serotonergic activity adds up; serotonin syndrome risk arises.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever above 38.5 °C.
Management
The combination is not prescribed. Warn the patient that St John's wort is not a neutral herbal supplement but an active serotonergic with dozens of drug interactions. CYP3A4 induction persists for 1–2 weeks after stopping the herb.
Mechanism
SSRI augmentation with mirtazapine in resistant depression is possible ('California rocket fuel'). Additive serotonergic effect is rare, but serotonin syndrome has been reported at high doses of both.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.
Management
The combination is used for antidepressant augmentation. Keep doses low: sertraline 100 mg, mirtazapine 30 mg/day. Monitor blood pressure and mental status in the early weeks.
Mechanism
Sertraline (SSRI) raises synaptic serotonin; tramadol blocks serotonin and norepinephrine reuptake. Combined action amplifies serotonergic transmission. Sertraline also blocks CYP2D6 (less than fluoxetine) – the tramadol activation route.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
Avoid the combination. For analgesia on sertraline, use paracetamol, an NSAID, or morphine/oxycodone. For chronic analgesic needs, gabapentin or pregabalin for neuropathic pain.
Sources
Mechanism
SSRI (sertraline) + SNRI (venlafaxine) – additive serotonergic load. The combination is not used in clinical practice.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
The combination is not prescribed. When switching antidepressants, allow a 1-week washout. For augmentation, add mirtazapine or agomelatine (different class).
Mechanism
Sertraline (SSRI) blocks serotonin reuptake into platelets, depleting the platelet serotonin pool and impairing primary haemostasis. Even with a stable INR, GI bleeding risk roughly doubles in warfarin-treated patients.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
The combination is acceptable. PPI cover with pantoprazole and more frequent INR checks (every 2–4 weeks in the first month) are advisable. Alternative antidepressants with minimal platelet effect: mirtazapine or agomelatine.
Sources
Mechanism
Additive QT prolongation (sertraline minimally prolongs QT at standard doses, azithromycin dose-dependently).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses (3–5 days) with sertraline ≤150 mg, the combination is acceptable. In cardiovascular disease: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).
Mechanism
Both prolong QT. In low-risk patients the effect is clinically minor; risk rises with hypokalaemia, hypomagnesaemia, bradycardia, and concurrent QT-prolonging drugs.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short ciprofloxacin courses (5–7 days) in young patients without cardiac disease, the combination is acceptable. In older patients, atrial fibrillation, hypokalaemia, or other QT-prolonging drugs: ECG before start, alternative antibiotics (cephalosporin, amoxicillin-clavulanate, doxycycline).
Mechanism
Clopidogrel blocks platelet aggregation via the P2Y12 receptor; sertraline impairs primary haemostasis by inhibiting platelet serotonin reuptake. Additive bleeding risk, mainly gastrointestinal.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
The combination is acceptable. In patients over 65 or with prior peptic ulcer disease, add gastroprotection — pantoprazole or esomeprazole 20 mg/day (avoid omeprazole — it suppresses clopidogrel activation). Antidepressant alternative without platelet effect: mirtazapine or agomelatine.
Sources
Mechanism
Both can cause hyponatraemia: furosemide via natriuresis, sertraline via SIADH-like mechanism. Additive risk, especially in older women with low body weight.
Symptoms
Headache, nausea, confusion, drowsiness; severe cases: seizures. Develops slowly over 1–2 weeks and is often missed in older patients.
Management
Check sodium 2 weeks after sertraline start, then every 6 months. If sodium falls below 130 mmol/L, switch sertraline to mirtazapine or agomelatine (do not cause hyponatraemia). In older patients with moderate hyponatraemia, fluid restriction to 1.5 L/day.
Sources
Mechanism
Thiazides are one of the most common drug causes of hyponatraemia in older patients via SIADH-like mechanism and natriuresis. SSRIs (sertraline) add a SIADH-like effect. Additive risk.
Symptoms
Headache, nausea, confusion, drowsiness; severe cases: seizures. Develops slowly over 1–2 weeks and is often missed in older patients.
Management
On the combination, check sodium at 2 and 4 weeks after starting sertraline or the thiazide, then every 6 months. If sodium falls below 130 mmol/L, consider switching sertraline to mirtazapine or agomelatine, or replacing the thiazide with indapamide (lower hyponatraemia risk).
Sources
Mechanism
Omeprazole inhibits CYP2C19, the enzyme responsible for sertraline metabolism. Sertraline levels rise by about 40%. Adverse effects may intensify: nausea, insomnia, sexual dysfunction.
Symptoms
Nausea, diarrhoea, insomnia or somnolence, tremor, anxiety, decreased libido. Symptoms appear in the first 1–2 weeks after starting omeprazole in patients on stable sertraline.
Management
For short omeprazole courses (2–4 weeks), no specific adjustment needed. For long-term therapy with significant adverse effects, reduce sertraline by 25–50% or switch to pantoprazole (minimal CYP2C19 effect).
Sources
Mechanism
Prednisolone is ulcerogenic — suppresses prostaglandin synthesis and gastric mucosal turnover. Sertraline reduces platelet aggregation via serotonin uptake. Additive GI bleeding risk.
Symptoms
Epigastric pain, heartburn, black or tarry stools, blood in vomit, bruising. Higher risk in older patients and prior peptic ulcer disease.
Management
On the combination, in patients over 65, with prior peptic ulcer, or on long-term prednisolone (over 2 weeks), add pantoprazole 20 mg/day. For short courses (3–7 days), additional gastroprotection is not mandatory.
Mechanism
Calcium carbonate and sertraline are metabolised by different pathways. No direct interaction.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. In women with depression and osteoporosis, the combination is standard.
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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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.