Selective serotonin reuptake inhibitors (SSRIs)
Brand names: Zoloft
Updated · Methodology
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
ICD-10: F41.1 · ICD-11: 6B00
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.
Sources
ICD-10: F32.9 · ICD-11: 6A70.Z
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
ICD-10: F42 · ICD-11: 6B20
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
ICD-10: F41.0 · ICD-11: 6B01
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.
Sources
ICD-10: F43.1 · ICD-11: 6B40
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.
ICD-10: F41.9 · ICD-11: 6B0Z
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.
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.
AEMPS summary of product characteristics (section 4.6): there are no well-controlled studies in pregnant women, but a large body of data shows no congenital malformations linked to sertraline. Sertraline is not recommended in pregnancy unless the expected benefit for the mother outweighs the potential risk. After use late in pregnancy, some newborns develop withdrawal or serotonergic symptoms (respiratory distress, cyanosis, seizures, unstable temperature, feeding problems, hypoglycaemia, irritability), usually within 24 hours of birth. SSRI use late in pregnancy may increase the risk of persistent pulmonary hypertension of the newborn (about 5 per 1,000 pregnancies versus 1–2 per 1,000 in the general population), and use in the month before delivery raises the risk of postpartum haemorrhage (less than twofold).
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.
In a study of eight healthy volunteers cited in the Besitran SmPC, three glasses of grapefruit juice a day roughly doubled sertraline levels. More sertraline means more nausea, diarrhoea, tremor, insomnia or drowsiness, and with other serotonergic drugs a higher risk of serotonin syndrome (agitation, sweating, fever, rigidity). The SmPC does not recommend grapefruit juice during treatment.
Source: AEMPS: Ficha técnica de Besitran 50 mg comprimidos recubiertos con película (sertralina) (2025)
31 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
Mechanism
Methylene blue (methylthioninium chloride) inhibits monoamine oxidase (MAO). The US Food and Drug Administration () sertraline label classes intravenous methylene blue as an MAO inhibitor, and the FDA methylene blue label cites literature describing it as a potent reversible inhibitor of this enzyme. Sertraline blocks serotonin reuptake. Together they can cause severe, sometimes fatal serotonin syndrome (methylene blue labels). The Spanish sertraline SmPC reports serious reactions, including deaths, also when sertraline was started soon after stopping an MAO inhibitor such as methylene blue, or an MAO inhibitor was started right after stopping sertraline. No reports involved other routes of methylene blue, such as oral tablets or local tissue injection (FDA sertraline label).
Symptoms
Serotonin syndrome. Mental status changes: agitation, hallucinations, delirium, coma. Autonomic signs: tachycardia, labile blood pressure, dizziness, sweating, flushing, fever. Neuromuscular signs: tremor, rigidity, myoclonus, hyperreflexia, incoordination. Seizures, nausea, vomiting and diarrhoea may occur. Some reported cases were fatal ( methylene blue label).
Management
The combination is contraindicated: the US Food and Drug Administration () sertraline label contraindicates sertraline in patients taking MAO inhibitors, including intravenous methylene blue, or within 14 days of stopping them. The methylene blue labels approved by the European Medicines Agency () and the FDA say to avoid it in patients taking selective serotonin reuptake inhibitors. If a patient on sertraline needs methylene blue, stop sertraline before it is given (FDA sertraline label). When methylene blue cannot be avoided, give the lowest possible dose and observe the patient for nervous system effects for 4 hours (methylene blue labels). Monitor the ECG and blood pressure during and after the infusion (EMA methylene blue SmPC). If signs of serotonin syndrome appear, stop methylene blue and sertraline and start supportive treatment (FDA labels of both drugs). Restart sertraline no earlier than 14 days after the last methylene blue dose (FDA sertraline label).
Sources
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.
Sources
Mechanism
Sertraline raises pimozide concentrations. With a single 2 mg dose of pimozide on top of sertraline 200 mg/day at steady state, pimozide AUC and Cmax rose by about 40% (pimozide label Orap, 4.5; Zoloft label, 12.3). The sertraline label quotes about 35% (4.5). The mechanism is unknown (sertraline label, 4.5). The pimozide label suggests that serotonin reuptake inhibitors may inhibit its CYP2D6 metabolism and names paroxetine and fluoxetine (Orap, 4.5). Pimozide has a narrow therapeutic index, and higher concentrations raise the risk of QTc prolongation and ventricular arrhythmias (Zoloft label, 7.1). Sertraline itself prolongs QTc in a concentration-dependent way (sertraline label, 4.4; Zoloft, 5.10), so the pharmacodynamic effect on repolarisation comes on top of the kinetic interaction. Pimozide doses above 2 mg have not been studied with sertraline (Zoloft, 12.3).
Symptoms
QTc prolongation on the ECG, T-wave changes and U waves (pimozide label), torsade de pointes, ventricular arrhythmias, sudden death. The patient experiences palpitations, dizziness or syncope. With pimozide 2 mg the study showed no ECG change, but there are no data for higher doses (Zoloft, 12.3). The risk is higher with hypokalaemia and hypomagnesaemia, bradycardia, heart disease and a family history of QT prolongation (sertraline label, 4.4). It is also higher in CYP2D6 poor metabolisers, 5–10% of the population, whose pimozide concentrations match those seen with strong inhibitors (Orap, 4.4).
Management
The combination is contraindicated from both sides. The AEMPS sertraline label (4.3) bars use with pimozide outright, and the AEMPS pimozide label (Orap, 4.3) bars pimozide with serotonin reuptake inhibitors and names sertraline. The labels say the same: sertraline is contraindicated in patients taking pimozide (Zoloft, section 4), and pimozide is contraindicated in patients on sertraline (Contraindications). If a patient is already on both, the combination is stopped and an ECG is recorded. Another drug of the same class is not an automatic replacement. The pimozide label also contraindicates paroxetine, citalopram and escitalopram (Orap, 4.3) and names fluoxetine as a CYP2D6 inhibitor (Orap, 4.5); the FDA label says to avoid fluvoxamine as a CYP3A4 inhibitor and reports bradycardia with fluoxetine. Pimozide needs an ECG before the start and periodically during treatment, and is stopped at QT or QTc above 500 ms (Orap, 4.4). Hypokalaemia and hypomagnesaemia are contraindications for it (Orap, 4.3); potassium is corrected before the start and kept normal (FDA label). Sertraline is used with caution in patients with risk factors for QTc prolongation (sertraline label, 4.4; Zoloft, 5.10).
Sources
Mechanism
Selegiline irreversibly inhibits monoamine oxidase (MAO), the enzyme that breaks down catecholamines and serotonin. At recommended doses it acts mainly on MAO type B (MAO-B) and loses this selectivity above 10 mg a day (selegiline SmPC; US Food and Drug Administration () selegiline label). Sertraline is a selective serotonin reuptake inhibitor: it stops nerve endings from taking serotonin back up. Selegiline slows serotonin breakdown, so serotonin builds up and serotonin syndrome can follow (sertraline SmPC, section 4.3; FDA sertraline label). Severe reactions have occurred even at the usual selegiline dose of 10 mg a day combined with sertraline, fluoxetine or paroxetine, and their mechanism is not fully understood (FDA selegiline label). Selegiline appears among the irreversible MAO inhibitors in the sertraline summary of product characteristics. The waiting times for this group therefore apply when switching between the two drugs (sertraline SmPC, section 4.5).
Symptoms
Combining selegiline with selective serotonin reuptake inhibitors, the class sertraline belongs to, can cause confusion, hypomania, hallucinations and manic episodes, agitation, myoclonus, hyperreflexia, incoordination, shivering, tremor, seizures, ataxia, sweating, diarrhoea, fever and hypertension, all of which can be part of serotonin syndrome (selegiline SmPC, section 4.5). Patients who started sertraline soon after stopping a monoamine oxidase inhibitor, or the other way round, have had tremor, myoclonus, sweating, nausea, vomiting, flushing, dizziness, hyperthermia resembling neuroleptic malignant syndrome and seizures, and some cases were fatal (sertraline SmPC, section 4.5). Tachycardia, labile blood pressure, muscle rigidity, delirium and coma can also occur (US Food and Drug Administration () sertraline label).
Management
The combination is contraindicated (selegiline SmPC, sections 4.3 and 4.5; sertraline SmPC, sections 4.3 and 4.5, which give selegiline as an example; US Food and Drug Administration () sertraline label, section 4 and the table in section 7.1). Start sertraline no earlier than 14 days after stopping selegiline (sertraline SmPC, section 4.3; FDA sertraline and selegiline labels). When switching the other way, stop sertraline at least 7 days before the first dose of selegiline (sertraline SmPC, section 4.3). If a patient is already taking both, stop sertraline and selegiline immediately at the first signs of serotonin syndrome and start supportive symptomatic treatment (FDA sertraline label, section 5.2).
Sources
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
Both drugs prolong the QT interval. Sertraline does so in a concentration-dependent way: at twice the maximum recommended dose the largest mean increase was 10 ms (sertraline label of the US Food and Drug Administration, ). Azithromycin, like other macrolides, prolongs cardiac repolarisation and the QT interval, which carries a risk of torsades de pointes (azithromycin SmPC). The effects add up.
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
The US Food and Drug Administration () label of sertraline says to avoid drugs known to prolong the QT interval; its examples include antibiotics such as the macrolide erythromycin (sertraline FDA label). The US azithromycin label asks prescribers to weigh the risk of QT prolongation in patients who already take such drugs (azithromycin FDA label). European SmPCs allow the combination with caution: azithromycin is used carefully in patients with QT prolongation, low potassium or magnesium, clinically relevant bradycardia, arrhythmia, severe heart failure and in older people, and sertraline in heart disease, low potassium or magnesium, a family history of QT prolongation and bradycardia (azithromycin and sertraline SmPCs). Avoid the combination where possible; if azithromycin is still needed, assess these risk factors before starting.
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.
Sources
Mechanism
Both drugs prolong the QT interval. Sertraline does so in a concentration-dependent way: at twice the maximum recommended dose the largest mean increase was 10 ms (sertraline label of the US Food and Drug Administration, ). Ciprofloxacin, like other fluoroquinolones, prolongs the QT interval; ventricular arrhythmias and torsades de pointes have been reported with it, mostly in patients with risk factors (ciprofloxacin SmPC). The effects add up; the risk is higher with congenital long QT, low potassium or magnesium, heart disease, bradycardia, in older people and in women (ciprofloxacin and sertraline SmPCs).
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
The US Food and Drug Administration () label of sertraline says to avoid drugs known to prolong the QT interval; its examples include antibiotics, among them fluoroquinolones (sertraline FDA label). European SmPCs are softer and allow the combination with caution: sertraline and ciprofloxacin are used carefully in patients with risk factors for QT prolongation, such as congenital long QT, low potassium or magnesium, heart disease or bradycardia, and ciprofloxacin also in older people and women (sertraline and ciprofloxacin SmPCs). Avoid the combination where possible; if ciprofloxacin is still needed, assess these risk factors before starting.
Sources
Mechanism
Sertraline belongs to the same class. Its SmPC states outright that the risk of serotonin syndrome and neuroleptic malignant syndrome rises with concomitant serotonergic drugs, other antidepressants included. Post-marketing reports also describe QTc prolongation with torsade, mostly in patients with other risk factors.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.
Management
Two SSRIs together add no effect while their risks stack. Most often the pair is the trace of an unfinished switch, and one drug stays in the regimen.
Sources
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.
Sources
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
Sertraline belongs to the same class. Its SmPC states outright that the risk of serotonin syndrome and neuroleptic malignant syndrome rises with concomitant serotonergic drugs, other antidepressants included. Post-marketing reports also describe QTc prolongation with torsade, mostly in patients with other risk factors.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.
Management
Two SSRIs together add no effect while their risks stack. Most often the pair is the trace of an unfinished switch, and one drug stays in the regimen.
Sources
Mechanism
These are two SSRIs, so serotonergic load doubles with no proven therapeutic gain. The sertraline label bars combining it with other serotonergic agents such as moclobemide precisely because of serotonin syndrome risk. A pharmacokinetic issue is added: fluoxetine inhibits CYP2D6 and its active metabolite persists for weeks, so the overlap continues long after the last capsule.
Symptoms
Agitation, tremor, sweating, dilated pupils, diarrhoea, tachycardia, muscle rigidity and fever: serotonin syndrome develops within hours. Mild forms are mistaken for anxiety or flu. At high doses QT prolongation adds to the risk.
Management
The two SSRIs are not taken together. Switching from fluoxetine to sertraline needs a washout because of the long half-life of the active metabolite; the reverse switch allows shorter gaps. If tremor, sweating and tachycardia appear after the second drug is added, stop the addition.
Sources
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.
Sources
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.
Sources
Mechanism
SSRIs reduce platelet serotonin uptake – impaired aggregation. With NSAIDs (antiplatelet + GI mucosal damage) – significant GI bleeding risk increase.
Symptoms
GI bleeding, especially in patients over 60 with prior peptic ulcer disease.
Management
In high-risk patients – PPI gastroprotection. Alternative analgesic – paracetamol.
Sources
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.
Sources
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
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
Theoretical serotonin syndrome risk with SSRI + triptan. revised the recommendation in 2018 (previously CONTRA) – clinical cases at standard doses are few. Still, monitoring is needed at first use.
Symptoms
Rarely – agitation, tremor, myoclonus. Mainly with high triptan doses or SNRI combination.
Management
The AEMPS label for sertraline describes rare postmarketing cases of weakness, hyperreflexia and confusion, without banning the pair. Acceptable at standard doses. Inform patient of possible symptoms.
Sources
Mechanism
Sertraline, like other selective serotonin reuptake inhibitors (SSRIs), alters platelet function and raises bleeding risk on its own, from bruising and nosebleeds to life-threatening haemorrhage (US sertraline label, ). With warfarin these risks add up (US sertraline label). Sertraline 200 mg a day also produced a small but statistically significant increase in prothrombin time, which in rare cases can change the international normalised ratio (INR) (sertraline SmPC).
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 with monitoring. Check prothrombin time (international normalised ratio, INR) carefully when sertraline is started or stopped (sertraline SmPC). The US Food and Drug Administration () also advises careful INR monitoring in patients on warfarin (US sertraline label) and close monitoring for signs of bleeding (US warfarin label). Take particular care in patients with a history of bleeding disorders (sertraline SmPC). Warn the patient about the higher bleeding risk and ask them to mention any over-the-counter medicines that add to it, such as aspirin and non-steroidal anti-inflammatory drugs (US sertraline label).
Sources
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.
Verbatim lines from the interaction sections, in the language of the label
«Inhibidores de la monoaminooxidasa (IMAOs) IMAOs irreversibles (ej. selegilina): Sertralina no se puede utilizar en combinación con IMAOs irreversibles tales como la selegilina. No debe iniciarse el…»AEMPS, section 4.5 · Open on CIMA
«IMAO reversible no selectivo (linezolid): El antibiótico linezolid es un IMAO reversible y no selectivo débil y no se debe utilizar en pacientes que estén siendo tratados con sertralina (ver sección…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [ See Warnings and…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [ See Warnings and…»FDA, section 4 · Open on DailyMed
«Inhibidor reversible selectivo de la MAO-A (moclobemida): Debido al riesgo de síndrome serotoninérgico, no debe administrarse sertralina en combinación con un IMAO reversible y selectivo, como la…»AEMPS, section 4.5 · Open on CIMA
«Pimozida: En un estudio de dosis única con una dosis baja de pimozida (2 mg), se ha observado un aumento de los niveles de pimozida de aproximadamente un 35%. Este incremento en los niveles no se ha…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: Taking pimozide [ See Drug Interactions ( 7.1 ) ].»FDA, section 4 · Open on DailyMed
«Inhibidores de la monoaminooxidasa (IMAOs) IMAOs irreversibles (ej. selegilina): Sertralina no se puede utilizar en combinación con IMAOs irreversibles tales como la selegilina. No debe iniciarse el…»AEMPS, section 4.5 · Open on CIMA
«Clinically Significant Drug Interactions: Examples: selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue»FDA, section 7 · Open on DailyMed
«Clinically Significant Drug Interactions: In tervention: Pimozide is contraindicated for use with sertraline. Avoid the concomitant use of drugs known to prolong the QTc interval.»FDA, section 7 · Open on DailyMed
«Sangrado anormal/AEMPS, section 4.4 · Open on CIMA
«Sangrado anormal/AEMPS, section 4.4 · Open on CIMA
«Sangrado anormal/AEMPS, section 4.4 · Open on CIMA
«Clinically Significant Drug Interactions: Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents and…»FDA, section 7 · Open on DailyMed
«Sangrado anormal/AEMPS, section 4.4 · Open on CIMA
«Diabetes: En pacientes con diabetes, el tratamiento con un ISRS puede alterar el control glucémico. Puede ser necesario el ajuste de dosis de insulina y/AEMPS, section 4.4 · Open on CIMA
«Clinically Significant Drug Interactions: Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents and…»FDA, section 7 · Open on DailyMed
«Medicamentos que prolongan el intervalo QT: El riesgo de prolongación del QTc y/AEMPS, section 4.5 · Open on CIMA
«Hiponatremia: También pueden tener un mayor riesgo los pacientes que toman diuréticos o aquellos que por otras circunstancias tienen un menor volumen intravascular (ver Uso en pacientes de edad…»AEMPS, section 4.4 · Open on CIMA
«Se recomienda tener precaución con el uso de fentanilo (utilizado en anestesia general o en el tratamiento del dolor crónico), otros medicamentos serotoninérgicos (incluyendo otros antidepresivos…»AEMPS, section 4.5 · Open on CIMA
«Fenitoína: Además, la administración conjunta de fenitoína puede causar una disminución en los niveles plasmáticos de sertralina. No se puede excluir que otros inductores del CYP3A4, como por…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos metabolizados por el citocromo P450: La ingesta de inhibidores potentes del CYP3A4 se debe evitar durante el tratamiento con sertralina.»AEMPS, section 4.5 · Open on CIMA
«Diabetes: En pacientes con diabetes, el tratamiento con un ISRS puede alterar el control glucémico. Puede ser necesario el ajuste de dosis de insulina y/AEMPS, section 4.4 · Open on CIMA
«Diabetes: En pacientes con diabetes, el tratamiento con un ISRS puede alterar el control glucémico. Puede ser necesario el ajuste de dosis de insulina y/AEMPS, section 4.4 · Open on CIMA
«Litio: En un estudio controlado con placebo en voluntarios sanos, la administración conjunta de sertralina y litio no alteró significativamente la farmacocinética del litio, pero dio como resultado…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que prolongan el intervalo QT: El riesgo de prolongación del QTc y/AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death) when serotoninergic drugs (e.g., dexfenfluramine, fluoxetine…»FDA, section 4 · Open on DailyMed
«Está contraindicado el uso concomitante de Orap/AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Concomitant use of pimozide in patients taking sertraline is contraindicated (See PRECAUTIONS – Drug Interactions ).»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: • EMSAM (selegiline transdermal system) is contraindicated with selective serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine, sertraline, and paroxetine); serotonin and…»FDA, section 4 · Open on DailyMed
«DRUG INTERACTIONS: • CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: Antidepressants : Selective Serotonin Reuptake Inhibitors (SSRIs): paroxetine, sertraline Tricyclic Antidepressants (TCAs)…»FDA, section 7 · Open on DailyMed
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«Precauciones que incluyen ajuste de dosis: La administración concomitante de sustancias conocidas como inhibidores de la actividad de algunos de los isoenzimas del citocromo P450 puede aumentar los…»AEMPS, section 4.5 · Open on CIMA
«Potential for Other Drugs to Affect Clozapine: Concomitant treatment with clozapine and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine…»FDA, section 7 · Open on DailyMed
«ANTIDEPRESIVOS: Paroxetina 20 mg una vez al día Sertralina 50 mg una vez al día Amitriptilina Desipramina Imipramina Nortriptilina Trazodona»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: Antidepressant: Bupropion Sertraline ↓bupropion* ↓ sertraline * Increases in bupropion dosage should be guided by clinical response…»FDA, section 7 · Open on DailyMed
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que pueden aumentar las concentraciones plasmáticas de haloperidol: Inhibidores de la CYP2D6: bupropión, clorpromazina, duloxetina, paroxetina, prometazina, sertralina, venlafaxina.»AEMPS, section 4.5 · Open on CIMA
«Inducción farmacocinética de enzimas metabolizantes: La administración conjunta de metamizol con bupropión, efavirenz, metadona, valproato, ciclosporina, tacrólimus o sertralina puede disminuir los…»AEMPS, section 4.5 · Open on CIMA
Showing 40 of 124, heaviest first
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sertraline is evaluated for the following indications with varying evidence strength: Post-traumatic stress disorder (evidence tier A), Obsessive-compulsive disorder (evidence tier A), Generalized anxiety 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.
AEMPS summary of product characteristics (section 4.6): there are no well-controlled studies in pregnant women, but a large body of data shows no congenital malformations linked to sertraline. Sertraline is not recommended in pregnancy unless the expected benefit for the mother outweighs the potential risk. After use late in pregnancy, some newborns develop withdrawal or serotonergic symptoms (respiratory distress, cyanosis, seizures, unstable temperature, feeding problems, hypoglycaemia, irritability), usually within 24 hours of birth. SSRI use late in pregnancy may increase the risk of persistent pulmonary hypertension of the newborn (about 5 per 1,000 pregnancies versus 1–2 per 1,000 in the general population), and use in the month before delivery raises the risk of postpartum haemorrhage (less than twofold).
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.
Direct links to regulator labels. Open in a new tab.
Tranylcypromine, Trazodone, Venlafaxine, Vinpocetine, Amitriptyline, Duloxetine, Huperzine A (Huperzia serrata), Phenelzine