SSRI (selective serotonin reuptake inhibitors)

5-HT3 receptor antagonists, SSRI ---> SmPC of [granisetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Aceclofenac [1], SSRI ---> SmPC of [1] of eMC

Selective serotonin reuptake inhibitors (SSRIs) increase risk of gastrointestinal bleeding

Acemetacine, SSRI

The co-administration can increase the risk of gastrointestinal bleeding

Acenocoumarol [1], SSRI ---> SmPC of [1] of eMC

The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk

Acetylsalicylic acid, SSRI ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Alcohol, SSRI ---> SmPC of [fluoxetine] of eMC

In formal testing, fluoxetine did not raise blood alcohol levels or enhance the effects of alcohol. However, the combination of SSRI treatment and alcohol is not advisable.

Almotriptan [1], SSRI ---> SmPC of [1] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) and triptans

Amifampridine [1], SSRI ---> SmPC of [1] of EMA

The concomitant use of amifampridine and substances known to lower the epileptic threshold leads to an increased risk of seizures

Amitriptylinoxide, SSRI

The previous or concomitant treatment of SSRIs with amitriptylinoxide may increase the plasma levels of amitriptylinoxide, or its metabolites, by substrate competition

Antiepileptics, SSRI ---> SmPC of [ethosuximide] of eMC

The anticonvulsant effect of antiepileptic agents may be antagonized by SSRIs (convulsive threshold lowered)

Aripiprazole [1], SSRI ---> SmPC of [1] of EMA

Cases of serotonin syndrome have been reported in patients taking aripiprazole, and possible signs and symptoms for this condition can occur especially in cases of concomitant use with other serotonergic medicinal products

Atomoxetine, SSRI

Seizures are a potential risk with atomoxetine. Caution is advised with concomitant use of medicinal drugs which are known to lower the seizure threshold

Atypical neuroleptics, SSRI

There have been reports of bleeding abnormalities with SSRIs. Caution is advised in patients taking SSRIs, particularly in concomitant use with medicinal products known to affect platelet function

Bupropion [1], SSRI ---> SmPC of [1] of eMC

There is an increased risk of seizures occurring with the use of bupropion in the presence of predisposing risk factors which lower the seizure threshold.

Buspirone [1], SSRI ---> SmPC of [1] of eMC

The combination of buspirone and selective serotonin reuptake inhibitors (SSRI) was tested in a number of clinical trials. Although no severe toxicities were observed, there were rare cases of seizures

Butyrophenones, SSRI

Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Carbamazepine, SSRI

The co-administration may cause a toxic serotoninergic syndrome

Clomipramine [1], SSRI ---> SmPC of [1] of eMC

Serotonin Syndrome can possibly occur when clomipramine is administered with other serotonergic co-medications

Clopidogrel [1], SSRI ---> SmPC of [1] of EMA

Since SSRIs affect platelet activation and increase the risk of bleeding, the concomitant administration of SSRIs with clopidogrel should be undertaken with caution.

Clopidogrel/acetylsalicylic acid [1], SSRI ---> SmPC of [1] of EMA

Since SSRIs affect platelet activation and increase the risk of bleeding, the concomitant administration of SSRIs with clopidogrel should be undertaken with caution.

Cobicistat [1], SSRI ---> SmPC of [1] of EMA

Dose titration may be required for most medicinal products of the SSRI class, when co-administered with cobicistat.

Coxibs [1], SSRI ---> SmPC of [1] of eMC

Concomitant use of NSAIDs, including COX-2 selective inhibitors, and SSRIs increases the risk of gastrointestinal bleeding

Cyproheptadine [1], SSRI ---> SmPC of [1] of eMC

Drugs with anti-serotonin activity, such as cyproheptadine, may interfere with serotonin-enhancing anti-depressants including SSRI's. This may result in possible recurrence of depression and related symptoms.

Dapoxetine [1], SSRI ---> SmPC of [1] of eMC

Combination dapoxetine and serotonergic drugs (SD) may lead to incidence of serotonin associated effects. Dapoxetine should not be used with SD or in 14 d. of discontinuing SD. SD should not be given in 7 d. after discontinuing dapoxetine

Desmopressin [1], SSRI ---> SmPC of [1] of eMC

Substances which are known to induce SIADH may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

Dexibuprofen, SSRI

The co-administration can increase the risk of gastrointestinal bleeding

Dexketoprofen [1], SSRI ---> SmPC of [1] of eMC

The co-administration can increase the risk of gastrointestinal bleeding

Dextromethorphan, SSRI

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Dextromethorphan/quinidine [1], SSRI ---> SmPC of [1] of EMA

Caution should be exercised if patients are treated with concomitant selective serotonin reuptake inhibitors (SSRIs).

Diclofenac [1], SSRI ---> SmPC of [1] of eMC

lncreased risk of gastrointestinal bleeding

Dopamine antagonists, SSRI

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Droperidol, SSRI [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Duloxetine [1], SSRI ---> SmPC of [1] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if duloxetine is used concomitantly with serotonergic agents

Edoxaban [1], SSRI ---> SmPC of [1] of EMA

As with other anticoagulants the possibility may exist that patients are at increased risk of bleeding in case of concomitant use with SSRIs or SNRIs due to their reported effect on platelets

Eletriptan [1], SSRI ---> SmPC of [1] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, SSRI [2] ---> SmPC of [2] of EMA

Concentrations of antidepressant agents may be increased when co-administered with cobicistat. Careful dose titration of the antidepressant and monitoring for antidepressant response is recommended.

Ethosuximide, SSRI

The anticonvulsant effect of antiepileptic agents may be antagonized by SSRIs (convulsive threshold lowered)

Fenfluramine, SSRI

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Fentanyl [1], SSRI ---> SmPC of [1] of EMA

The concomitant use of fentanyl with a serotoninergic drug may increase the risk of serotoninergic syndrome, a life-threatening disorder

Fluphenazine, SSRI [2] ---> SmPC of [2] of eMC

There have been rare reports of acute Parkinsonism when an SSRI has been used in combination with a phenothiazine.

Flurbiprofen [1], SSRI ---> SmPC of [1] of eMC

The combination of selective serotonin reuptake inhibitors (SSRIs) and NSAIDs increases the risk of gastrointestinal bleeding

Fluvoxamine [1], SSRI ---> SmPC of [1] of eMC

The serotonergic effects of fluvoxamine may be enhanced when used in combination with other serotonergic agents

Frovatriptan [1], SSRI ---> SmPC of [1] of eMC

Selective serotonin-reuptake inhibitors mit frovatriptan: Potential risk of hypertension, coronary vasoconstriction or serotonin syndrome. Strict adherence to the recommended dose is an essential factor to prevent this syndrome.

Ibuprofen, SSRI

Increased risk of gastrointestinal bleeding

IMAOs, SSRI ---> SmPC of [fluoxetine] of eMC

Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with MAOI, and in patients who have recently discontinued an SSRI and have started on a MAOI.

Imipramine [1], SSRI ---> SmPC of [1] of eMC

Co-medication of SSRIs and imipramine may lead to additive effects on the serotonergic system.

Indometacin, SSRI

The co-administration may increase the risk of gastrointestinal bleeding

Insulin lispro [1], SSRI ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin, SSRI ---> SmPC of [escitalopram] of eMC

In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Irreversible non-selective MAO-inhibitors, SSRI

Cases of serious reactions have been reported in patients receiving an SSRI in combination with a non-selective irreversible MAOI, and in patients who have recently discontinued SSRI treatment and have been started on such MAOI treatment

Isocarboxazid [1], SSRI ---> SmPC of [1] of eMC

There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death) when serotonin reuptake inhibitors or serotonin/noradrenaline inhibitors (e.g. venlafaxine) have been combined with MAOIs.

Ketoprofen [1], SSRI ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Ketorolac [1], SSRI ---> SmPC of [1] of eMC

There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs.

Linezolid [1], SSRI ---> SmPC of [1] of eMC

During clinical use of linezolid with serotonergic agents cases of serotonin syndrome have been reported. Co-administration is contraindicated

Lithium, SSRI ---> SmPC of [fluoxetine] of eMC

There have been reports of serotonin syndrome when SSRIs have been given with lithium or tryptophan

Lofepramine, SSRI

Co-medication of lofepramine with SSRI inhibitors may lead to additive effects on the serotonergic system.

Lornoxicam, SSRI

The co-administration may increase the risk of gastrointestinal haemorrhage

Loxapine [1], SSRI ---> SmPC of [1] of EMA

Caution is advised if loxapine is combined with other medicinal products known to lower the seizure threshold

Maprotiline, SSRI

The CYP2D6 inhibition may increase the plasma levels of maprotiline. Dose adjustment may be necessary

Mefloquine, SSRI [2] ---> SmPC of [2] of eMC

Concomitant administration of mefloquine and drugs known to lower the epileptogenic threshold may increase the risk of convulsions

Meloxicam, SSRI

The co-administration may increase the risk of gastrointestinal haemorrhage

Methylphenidate, SSRI

Methylphenidate may inhibit the metabolism of selective serotonin reuptake inhibitors

Methylthioninium chloride, SSRI

Methylthioninium chloride should be avoided in patients receiving medicinal products that enhance serotonergic transmission

Methylthioninium [1], SSRI ---> SmPC of [1] of EMA

Methylthioninium should be avoided with medicinal products that enhance serotonergic transmission

Metoclopramide, SSRI

The co-administration may enhance the extrapyramidal symptoms until a serotoninergic syndrome

Mirtazapine [1], SSRI ---> SmPC of [1] of eMC

Co-administration of mirtazapine with other serotonergic active substances may lead to an incidence of serotonin associated effects (serotonin syndrome). Caution should be advised

Moclobemide, SSRI [2] ---> SmPC of [2] of eMC

Moclobemide should not be co-administered with 5-HT re-uptake inhibitors (including those which are tricyclic antidepressants) in order to prevent precipitation of serotonergic overactivity

Nabumetone [1], SSRI ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Naproxen [1], SSRI ---> SmPC of [1] of eMC

Selective serotonin reuptake inhibitors (SSRls) may increase the risk of gastrointestinal bleeding

Naproxen/esomeprazole [1], SSRI ---> SmPC of [1] of eMC

Concomitant use of NSAIDs, including COX-2 selective inhibitors, and SSRIs increases the risk of gastrointestinal bleeding

Naratriptan [1], SSRI ---> SmPC of [1] of eMC

Serotonin syndrome has been reported following concomitant treatment with triptans and SSRIs/SNRIs

Netupitant/palonosetron [1], SSRI ---> SmPC of [1] of EMA

There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic medicinal products

Neuroleptics, SSRI

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Nimesulide, SSRI

The co-administration may increase the risk of gastrointestinal haemorrhage or ulcera

Nortriptyline, SSRI

La co-administration of selective serotonin reuptake inhibitors may increase the plasma levels of nortriptyline. It may be necessary to decrease the dose

NSAID, SSRI ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Ondansetron [1], SSRI ---> SmPC of [1] of eMC

There have been post-marketing reports describing patients with serotonin syndrome following the concomitant use of ondansetron and other serotonergic drugs

Opipramol, SSRI

Serotonin Syndrome can possibly occur when opipramol is administered with other serotonergic co-medications

Oral anticoagulants, SSRI ---> SmPC of [paroxetine] of eMC

Caution is advised in patients taking SSRIs, concomitantly with oral anticoagulants, drugs known to affect platelet function or increase risk of bleeding

Oral antidiabetics, SSRI ---> SmPC of [escitalopram] of eMC

In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Paliperidone [1], SSRI ---> SmPC of [1] of EMA

Caution is advised if paliperidone is combined with other medicines known to lower the seizure threshold

Palonosetron [1], SSRI ---> SmPC of [1] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Paroxetine [1], SSRI ---> SmPC of [1] of eMC

As with other SSRIs, co-administration with serotonergic drugs may lead to an incidence of 5-HT associated effects (serotonin syndrome)

Perphenazine, SSRI

Concomitant use of perphenazine with drugs inhibiting the metabolism of perphenazine is not recommended.

Pethidine, SSRI

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Phenelzine [1], SSRI ---> SmPC of [1] of eMC

There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death) when serotonin reuptake inhibitors or serotonin/noradrenaline inhibitors (e.g. venlafaxine) have been combined with MAOIs.

Phenindione, SSRI

The co-administration is not recommended since it may increase the intensity of bleedings

Phenobarbital, SSRI [2] ---> SmPC of [2] of eMC

Antidepressants may antagonise the antiepileptic activity of phenobarbital by lowering the convulsive threshold

Phenothiazines, SSRI ---> SmPC of [fluphenazine] of eMC

There have been rare reports of acute Parkinsonism when an SSRI has been used in combination with a phenothiazine.

Phenprocoumon, SSRI

The co-administration may enhance the anticoagulant effect and increase the bleeding risk

Phenylbutazone, SSRI

Increased risk of gastrointestinal bleedings

Pimozide [1], SSRI ---> SmPC of [1] of eMC

Pimozide is contraindicated with concomitant use of serotonin uptake inhibitors

Piroxicam [1], SSRI ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Platelet aggregation inhibitors, SSRI ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Pregnancy, SSRI

The use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn

Primidone, SSRI

Primidone, enzymatic inductor, may accelerate the metabolism of SSRI and decrease its plasma levels and effect

Proglumetacine, SSRI

The co-administration may increase the risk of gastrointestinal haemorrhage

Propafenone, SSRI

Elevated levels of plasma propafenone may occur when propafenone is used concomitantly with selective serotonin reuptake inhibitors. Lower doses of propafenone may be sufficient to achieve the desired therapeutic response.

Rasagiline [1], SSRI ---> SmPC of [1] of EMA

In the post-marketing period, cases of serotonin syndrome associated with agitation, confusion, rigidity, pyrexia and myoclonus have been reported by patients treated with antidepressants/SNRI concomitantly with rasagiline.

Rivaroxaban [1], SSRI ---> SmPC of [1] of EMA

As with other anticoagulants the possibility may exist that patients are at increased risk of bleeding in case of concomitant use with SSRIs or SNRIs due to their reported effect on platelets.

Rizatriptan [1], SSRI ---> SmPC of [1] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) and triptans.

Safinamide [1], SSRI ---> SmPC of [1] of EMA

Serious adverse reactions have been reported with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and MAO inhibitors

Seizure-threshold lowering drugs, SSRI ---> SmPC of [escitalopram] of eMC

SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Selegiline [1], SSRI ---> SmPC of [1] of eMC

Because of the risk of confusion, hypomania, hallucination and manic episodes, agitation, myoclonus, hyperreflexia, etc., which can be part of the serotonin syndrome, concomitant administration of selegiline and SSRIs is contraindicated.

Serotonergic medicines, SSRI ---> SmPC of [duloxetine] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable

Serotonin agonists, SSRI

Potential risk of a serotoninergic syndrome

Serotonin antagonists [1], SSRI ---> SmPC of [1] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Sibutramine [1], SSRI ---> SmPC of [1] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

SSRI, St. John's wort

Dynamic interactions between SSRI and the herbal remedy St John's wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects

SSRI, sumatriptan [2] ---> SmPC of [2] of eMC

There have been rare post-marketing reports describing patients with serotonin syndrome following the use of SSRIs and sumatriptan.

SSRI, tapentadol [2] ---> SmPC of [2] of eMC

In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotoninergic medicinal products

SSRI, tenoxicam

The co-administration may increase the risk of gastrointestinal haemorrhage or ulcera

SSRI, thioxanthenes

Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

SSRI, tiaprofenic acid

Increased risk of gastrointestinal bleeding.

SSRI, ticagrelor [2] ---> SmPC of [2] of EMA

Due to reports of cutaneous bleeding abnormalities with SSRIs, caution is advised when administering SSRIs with ticagrelor as this may increase the risk of bleeding.

SSRI, ticlopidine ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

SSRI, timolol

The CYP2D6 inhibition may increase plasma concentrations of timolol

SSRI, tramadol [2] ---> SmPC of [2] of eMC

Tramadol can induce convulsions and increase the potential of other seizure threshold-lowering medicinal products to cause convulsions. Concomitant therapeutic use of tramadol and serotonergic drugs may cause serotonin toxicity.

SSRI, tranylcypromine

Tranylcypromine should not be used together with drugs with marked serotonin-reuptake inhibition. Risk of serotonin syndrome with symptoms like hypertension, irritability, hyperthermia with possible fatal outcome

SSRI, trazodone [2] ---> SmPC of [2] of eMC

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of trazodone and other serotonergically acting substances

SSRI, tricyclic antidepressant

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

SSRI, trimipramine

The previous or concomitant treatment of SSRIs with trimipramine may increase the plasma levels of both antidepressants by substrate competition

SSRI, triptans ---> SmPC of [almotriptan] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) and triptans

SSRI, tryptophan ---> SmPC of [fluoxetine] of eMC

There have been reports of serotonin syndrome when SSRIs have been given with lithium or tryptophan

SSRI, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

SSRI, vorapaxar [2] ---> SmPC of [2] of EMA

The use of certain concomitant medicinal products (e.g., selective serotonin reuptake inhibitors) may increase the risk of bleeding in patients taking vorapaxar.

SSRI, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

SSRI, ziprasidone

Risk of serotonin syndrome

SSRI, zolmitriptan [2] ---> SmPC of [2] of eMC

There have been isolated reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) and triptans