Selective serotonin reuptake inhibitors (SSRIs) learning module - main section

4.16 Important drug interactions

SSRIs inhibit the activity of cytochrome P450 isoenzymes but the inhibitory effect on different isoforms varies between individual members of the class. Important interactions of SSRIs involve enhancement of serotonergic activity, which, in rare cases, could result in the serotonin syndrome.

Consult summaries of product characteristics and other sources for information on the interactions of individual SSRIs

Interacting drug Effect of interaction Risk-reduction measures
Other antidepressants—including duloxetine; MAOIs (including moclobemide [specific for MAO-A] and older mixed MAO-A/B inhibitors such as phenelzine); St John’s wort; agomelatine; tricyclic antidepressants; tryptophan Increased serotonergic effect Avoid concomitant use (except under specialist supervision)—allow sufficient time for one drug to clear before starting another
Anticoagulants (including warfarin) Increased anticoagulant effect If SSRI needs to be continued, monitor INR closely during initiation of SSRI treatment and with any SSRI dose adjustment
Antiepileptics Convulsive threshold lowered  
Antimigraine drugs - 5HT1 receptor agonists (‘triptans’) Increased risk of serotonergic effects Avoid concomitant use
Antiplatelet drugs (including aspirin, clopidogrel, dipyridamole, ticlopidine) Increased risk of gastrointestinal bleeding If possible, avoid concomitant use; otherwise, also prescribe a gastroprotective medicine (such as a proton pump inhibitor or a histamine H2 antagonist
Linezolid Increased serotonergic effect Avoid concomitant use (except under specialist supervision) - allow sufficient time for one drug to clear before starting another
Lithium Increased risk of lithium toxicity  
Monoamine oxidase B inhibitors (rasagiline, selegiline) Increased risk of serotonergic effects Avoid concomitant use—allow sufficient time for one drug to clear before starting another
NSAIDs Increased risk of gastrointestinal bleeding If possible, avoid concomitant use; otherwise, also prescribe a gastroprotective medicine (such as a proton pump inhibitor or a histamine H2 antagonist
Pimozide Increased risk of ventricular arrhythmias Avoid concomitant use
Tamoxifen Inhibition of isoenzyme CYP2D6 by fluoxetine or paroxetine can reduce conversion of tamoxifen to active metabolites, thereby reducing anti-oestrogenic effect in breast cancer Avoid concomitant use of either fluoxetine or paroxetine with tamoxifen
Tramadol Increased risk of CNS toxicity (convulsions, serotonin syndrome)  

Page 21 of 29

Page last modified: 17 February 2015