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