4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. The following drug-drug interactions summarized in Table 6 are considered clinically relevant for SSRI antidepressants. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| fluoxetine | ergot derivatives | increased risk of ergotism due to fluoxetine inhibition of CYP3A4-mediated ergot metabolism | avoid concurrent use | moderate (CP) |
| SSRIs | anticoagulants | co-administration may increase bleeding risk due to impaired platelet aggregation most likely resulting from platelet serotonin depletion | patients should be monitored for signs/symptoms of bleeding (including INR) if combined therapy necessary | major (DrugReax) 3-moderate (CP) |
| SSRIs | drugs with serotonergic properties (e.g., antipsychotics, tramadol, triptans) or dopamine antagonist properties (e.g., phenothiazines, metoclopramide) | combined use may increase risk of serotonin syndrome or neuroleptic malignant syndrome (NMS) | cautiously administer concurrently and closely observe for signs/symptoms of serotonin syndrome or NMS, especially with treatment initiation or dosage increases | moderate(CP) |
| SSRIs | MAOIs | increased risk of serotonin syndrome (e.g., mental status changes, hyperpyrexia, autonomic instability, neuromuscular symptoms, seizures and/or gastrointestinal symptoms, restless, shivering, hypertonia, tremor) due to serotonin metabolism inhibition by monoamine oxidase | allow 14 days after MAOI discontinuation before initiating other antidepressant therapy; wait 5 weeks after discontinuing fluoxetine before initiating MAOIs | contraindicated (CP) |
| SSRIs | tramadol | increased risk of serotonin syndrome and seizures due to increased nervous system serotonin concentrations (additive effects on serotonin, SSRI inhibition of CYP2D6-mediated tramadol metabolism) as well as potential reduced seizure threshold with SNRIs, SSRIs | avoid concurrent use | moderate (CP) |
| SSRIs | pimozide | increased risk of pimozide toxicity including cardiotoxicity (QT prolongation) due to elevated plasma concentrations or additive effects on QT interval | avoid concurrent use | contraindicated (DrugReax) 1-severe (CP) |
| SSRIs | select phenothiazines (mesoridazine, thioridazine) | increased risk of somnolence, bradycardia and serious cardiotoxicity (QT prolongation, torsades de pointes) due to potential additive effects on QT interval prolongation; increased thioridazine serum concentrations/ decreased thioridazine elimination and potential for serious cardiac arrhythmias due to CYP2D6 inhibition by duloxetine, fluoxetine, or paroxetine | avoid concurrent use; if adjunctive use necessary, monitor for increased pharmacologic/toxic effects; adjust dose as necessary | contraindicated (CP) |
| Citalopram, Escitalopram | Chlorpromazine | Increased risk of QT prolongation and torsade’s de pointes. SSRIs may increase serum concentration of chlorpromazine leading to phenothiazine related reactions. Increased risk for serotonin syndrome. | Avoid concurrent use. If adjunctive use is necessary, ECG monitoring is recommended. Monitor for increased pharmacologic/toxic effects; adjust dose as necessary | Major (CP) |
| SSRI | Chlorpromazine | Increased risk of QT prolongation and torsade’s de pointes. SSRIs may increase serum concentration of chlorpromazine leading to phenothiazine related reactions. Increased risk for serotonin syndrome. | Should be avoided if possible. If adjunctive use is necessary, ECG monitoring is recommended. Monitor for increased pharmacologic/toxic effects; adjust dose as necessary | Major (CP) |
Legend:
- MAOI = monoamine oxidase inhibitor
- SNRI = serotonin-norepinephrine reuptake inhibitor
- SSRI= selective serotonin reuptake inhibitor
- # CP = Clinical Pharmacology