Selective serotonin reuptake inhibitors (SSRIs) are commonly used psychotropic medications to treat depression and anxiety. It is important to be aware of common drug interactions between them and other medications, especially because some SSRIs are competitive inhibitors of a variety of cytochrome P450 liver enzymes. Therefore, they can dramatically increase the blood levels of medications that are metabolized by those liver enzymes, which include various psychotropic medications as well as other medications commonly prescribed by primary care providers.
Fluoxetine and paroxetine are potent inhibitors of cytochrome CYP2D6. Here is a partial list of affected medications:
Psychotropic Medications Other Medications
Atypical antipsychotics Tramadol (increased risk of seizures)
Typical antipsychotics Codeine-based pain medications
Tricyclic antidepressants Dextromethorphan
Trazodone Beta blockers
Benztropine Diltiazem
Donepezil Odansetron
Venlafaxine Tamoxifen
Antiarrhythmic medications
With the drug interaction between fluoxetine and paroxetine and codeine-based pain medications, patients can experience reduced pain relief because the CYP2D6 inhibition will reduce conversion of codeine and related medications (hydrocodone, oxycodone) to the clinically effective metabolite (morphine, hydromorphone, oxymorphone).
Fluoxetine and fluvoxamine are potent inhibitors of cytochrome CYP2C19 (fluvoxamine more so than fluoxetine). Sertraline is a modest inhibitor of this enzyme. Here is a partial list of affected medications:
Psychotropic Medications Other Medications
Tricyclic antidepressants Proton pump inhibitors (ex. Omeprazole)
Diazepam Proguanil
Propranolol
Fluvoxamine is a fairly strong inhibitor of cytochrome CYP3A4. Here is a partial list of affected medications:
Psychotropic Medications Other Medications
Benzodiazepines Calcium channel blockers
Carbamazepine Proton pump inhibitors
Tricyclic antidepressants Fentanyl
Valproate Statin medications
Nonbenzo hypnotics Loratadine
Mirtazapine Antifungal medications
With the drug interaction between fluoxetine and paroxetine and codeine-based pain medications, patients can experience reduced pain relief because the CYP2D6 inhibition will reduce conversion of codeine and related medications (hydrocodone, oxycodone) to the clinically effective metabolite (morphine, hydromorphone, oxymorphone).
Fluoxetine and fluvoxamine are potent inhibitors of cytochrome CYP2C19 (fluvoxamine more so than fluoxetine). Sertraline is a modest inhibitor of this enzyme. Here is a partial list of affected medications:
Psychotropic Medications Other Medications
Tricyclic antidepressants Proton pump inhibitors (ex. Omeprazole)
Diazepam Proguanil
Propranolol
Fluvoxamine is a fairly strong inhibitor of cytochrome CYP3A4. Here is a partial list of affected medications:
Psychotropic Medications Other Medications
Benzodiazepines Calcium channel blockers
Carbamazepine Proton pump inhibitors
Tricyclic antidepressants Fentanyl
Valproate Statin medications
Nonbenzo hypnotics Loratadine
Mirtazapine Antifungal medications
Trazodone Macrolide antibiotics
Hormone replacement
Fluvoxamine is a potent inhibitor of cytochrome CYP2C9, which can affect the following medications:
Psychotropic Medications Other Medications
No significant interactions Glyburide/Glypizide
ARBs (ex. Losartan)
Warfarin
Phenytoin
Ibuprofen/Naproxen
Fluvoxamine is also a potent inhibitor of cytochrome CYP1A2, which can affect the following medications:
Psychotropic Medications Other Medications
Some antipsychotic medications Warfarin
Tricyclic antidepressants Acetaminophen
Mirtazapine Methadone
It is also important to be aware of the risk of serotonin syndrome (increase heart rate, sweating, myoclonus, hyperthermia, and agitation) when combining certain medications with SSRIs because it can be life threatening. MAOIs are contraindicated with SSRIs for this and other reasons (the combination can also increase the risk of hypertensive crisis). Be cautious when combining SSRIs with Tramodol, Meperidine, St. John’s Wort (an herbal supplement used for mild depression), or dextromethorphan.
Some studies suggest that NSAIDs can reduce the efficacy of SSRI medications, although the overall data is inconclusive. However, the combination is also likely to lead to increased gastrointestinal side effects.
It is our hope that this discussion is helpful for providers in the primary care setting as they are prescribing SSRIs in conjunction with other medications for their patients.
References:
- Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). http://medicine.iupui.edu/clinpharm/ddis/table.aspx. Accessed 12/14/12.
- Albers LJ, MD et al. Handbook of Psychiatric Drugs. 2008 Edition. University of California, Irvine.