What medications interact with Zoloft (sertraline)?

Medication Interactions with Sertraline (Zoloft)

Sertraline has significant interactions with multiple medications, most importantly with MAOIs which can cause potentially life-threatening serotonin syndrome, and should never be combined. 1

Major Interactions to Avoid

Absolutely Contraindicated

• Monoamine Oxidase Inhibitors (MAOIs) 2, 1

  • Examples: phenelzine, isocarboxazid, moclobemide, isoniazid, linezolid
  • Risk: Life-threatening serotonin syndrome
  • Requires 14-day washout period between stopping MAOIs and starting sertraline (and vice versa)

• Pimozide (Orap) 1

  • Risk: QT prolongation, potentially fatal arrhythmias
  • Even low doses (2mg) of pimozide showed 40% increase in pimozide levels with sertraline

High-Risk Interactions

1. Other Serotonergic Drugs 2, 1

   • SSRIs, SNRIs, tricyclic antidepressants
   • Triptans (migraine medications)
   • Tramadol, meperidine, methadone, fentanyl (opioids)
   • St. John's Wort, L-tryptophan
   • Risk: Serotonin syndrome with symptoms ranging from mild (confusion, agitation) to severe (hyperthermia, seizures, death)

2. Drugs Metabolized by CYP2D6 1

   • Antiarrhythmics (propafenone, flecainide)
   • Antipsychotics
   • Tricyclic antidepressants
   • Risk: Increased blood levels of these medications, potential toxicity

3. Anticoagulants/Antiplatelets 2, 1

   • Warfarin, NSAIDs, aspirin
   • Risk: Increased bleeding risk (8% increase in prothrombin time)
   • Requires close monitoring of INR/prothrombin time

Moderate Interactions

1. Drugs Highly Bound to Plasma Proteins 1

   • Warfarin, digitoxin
   • Risk: Displacement from protein binding sites, altered drug levels

2. CNS Depressants

   • Benzodiazepines, alcohol, sedatives
   • Risk: Enhanced sedation, impaired psychomotor function

3. Drugs Affecting QT Interval 2

   • Class Ia and III antiarrhythmics
   • Some antipsychotics
   • Risk: QT prolongation, arrhythmias

4. Cimetidine 1

   • Increases sertraline levels by 50%
   • Risk: Enhanced side effects of sertraline

Monitoring Recommendations

For High-Risk Combinations

• Monitor for signs of serotonin syndrome within 24-48 hours of combining medications 2
  • Mental status changes: confusion, agitation, anxiety
  • Neuromuscular symptoms: tremors, clonus, hyperreflexia, muscle rigidity
  • Autonomic symptoms: hypertension, tachycardia, hyperthermia, diaphoresis

For Anticoagulants

• Check prothrombin time/INR within 1-2 weeks of starting sertraline 1
• Monitor for signs of bleeding: ecchymosis, epistaxis, petechiae

Special Populations

• Patients with seizure disorders: Use caution as SSRIs may lower seizure threshold 2
• Patients with bipolar disorder: Risk of triggering mania/hypomania 2
• Patients with liver impairment: Higher risk of drug interactions due to altered metabolism 1

Clinical Pearls

• Sertraline has fewer drug interactions compared to fluoxetine due to its shorter half-life
• When switching between sertraline and MAOIs, a 14-day washout period is mandatory 1
• Avoid abrupt discontinuation of sertraline to prevent discontinuation syndrome 2
• For patients requiring pain management, morphine, codeine, and oxycodone are safer options than tramadol or meperidine when combined with sertraline 3

By understanding these interactions and implementing appropriate monitoring, clinicians can minimize adverse events while effectively treating patients with sertraline.