Selective Serotonin Reuptake Inhibitor - Contraindications and Drug Interaction

Contraindications and Drug Interaction

One major contraindication of SSRIs is the concomitant use of MAOIs (monoamine oxidase inhibitors). This is likely to cause severe serotonin syndrome/toxidrome.

People taking SSRIs should also avoid taking pimozide (an antipsychotic diphenylbutylpiperidine derivative). Tramadol hydrochloride (or Ultram, Ultracet) can, in rare cases, produce seizures when taken in conjunction with an SSRI or tricyclic antidepressant. Liver impairment is another contraindication for medications of this type.

SSRIs may increase blood levels and risk of toxicities of certain medications:

  1. highly protein-bound medications like warfarin (coumadin) and digoxin
  2. antiarrhythmic agents like propafenone (Rythmol) or flecainide (Tambocor)
  3. beta blockers like metoprolol (Toprol xl) or propranolol (Inderal)
  4. Tricyclic antidepressants like amitriptyline (Elavil, Endep) etc.
  5. triptans like sumatriptan (Imitrex, Imigran) etc.
  6. benzodiazepines like alprazolam (Xanax) or diazepam (Valium)
  7. carbamazepine (Tegretol)
  8. cisapride (Propulsid)
  9. clozapine (Clozaril)
  10. ciclosporin (Neoral)
  11. haloperidol (Haldol)
  12. phenytoin (Dilantin)
  13. pimozide (Orap)
  14. theophylline (Theo-dur)

Certain drugs may increase toxicities of SSRIs:

  1. alcohol and other CNS depressants
  2. methylene blue dye
  3. diuretics (water pills)
  4. MAOIs – possibly fatal serotonin syndrome/toxidrome
  5. sympathomimetic drugs like pseudoephedrine (Sudafed)
  6. lithium
  7. sibutramine (Meridia)
  8. MDMA (ecstasy)
  9. zolpidem (ambien)
  10. dextromethorphan (cough suppressant) – increased risk of serotonin syndrome/toxidrome
  11. tramadol (synergistic serotoninergic effect said to increase risk of seizure or serotonin syndrome/toxidrome)
  12. pethidine/meperidine – increased risk of serotonin syndrome/toxidrome
  13. herbal Saint John's wort or yohimbe – increased risk of serotonin syndrome/toxidrome

Painkillers of the NSAIDs drug family may interfere and reduce efficiency of SSRIs:

  1. Aspirin
  2. Ibuprofen (Advil,Nurofen)
  3. Naproxen (Aleve)

SSRIs also directly interfere with ligands of 5-HT receptors, like the psychedelics and entactogens. SSRIs strongly diminish the effects of tryptamines (e.g. psilocybin and LSD), and phenethylamines (e.g. the 2C family), and almost completely eliminate the serotonergic effects of MDxx (e.g. MDMA). The exact mechanism that causes this interaction is still unclear.

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