SELECTIVE SEROTONIN REUPTAKE INHIBITORS

  • Understand the interaction between SSRIs and MAOIs – cannot be used together due to life threating serotonin syndrome.
Structure/Class
  1. SSRIs – examples are fluoxetine, citalopram and escitalopram
Pharmacodynamics
  1. Mainly bind to SERT.
    • Minimal histaminergic, adrenergic or muscarinic blockade.
Absorption/administration
  1. PO
Distribution
  1. Very lipophilic drug
  2. Strongly protein bound and large Vd: 20-45L/kg à non-dialysable toxin.
Metabolism
  1. Hepatic mainly
    • Note that fluoxetine is metabolized to norfluoxetine, its active metabolite. Norfluoxetine’s T ½ is 3x that of fluoxetine and therefore fluoxetine has the longest half-life of all SSRIs.
    • This is important because fluoxetine must be stopped at least 4 weeks before commencing a MAO-I.
    • Fluoxetine, paroxetine and fluvoxamine are all strong inhibitors of CYP systems.
    • Citalopram, escitalopram and sertraline are more modest.
Excretion
  1. Urinary
Indications
  1. Depressive disorders
  2. Anxiety disorders, including OCD.
Contraindications
  1. Concurrent use of MAO-I is an absolute contraindication
Special precautions
Interactions
  1. MAO-I
  2. TCA and Calcium channel blockers have increased activity due to enzyme inhibition by fluoxetine.
Adverse events
  1. Due to too much serotonin in the CNS
    • Nausea/vomiting/diarrhea
    • Reduced libido
    • Headache and insomnia
    • Weight gain
    • Discontinuation syndrome (dizziness, paraesthesia)
Dosing/administration
Toxicology
  1. Use activated charcoal
  2. BZD may be useful for seizures
Withdrawal syndrome
Special notes