Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are one of the newest classes of drugs used in the treatment of depression.  Drugs in this class include:  fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). These drugs are typically as effective as older antidepressants, but they are associated with much less side effects. The use of SSRIs are now also being used for the treatment of eating disorders, panic disorders, OCD, and borderline personality disorder.

Mechanism of action:

  • Act specifically to block the presynaptic reuptake of serotonin in the brain without affecting norepinephrine or dopamine.
  • Basically have no agonist or antagonist activities on any neurotransmitter receptor.
    • Their lack of anticholinergic, antihistaminergic, and adrenergic activities explains their favorable side effect profile.

Major side effects include:  nausea, anorexia, and diarrhea

Metabolism:  All SSRIs are metabolized by the liver

Drug-drug interactions of note:

  • The SSRIs in combination with an MAOI can produce a dangerous serotonin syndrome characterized by tremor, myoclonus, confusion, diaphoresis, diarrhea, and death.
  • Raise blood levels of the tricyclic antidepressants, trazodone, carbamazepine (Tegretol), and benzodiazepines.
  • Administration of L-tryptophan with SSRIs can produce a “milder” form of serotonin syndrome including the presence of myoclonic jerks as a frequent symptom.

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