Medicine & USMLE


Psych Pharm
  1. Lithium
  2. Typical Antipsychotics
  3. Atypical Antipsychotics
  4. SSRIs
  5. SNRIs
  6. Tricyclic Antidepressants (TCAs)
  7. Monoamine Oxidase Inhibitors (MAOIs)
  8. Bupropion
  9. Mirtazapine
  10. Trazadone
  11. Vilazodone
  12. Vortioxetine
  13. Buspirone
  14. Varenicline


Serotonin and norepinephrine reuptake inhibitors or SNRIs for short, are a class of medications that include venlafaxine and duloxetine. SNRIs work to increase serotonin and norepinephrine signaling in the brain, by blocking the reuptake of or transport of serotonin and norepinephrine out of the synapse. Clinically, SNRIs are used to treat  depression, anxiety disorders, or neuropathic pain. Some of the key adverse effects of SNRIs include sexual dysfunction, serotonin syndrome, and increased blood pressure.

Key Points

  • Serotonin and norepinephrine reuptake inhibitors (SNRIs)
    • Drug names:
      • Venlafaxine, Desvenlafaxine
      • Duloxetine
      • Milnacipran, Levomilnacipran
    • Mechanism:
      • Block serotonin (5-HT) and norepinephrine reuptake
        • Reduced reuptake by presynaptic neuron increases serotonin and norepinephrine in synaptic clefts
          • Capable of activating serotonin receptors on the postsynaptic neuron
          • May play a role in the mood-altering effects of these drugs.
    • Indications:
      • Depression (major depression disorder)
      • Anxiety disorders
        • Includes Generalized anxiety disorder, PTSD, OCD, Panic disorder, Social anxiety disorder
      • Neuropathic pain
        • Especially for diabetic peripheral neuropathy and fibromyalgia
        • Also used for Migraine prophylaxis
    • Adverse effects
      • Script only--mention most common are nausea, dizziness, potentially sexual dysfunction
      • Sexual impotence
        • SNRIs can cause anorgasmia and decreased libido (similar to SSRIs)
      • Serotonin syndrome
        • Occurs when taking SNRIs with another drug that increases levels of 5-HT
          • Contraindicated with MAOI, need to wait 2 weeks between stopping SNRI and starting MAOI and vice versa
          • Examples: TCAs, MAOIs, linezolid, St. John’s wort
        • Characterized by a clinical triad:
          • Hyperactivity (clonus, hyperreflexia, hypertonia, seizures)
          • Autonomic instability (high temperature, sweating, tachycardia, diarrhea)
          • Altered mental status
            • Tip: Differentiate from neuroleptic malignant syndrome due to the presence of absence of hyperreflexia and clonus. If clonus, think serotonin syndrome. If a patient has rigid muscles with no clonus, think NMS!
        • Treat with: Cyproheptadine
          • A 5-HT2 receptor antagonist
      • Increased blood pressure (hypertension)
        • Dose-dependent effect due to ↑ NE, most notably in venlafaxine
      • Antidepressant discontinuation syndrome
        • Generally described a s flu-like symptoms (nausea,fatigue, headaches)
        • Discontinuing an SSRI/SNRI requires a taper. A sudden discontinuation of an SSRI/SNRI or rapid dose reduction can produce a variety of symptoms (GI distress, fatigue, flu-like feelings, depressed and irritable mood, fatigue, feeling of electric shocks). Basically, if someone feels bad after stopping an SSRI/SNRI, think about this!
          • Treat by:
            • Restarting the antidepressant or raising the dose