Serotonin-norepinephrine reuptake inhibitors (SNRIs) were first introduced in the mid-1990s as a class of antidepressant drugs. Because they affect two important brain chemicals — serotonin and norepinephrine — these drugs are sometimes called dual reuptake inhibitors or dual-acting antidepressants.

SNRIs are typically used to treat depression. They may be an effective form of treatment for people who have had unsuccessful treatment with selective serotonin reuptake inhibitors, which only work on one chemical messenger.

SNRIs may also be a good choice for people with anxiety.

Depression is associated with low levels of serotonin and norepinephrine. These are neurotransmitters (chemical messengers) known to affect mood. Serotonin is sometimes called a “feel-good” chemical because it’s associated with positive feelings of wellbeing. Norepinephrine is related to alertness and energy.

It is thought that SNRIs help treat depression by keeping up the levels of these two chemical messengers in your brain. They do this by stopping serotonin and norepinephrine from going back into the cells that released them.

Five SNRIs are currently on the market:

  • desvenlafaxine (Pristiq)
  • duloxetine (Cymbalta)
  • venlafaxine (Effexor, Effexor XR)
  • levomilnacipran (Fetzima)
  • milnacipran (Savella)

Levomilnacipran and milnacipran are only available as brand-name drugs. The others are available as both brand-name and generic drugs. Milnacipran is not approved by the U.S. Food and Drug Administration to treat depression, but your doctor may prescribe it off-label for that purpose.

Read more: What's off-label drug use? »

During pregnancy or breastfeeding

Women who are pregnant or breastfeeding should avoid taking SNRIs unless the benefits of taking them clearly outweigh the risks to the mother and baby. Babies delivered to mothers who take SNRIs during the second half of pregnancy may experience withdrawal symptoms. These include:

  • difficulty breathing
  • feeding problems
  • tremors

SNRIs also pass into breast milk. While all antidepressants may pose a risk to a developing fetus, certain options may be safer for a mother and baby. Talk to your doctor about the best option for you.

People with liver damage or high blood pressure

People with liver problems or high blood pressure may also want to avoid SNRIs. These drugs can increase blood pressure levels. They are also processed in your liver. If you have liver problems, more of the drug may stay in your system longer and lead to an increased risk of side effects. If treatment with a SNRI is necessary, your doctor will monitor your blood pressure or liver function.

Possible side effects of SNRIs include:

  • nausea
  • changes in appetite
  • muscle weakness
  • tremor
  • agitation
  • heart palpitation
  • increased blood pressure
  • increased heart rate
  • headache
  • difficulty urinating
  • dizziness
  • insomnia
  • sleepiness
  • dry mouth
  • excessive sweating
  • constipation
  • fluid retention (especially in older adults)
  • inability to maintain an erection or have an orgasm (in men)

While all SNRIs work similarly, minor differences may affect the side effects for each SNRI.

SNRIs offer another option for tough-to-treat depression or depression with anxiety. Talk to your doctor about these drugs. If you’re currently being treated for depression but not having much luck with your medication, ask if SNRIs may be an option for you.