Serotonin-norepinephrine reuptake inhibitors (SNRIs) were first introduced in the mid-1990s. This class of antidepressants works by inhibiting the reabsorption of not one but two important brain chemicals: serotonin and norepinephrine. That’s why these drugs are sometimes called dual reuptake inhibitors or dual-acting antidepressants.

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How SNRIs Work

Depression is associated with low levels of certain brain chemicals. These chemicals, which are collectively called neurotransmitters, carry messages between brain cells. Certain neurotransmitters—including serotonin and norepinephrine—are known to affect mood. Serotonin is sometimes called a “feel good” chemical because it is associated with positive feelings of wellbeing. Norepinephrine is related to alertness and energy. SNRIs increase the amount of available serotonin and norepinephrine in the brain by blocking the reabsorption of those neurotransmitters.

Who Should Take SNRIs?

Because SNRIs affect two neurotransmitters, they may be an effective form of treatment for patients who have failed to respond to single-acting antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). Some research suggests that patients with severe depression may respond better to an SNRI.

SNRIs may also be a good choice for patients who struggle with anxiety. At least one SNRI, desvenlafaxine, may be an option for patients who are taking medications for other health conditions. Compared to other antidepressants, desvenlafaxine has a lower risk of drug-to-drug interactions.

Women who are nursing or pregnant should avoid taking SNRIs. Babies delivered to mothers who take SNRIs during the second half of pregnancy may experience withdrawal symptoms, including difficulty breathing, feeding problems, and tremors. SNRIs also pass into breast milk. Certain SSRIs may be better options for pregnant or nursing mothers.

People with liver problems or high blood pressure may also want to avoid SNRIs. If treatment with a SNRI is necessary, your doctor will monitor your liver function periodically via blood tests to watch for any further damage.

Individuals who take aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, and blood-thinning medications such as warfarin (Coumadin) should use SNRIs with caution. Taking an SNRI with those drugs may further inhibit blood from clotting, thus increasing the risk of severe bleeding from a cut or scrape.

Possible Side Effects

Although all SNRIs work similarly, minor differences may affect the side effect profile. If you experience unpleasant side effects while taking an SNRI, talk to your doctor. Switching to another antidepressant—even another SNRI—might alleviate the problem.

Possible side effects 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
  • sexual dysfunction (inability to maintain an erection or orgasm)
  • constipation
  • fluid retention (especially in older adults)

Types of SNRIs

There are currently three SNRIs on the market. The generic names are listed below with their brand-name counterparts in parentheses.

  • desvenlafaxine (Pristiq)
  • duloxetine (Cymbalta)
  • venlafaxine (Effexor, Effexor XR)

What the Expert Says

“There is evidence that some of the SNRIs might be a tad more effective, in general, than SSRIs,” says Dr. Danny Carlat, M.D., associate clinical professor of psychiatry at Tufts University School of Medicine. “But they also tend to cause more side effects. SNRIs can cause things like night-time sweating or even sweating during the day.”

Carlat adds that some people who are coming off of an SNRI tend to experience withdrawal symptoms—such as dizziness, lack of coordination, insomnia, and tearfulness. Patients have to be careful to gradually reduce their use of the medication.