Serotonin and norepinephrine reuptake inhibitors (SNRIs)

SNRIs are a type of antidepressant that can relieve the symptoms of depression, such as sadness and irritability. Learn how they work and what side effects they can cause.

Certain brain chemicals called neurotransmitters are associated with depression, including the neurotransmitters serotonin (ser-oh-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin). Research suggests that abnormalities in neurotransmitter activity can affect mood and behavior.

How SNRIs work

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a type of antidepressant medication that increases the levels of both serotonin and norepinephrine by inhibiting their reabsorption into cells in the brain. Although the precise mechanism of action isn't clear, it's thought that these increased levels enhance neurotransmission — the sending of nerve impulses — and thereby improve and elevate mood. Medications in this group of antidepressants are sometimes known as dual reuptake inhibitors.

SNRIs approved to treat depression

Here are the SNRIs that have been approved by the Food and Drug Administration specifically to treat depression, with their generic or chemical names followed by available brand names in parentheses:

Duloxetine (Cymbalta)
Venlafaxine (Effexor, Effexor XR)

As with certain other antidepressants, venlafaxine is available in an immediate-release form that requires two or three doses a day and in an extended-release (XR) form that allows you to take it just once a day. Extended-release forms can help reduce nausea.

Some of these medications may also be used to treat conditions other than depression.

Side effects of SNRIs

All SNRIs have the same general mechanism of action and side effects. However, individual SNRIs have some different pharmacological characteristics. That means you may respond differently to certain SNRIs or experience different side effects with different SNRIs. For instance, you may have unpleasant side effects with one SNRI but not another.

Side effects of SNRIs include:

Nausea
Vomiting
Dizziness
Insomnia
Sleepiness
Trouble sleeping
Abnormal dreams
Constipation
Sweating
Dry mouth
Yawning
Tremor
Gas
Anxiety
Agitation
Abnormal vision, such as blurred vision or double vision
Headache
Sexual dysfunction

Serotonin syndrome and SNRIs

A rare but potentially life-threatening side effect of SNRIs is serotonin syndrome. This condition, characterized by dangerously high levels of serotonin in the brain, can occur when an SNRI interacts with antidepressants called monoamine oxidase inhibitors (MAOIs). Serotonin syndrome can also occur when SNRIs are taken with other medications or supplements that affect serotonin levels, such as St. John's wort. Serotonin syndrome requires immediate medical treatment.

Signs and symptoms of serotonin syndrome include:

Confusion
Restlessness
Hallucinations
Extreme agitation
Fluctuations in blood pressure
Increased heart rate
Nausea and vomiting
Fever
Seizures
Coma

Stopping treatment with SNRIs

SNRIs aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including:

Nausea
Headache
Dizziness
Lethargy
Flu-like symptoms

This is sometimes called discontinuation syndrome. Talk to your doctor before stopping so that you can gradually taper off.

Safety concerns with SNRIs

At high doses, venlafaxine can raise blood pressure significantly. Your doctor might monitor your blood pressure regularly, especially if you already have blood pressure problems. Venlafaxine can also raise cholesterol, so you may need periodic blood tests to check your blood cholesterol. Both duloxetine and venlafaxine should be avoided or used with caution if you have narrow-angle glaucoma or raised intraocular pressure.

Suicidal feelings and SNRIs

In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior, particularly early in treatment or when you change your dosage. Be sure to talk to your doctor about any changes in your symptoms. You may need more careful monitoring at the beginning of treatment or upon a change in treatment, or you may need to stop the medication if your symptoms worsen.