SNRIs – Serotonin and Norepinephrine Reuptake Inhibitors

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Antidepressant SNRIs are dual uptake inhibitors that work to relieve depression symptoms, such as irritability and sadness. Here’s how dual reuptake inhibitors work and what side effects they may cause.
By Mayo Clinic staff

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 (reuptake) into cells in the brain. Although the precise mechanism of action isn’t clear, it’s thought that these higher levels enhance neurotransmission — the sending of nerve impulses — and so improve and elevate mood. Medications in this group of antidepressants are sometimes called dual reuptake inhibitors.

Antidepressants, in general, may also work by playing a neuroprotective role in how they relieve anxiety and depression. It’s thought that antidepressants may increase the effects of brain receptors that help nerve cells keep sensitivity to glutamate — an organic compound of a nonessential amino acid — in check. This increased support of nerve cells lowers glutamate sensitivity, providing protection against the glutamate overwhelming and exciting key brain areas related to anxiety and depression.

Therapeutic effects of antidepressants may vary in people, due in part to each person’s genetic makeup. It’s thought that people’s sensitivity to antidepressant effects, especially selective serotonin reuptake inhibitor effects, can vary depending on:

* How each person’s serotonin reuptake receptor function works
* His or her alleles — the parts of chromosomes that determine inherited characteristics, such as height and hair color, which combine to make each person unique

Antidepressant medications are often the first treatment choice for adults with moderate or severe depression, sometimes along with psychotherapy. Although antidepressants may not cure depression, they can help you achieve remission — the disappearance or nearly complete reduction of depression symptoms.

SNRIs approved to treat depression
Here are the SNRIs 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 some 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.

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 a certain SNRI or have different side effects with a different SNRI. 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

Nausea is less common with the extended-release form of SNRIs.

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). Because of this, don’t take any SNRIs while you’re taking any MAOIs or within two weeks of each other. Serotonin syndrome can also occur when SNRIs are taken with other medications, including:

* Pain relief medication such as tramadol (Ultram)
* Migraine medications such as sumatriptan (Imitrex) and rizatriptan
* Supplements that affect serotonin levels, such as St. John’s wort

Serotonin syndrome requires immediate medical treatment. Signs and symptoms include:
* Confusion
* Restlessness
* Hallucinations
* Extreme agitation
* Fluctuations in blood pressure
* Increased heart rate
* Nausea and vomiting
* Fever
* Seizures
* Coma

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.

Use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) or anticoagulants, such as warfarin (Coumadin), while taking SNRIs may increase the risk of gastrointestinal bleeding and should be monitored by your doctor.

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.

Suicidal feelings and SNRIs
In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior in those ages 18 to 24, particularly during the first one to two months of 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 when starting treatment or changing dosage, or you may need to stop the medication if your symptoms worsen. Adults age 65 and older taking antidepressants have a decreased risk of suicidal thoughts.

Talk with your doctor or mental health provider to nix your irritability, sadness or anger and improve your mood with dual reuptake inhibitor SNRIs. Feel good again.