Also known as dual-uptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs) are commonly prescribed by physicians and psychiatrists to treat depression and anxiety. SNRIs, developed in the mid-1990s, are very similar to another category of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), but they have a slightly broader effect on chemical processes in the brain, and some individuals who do not respond to SSRIs may benefit from an SNRI. Studies have shown that SNRIs may be slightly more effective than SSRIs but that they may cause more side effects in some individuals.

Brand Name SNRIs

Effexor is available in both an immediate- and extended-release formula. Certain mental health issues will benefit more from one SNRI than the other. In some cases, it is a matter of trial and error to discover the best SNRI for treatment in a particular situation.

How Do SNRIs Work?

SNRIs act on serotonin transporters (SERTs) and norepinephrine transporters (NETs), which are glycoproteins present in synapses. Their function is to take extra neurotransmitters from these synapses and transfer them back to presynaptic nerves for further use.

By inhibiting the activity of these transporters, SNRIs increase the quantities of both neurotransmitters in the neurons. The increased concentration changes mood and enhances the alertness of a person experiencing symptoms of depression. These chemical messengers are responsible for regulating mental and physical processes other than a person’s emotional state, including sexual and romantic love, trauma, and obsessive compulsions.

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Sometimes SNRIs are prescribed for the treatment of health problems seemingly unrelated to depression or anxiety. Chronic pain conditions, such as fibromyalgia and neuropathic pain associated with diabetic neuropathy and stress urinary incontinence (SUI) in women, have responded well to certain SNRI medications, although researchers are trying to figure out the exact reason for this. Diabetic neuropathy and migraines have also both been shown to improve in some people with the use of Effexor, which is also used to treat chronic fatigue and some symptoms of menopause.

Additionally, it should be noted that antidepressant medications tend to have the best outcome when those people taking them also participate in some type of therapy. Medications can be useful for treating the symptoms of depression and anxiety, but they do not address the underlying root causes, emotions, or circumstances that lead to or contribute to mental health conditions. It is generally recommended that individuals taking antidepressant medications also find a qualified therapist to speak with.

Side Effects

Scientists are only beginning to understand the extent of the functions that serotonin and norepinephrine perform in the human brain. Because neurotransmitters are so involved in all physiological activities, all antidepressants carry some risk of unwanted side effects. As is the case with all antidepressant medications, individuals taking an SNRI may respond in different ways: they may experiencing side effects that vary in severity from severe to minor, or they may experience no side effects at all.

Side effects that an individual taking an SNRI might experience include:

  • Cardiovascular effects: Hypertension along with increased heart rate may occur. Sustained hypertension risk was noticed in 2.3% of people in controlled studies. Use of these agents may increase serum concentration of low-density lipoprotein (LDL), cholesterol, and triglycerides. This may increase the risk of atherosclerosis and strokes. Orthostatic hypotension—the scientific name for the faint feeling you get when standing up or stretching too quickly—and fainting have been reported as well.
  • Gastrointestinal effects: Constipation, dry mouth, anorexia, weight gain, and nausea are some common adverse gastrointestinal effects of SNRIs.
  • Nervous system effects: The most common effects on the nervous system include dizziness, headache (unrelated to blood pressure), drowsiness, sleep disturbances (insomnia, hypersomnia), confusion, and memory loss. At high doses, anxiety, depression, and feelings of suicidal ideation may increase. Additionally, seizures have been reported in some cases.
  • Possible effects on the liver: Liver damage is likely when a person is already experiencing chronic liver disease.
  • Side effects on the urinary and reproductive systems: Impotence, delayed and premature ejaculation, and anorgasmia have been reported. Hyponatremia (dangerously low sodium) is a major adverse effect of SSRIs and SNRIs.
  • Abnormal bleeding: Abnormal bleeding must be reported to your physician. SNRIs should be used with caution if a person is taking anticoagulants such as warfarin or aspirin.
  • Pregnancy and SNRIs: In animals, this class of drugs has shown teratogenic (fetus or embryo development) effects. Their use is contraindicated in pregnancy and for nursing mothers and any risks should be thoroughly weighed with a qualified physician before using SNRIs while pregnant or nursing. According to a 2010 study, the risk of miscarriage in women using antidepressants while pregnant increased by 68%, and the SNRI Effexor was shown to slightly increase the risk of spontaneous abortion. The same study found that combining antidepressants may double miscarriage risk.
  • Other effects: Visual disturbances, mydriasis (pupil dilation), thrombocytopenia (low blood platelet count), anemia, alopecia (hair loss), arthralgia (consistent join pain), and lupus-like syndrome are found in some people.

Drug Interactions

Certain substances and medications should not be used with SNRIs, including:

To avoid adverse drug reactions, be sure to discuss any medications you are currently taking with your psychiatrist or doctor before you begin taking any antidepressant medication.

Withdrawal from SNRIs

A washout period of at least 15 to 20 days is required after the discontinuation of SNRI drugs. Officially, there is no potential for addiction with SNRIs. Nevertheless, suddenly discontinuing an SNRI medication may lead to unpleasant withdrawal symptoms such as nausea, headache, lethargy, and flu-like symptoms. Doctors usually wean people off an SNRI prescription rather than stopping all at once. 


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