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SNRIs (Serotonin Norepinephrine Reuptake Inhibitors)

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 are very similar to another category of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), but with a slightly broader effect on chemical processes in the brain. 

Brand Name SNRIs

Effexor is available in both an immediate- and extended-release formula. Certain mental health issues will benefit more from one or 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. Unlike many tricyclic antidepressants, SNRIs have less affinity for α-adrenergic, histamine, and cholinergic receptors, and thus produce fewer adverse effects than most other classes of antidepressants.

Additionally, it should be noted that antidepressant medications tend to have the best outcome for people taking them when combined with 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. Finding a qualified therapist to speak with is recommended for you to get the most out of your treatment with antidepressant medications.

Side Effects

Scientists are only beginning to understand all 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, everyone responds differently and may experience a different set of side effects. Most people, however, experience minor and insignificant side effects and have no problem following their doctors' prescriptions.


Taking SNRIs may lead to unwanted side effects, such as:

  • 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: 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, in some cases seizures have been reported.
  • 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: There is not enough data concerning taking SNRIs during pregnancy to make a concrete recommendation. In animals, however, 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 and rewards should be thoroughly weighed with a qualified physician before using SNRIs while pregnant or nursing.
  • 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 of 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. 



  1. Mayo Clinic. (n.d.). Depression (Major Depression). Retrieved from http://www.mayoclinic.com/health/antidepressants/MH00071 
  2. National Institute of Mental Health. Mental Health Medications. Retrieved from http://www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.shtml#pub8
  3. Gether, U. et al. (2006). Neurotransmitter Transporters: Molecular Function of Important Drug Targets. Trends Pharmacol Sci, 27(7), 375.
  4. Stein, D.J., Kupfer, D.J., and Schatzberg, A.F. (2006). American Psychiatric Publishing Textbook of Mood Disorders. American Psychiatric Publishing, Inc.
  5. Stein, M.B. and Stein, D.J. (2008). Social Anxiety Disorder. Lancet, 371(9618), 1115.
  6. Schatzberg, A.F., Cole, J.O., and DeBattista, C. (2007). Manual of Clinical Psychopharmacology, 6th ed. American Psychiatric Publishing, Inc.


Last Update: 02-09-2015


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