SNRIs and SSNRIs (and NRIs) for Bipolar Disorder

What's the Difference Between SSNRIs and SNRIs and NRIs?

Effexor pills, which are used to treat depression and other ailments.
Joe Raedle/Getty Images

There is some confusion about the terms SSNRI and SNRI. What is the difference between selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) and selective norepinephrine inhibitors (SNRIs), and can these terms be used interchangeably?

SSNRIs vs SNRIs - The Confusion in Terms

SNRI stands for both selective serotonin-norepinephrine reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor.

SSNRI stands only for selective serotonin-norepinephrine reuptake inhibitor but is used interchangeably with SNRI now and rarely used alone. Then there are also selective norepinephrine reuptake inhibitors, commonly referred to as NRIs.

There Are Also SSRIs

Yet another category of medications, SSRIs or selective serotonin reuptake inhibitors, can make this even more confusing. SSRIs include medications such as Prozac, Paxil, Zoloft, and Celexa. As with SSNRIs or SNRIs, they can precipitate mania in people with bipolar disorder and are rarely used alone.

Function of SSNRIs and SNRIs

SSNRIs or SNRIs work by inhibiting the reuptake of neurotransmitters, the chemicals which transmit messages through the brain. Reuptake inhibitors work by inhibiting the reuptake of these chemicals by cells from which they were secreted, effectively increase the amount of the chemical present in the synapse (and able to bind with the next nerve cell to send a message.) In other words, a reuptake inhibitor would work in a way similar to canceling a garbage service that is sent to pick up waste.

In this case, however, the "waste" is a chemical which performs an important role in determining and regulating mood.

SSNRIs (or SNRIs) inhibit both the neurotransmitters serotonin (sometimes referred to as the "feel good" chemical) and norepinephrine, resulting in an improvement in mood.

Drugs in this category include:

Side Effects of SNRIs

Common side effects vary between different people but may include:

  • Dizziness
  • Sweating
  • Dry mouth
  • Upset stomach
  • Fatigue
  • Headache
  • Constipation
  • Sexual issues
  • Anxiety
  • Difficulty sleeping
  • Appetite loss

Selective Norepinephrine Reuptake Inhibitors (NRIs)

NRIs are medications which inhibit the reuptake of norepinephrine but do not increase the reuptake of serotonin in the brain. They are used for ailments like attention deficit/hyperactivity disorder (ADHD), depression and anxiety. Common medications include:

  • Strattera (atomoxetine) is mainly used to treat ADHD.
  • Ludiomil (maprotiline) is used for depression and anxiety.

Side Effects of NRIs

Typical side effects of NRIs include:

  • Skin redness
  • Hives
  • Itching
  • Rash
  • Heartbeat irregularity
  • Sexual issues
  • Fatigue or weakness
  • Blurred vision
  • Constipation
  • Light-sensitive skin
  • Upset stomach

SNRIs in Bipolar Disorder

SNRI's may be used for people with bipolar disorder, but it's felt that their use should be limited to the short-term use for acute bipolar depression. Some studies have found antidepressants such as SNRIs helpful in this setting, yet overall, using antidepressants for bipolar depression does not seem to have a significant impact on the natural history of the disease. This is true even when they are used with mood stabilizers or atypical antipsychotic medications. In contrast, longer-term use of SNRIs (or SSRIs) substantially increases the risk of antidepressant-induced mania or hypomania.

Antidepressant-Induced Mania With Bipolar Disorder

As noted, antidepressants such as SNRIs can trigger a manic episode in people with bipolar disorder. If you have bipolar I disorder, you will likely need a mood stabilizer or antipsychotic as well if your doctor recommends an antidepressant medication.

Other Medications Used for Bipolar Disorder

There are several other categories of medications which are commonly used to treat bipolar disorder. These include:

Mood Stabilizers

Like the name describes, mood stabilizers help keep your mood stable and help prevent you from having manic or hypomanic episodes. A few of the medications used as mood stabilizers are actually anticonvulsants used for people with epilepsy too. Some common mood stabilizers are:

  • Lithium
  • Depakote (divalproex sodium)
  • Tegretol (carbamazepine)
  • Lamictal (lamotrigine)

Possible side effects of mood stabilizers are feeling thirsty, rash, upset stomach, seizures, slurring of speech, swelling, tremor, vision changes, irregular heartbeat, having to urinate often, hallucinations and blackouts.


An antipsychotic medication (either a typical antipsychotic or an atypical antipsychotic) may be added or replaced in your treatment regimen if you are still having problems with your mood being either too low or too high. Examples of antipsychotics include:

  • Risperdal (risperidone)
  • Geodon (ziprasidone)
  • Zyprexa (olanzapine )
  • Abilify (aripiprazole)
  • Latuda (lurasidone )

Side effects of antipsychotics may include low blood pressure, blurry vision, dizziness, gaining weight, seizures, drowsiness, dry mouth, vomiting, tics or tremors. low white blood cell count and upset stomach.

Anti-Anxiety Medication

If you are having trouble with anxiety and/or your sleep, your mental health professional may prescribe you an anti-anxiety medication called a benzodiazepine to help. Common ones include:

  • Xanax (alprazolam)
  • Klonopin (clonazepam)
  • Valium (diazepam)
  • Ativan (lorazepam)

Side effects of anti-anxiety medications can include confusion, drowsiness, weakness, breathing difficulties, slurred speech and coordination problems. They are often taken before bed to help you sleep, however, so you may not notice these effects.

A Word From Verywell

While SNRIs can be helpful for people with depression, their role in treating the depression which accompanies bipolar disorder is much less clear. With bipolar disorder, these medications should be used only in combination with a mood stabilizer or antipsychotic medication, and then only short-term for acute bipolar depression when it's thought that the benefits will outweigh the risks.

Studies suggest that long-term use, in addition to the potential of precipitating mania or hypomania, may result in poorer outcomes for people with bipolar disorder. Of course, every person with bipolar disorder is different, and your psychiatrist may feel that longer-term use of these medications will benefit you individually.


Frye, M., McElroy, S., Prieto, M. et al. Clinical Risk Factor an Serotonin Transporter Gene Variants Associated with Antidepressant-Induced Mania. Journal of Clinical Psychiatry. 2015. 76(2):174-80.

McGirr, A., Vohringer, P., Ghaemi, S., Lam, R., and L. Yatham. Safety and Efficacy of Adjunctive Second-Generation Antidepressant Therapy with a Mood Stabiliser or an Atypical Antipsychotic in Acute Bipolar Depression: A Systematic Review and Meta-Analysis of Randomised Placebo-Controlled Trials. Lancet Psychiatry. 2016. 3(12):1138-1146.

Vardi, K., Warner, J., and N. Philip. Effects of Antidepressant Use and Anxiety on Psychiatric Rehospitalization in Bipolar Depression. Annals of Clinical Psychiatry. 2014. 26(3):207-16.

Vieta, E., and M. Garriga. Adjunctive Antidepressants in Bipolar Depression. Lancet Psychiatry. 2016. 3(12):1095-1096.