Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a family of antidepressant medications that affect the brain’s neurotransmitters serotonin and norepinephrine. For those with depression and anxiety, these medications can help with these conditions. However, there are different kinds of medication within the SNRI category that have different effects on the body. If you’re trying to compare SSRI and SNRI options to determine the right treatment path, understanding these differences is an important first step.
What Is an SNRI?
SNRIs, as the name suggests, inhibit the reuptake of serotonin and norepinephrine in the brain. Serotonin and norepinephrine are involved in regulating mood, sleep, energy, and attention. Both of these neurotransmitters, or chemical messengers, are released from nerves in the brain. The chemical then either attaches to other nerve receptors in the brain or reuptakes or reabsorbs, into the nerve that made it to be recycled and released again. The use of an SNRI blocks this reabsorption process, which increases the amount of serotonin and norepinephrine available for the brain to absorb, thereby relieving the symptoms of Depression and anxiety. For patients exploring the best SNRI Depression treatment for their needs, it helps to understand how this mechanism differs from other antidepressant classes.
SNRI vs SSRI
SNRIs are commonly mistaken for selective serotonin reuptake inhibitors (SSRIs), as both are commonly used to treat depression. When evaluating SSRI vs SNRI medications, the most important distinction lies in which neurotransmitters each class targets. While both drug types prevent the reabsorption of neurotransmitters, SNRIs regulate serotonin and norepinephrine, whereas SSRIs exclusively control serotonin levels. SSRIs are more commonly prescribed, as they have been around longer and usually have less risk of causing side effects. However, SNRIs can sometimes be more effective than SSRIs.
Key Differences When You Compare SSRI and SNRI Medications
When patients and providers compare SSRI and SNRI medications side by side, several factors come into play; SSRIs tend to have fewer side effects and are often a first-line treatment, while SNRIs may offer broader symptom relief due to their dual mechanism. For patients with both Depression and chronic pain, SNRIs vs SSRIs may favor the SNRI class, as norepinephrine also plays a role in pain modulation. Understanding the differences between SNRIs vs SSRIs can help patients make more informed decisions with their doctors; those reviewing a full SSRI vs SNRI drug list will notice that the SNRI class, while smaller, covers a wider range of approved conditions.
SSRI vs SNRI Drug List: The 5 Major SNRIs and Finding the Right Fit
All SNRI’s regulate serotonin and norepinephrine, but they have subtle differences in how much absorption they block, as well as differences in side effects. Many with Depression and anxiety have trouble finding the correct medication to treat their symptoms, and it can take months or even years to find one that works effectively. One recently published study comparing different SNRI’s found a surprising number of differences between the five major SNRIs.
Below is a breakdown of the medications on the SNRI side of the SSRI vs SNRI drug list. Each of these five SNRIs has distinct characteristics that affect how it is prescribed and how patients respond to treatment.
Venlafaxine
Venlafaxine (Effexor ™) was approved by the FDA in 1993 and was the first SNRI approved in the United States. Its half-life (the time it takes for the blood plasma concentration of a drug to reduce to half its original value) for the immediate release is five hours (requiring twice a day dosing), whereas the extended-release has a half-life of 11 hours, which allows for once a day dosing. As for reuptake, it was found to block about 30 times more serotonin than norepinephrine. It inhibits each in a sequential manner with serotonin reuptake being initially inhibited followed by norepinephrine reuptake inhibition, which leads to the initial side effects related more to serotonin (headaches, nausea, and sexual dysfunction) and subsequent side effects involving both (activation, dry mouth, and night sweats). Venlafaxine is frequently cited as a contender for the best SNRI for Depression due to its long track record and broad evidence base.
Duloxetine
Duloxetine (Cymbalta ™) has the most FDA-approved uses among the best SNRI Depression options and, unlike Venlafaxine, is proven to relieve non-psychiatric conditions, like neuropathy, fibromyalgia, and osteoarthritis. Its half-life (12 hours) allows for once-a-day dosing. Like Venlafaxine, it is susceptible to genetic polymorphism and inhibits serotonin and norepinephrine in turn. Many clinicians consider Duloxetine among the best SNRI for Depression, particularly for patients who also experience chronic pain conditions.
Desvenlafaxine
Desvenlafaxine (Pristiq ™) received approval from the FDA in 2008. The drug resembles Venlafaxine structurally, being Venlafaxine’s only active metabolite. It has an 11-hour half-life (allowing for once-a-day dosing) and is 10 times more potent in blocking serotonin reabsorbing than norepinephrine. It’s unknown what order this medication blocks neurotransmitters, but it has been observed weakly blocking dopamine reuptake, just like Venlafaxine and Duloxetine. Desvenlafaxine is a notable entry on any SSRI vs SNRI drug list due to its simplified metabolism and predictable dosing.
Milnacipran
Milnacipran (Savella TM) is not approved to treat Depression but rather only fibromyalgia. The chemical makeup of the drug is two-fold: D-milnacipran with a half-life of 8-10 hours and l-milnacipran with a half-life of 4-6 hours. It avoids interaction with the isoenzymes that cause drug interactions and genetic polymorphism. It had the most equal reuptake rate of all drugs studied, and may show signs of creating higher amounts of norepinephrine. It is the only drug with equal effects on both neurotransmitters without also affecting dopamine. While it does not appear on a typical best SNRI Depression ranking, its unique pharmacology makes it relevant in the broader SNRIs vs SSRIs discussion.
Levomilnacipran
Levomilnacipran (Fetzima ™) is the most recent medication approved for treating major Depression. It was developed exclusively for a one-a-day extended-release form, which makes it easier for patients to stick to its regimen, unlike twice-daily medications like Milnacipran. Its half-life of twelve hours proves its ability to retain control of the body, as does the fact that the chemical makeup of the drug is vastly unchanged after it exits the body. Like milnacipran, the drug has no effect on dopamine and affects reuptake inhibition of serotonin and norepinephrine equally at any dose.
How to Choose the Best SNRI for Depression
Selecting the best SNRI Depression treatment depends on a variety of factors like dosage, ability to interact with other drugs, and time spent in the body. Whether the variable influences on norepinephrine and serotonin reuptake among the SNRIs causes any meaningful clinical differences is unclear.
Selecting the best SNRI for Depression depends on a range of individual factors, including co-occurring conditions, side effect tolerance, and how a patient has responded to previous medications. For example, patients with fibromyalgia or chronic pain may benefit most from Duloxetine, while those seeking a well-studied first-line SNRI may start with Venlafaxine. When weighing SSRI vs SNRI options, it is important to work closely with a psychiatrist who can review your full medical history and tailor the approach. In many cases, patients cycle through several entries on the SSRI vs SNRI drug list before finding the medication that works effectively for them.
Need More than SNRIs? Mid City TMS Can Help
While some people will find the right medication to effectively treat their Depression, others will discover medication is not enough to relieve them of their symptoms. Whether you’ve tried medications from the SNRIs vs SSRIs categories or other antidepressant classes, alternate treatments like transcranial magnetic stimulation (TMS) can help.
TMS is a procedure that uses electromagnetic pulses to treat Depression by activating the parts of the brain with suboptimal functioning. TMS is approved by the FDA to be a safe, effective treatment for Depression and can be used alone or in conjunction with antidepressants, including SNRIs. If medications on the SSRI vs SNRI drug list have not provided adequate relief, TMS may be a strong next step. To learn more about how to compare SSRI and SNRI treatments alongside alternatives like TMS, contact us today!
Sources:
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Mayo Clinic. (n.d.). Antidepressants: Selecting one that’s right for you. Mayo Clinic. Retrieved from https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20044970
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Monteggia, L. M., Malenka, R. C., & Deisseroth, K. (2014). Divergent mechanisms of antidepressant efficacy. Biological Psychiatry, 73(12), 1107-1114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008300/