The Difference Between SSRIs and SNRIs
What SSRIs and SNRIs are, how they differ, what they are used for, and why the choice between them is made with a doctor.
Clinically reviewed by Dr. Ponlawat Pitsuwan, Physician and Addiction Medicine Specialist, Phuket Island Rehab.
SSRIs and SNRIs are two related classes of antidepressant medication, used to treat depression, anxiety, and some other conditions, and they work in similar but slightly different ways. SSRI stands for selective serotonin reuptake inhibitor: these medications increase the level and activity of serotonin, a brain chemical (neurotransmitter) involved in mood, by blocking its reabsorption (reuptake). SNRI stands for serotonin-norepinephrine reuptake inhibitor: these increase the activity of two brain chemicals, serotonin and norepinephrine (noradrenaline), by blocking the reuptake of both. So the main difference is that SSRIs act mainly on serotonin, while SNRIs act on both serotonin and norepinephrine. Both are effective, commonly used, and generally safe antidepressants, and they are not addictive in the way that some drugs are. Which one is better depends on the individual, as people respond differently, and both are used for similar conditions, with some differences in their specific uses and side effects. The choice between an SSRI and an SNRI is a medical decision made with a doctor, based on the person’s condition, symptoms, response, and other factors. If you have questions about your antidepressant, your doctor is the right person to advise you.
SSRIs and SNRIs: two related antidepressant classes
SSRIs and SNRIs are two related classes of antidepressant medication, widely used to treat depression, anxiety, and some other conditions. They are among the most commonly prescribed types of antidepressants, and they work in similar but slightly different ways, which is the source of the main difference between them. SSRI stands for selective serotonin reuptake inhibitor, and SNRI stands for serotonin-norepinephrine reuptake inhibitor. Both work by affecting the levels and activity of certain chemical messengers (neurotransmitters) in the brain that are involved in mood and other functions, but they differ in which neurotransmitters they act on. Because they are related and often used for similar conditions, people, and sometimes patients trying to understand their own treatment, may wonder about the difference between SSRIs and SNRIs, or which is better. Understanding how these two classes compare helps make sense of these common antidepressants.
This article explains what SSRIs and SNRIs are, how they differ, what they are used for, and why the choice between them is made with a doctor. The central message is that SSRIs act mainly on the brain chemical serotonin, while SNRIs act on both serotonin and norepinephrine (noradrenaline), that both are effective, commonly used, and generally safe antidepressants used for similar conditions (with some differences in specific uses and side effects), and that which one is best depends on the individual, so the choice is a medical decision made with a doctor. Understanding the difference between SSRIs and SNRIs can help people understand their own or a loved one’s treatment. It is also important to know that these medications are not addictive in the way some drugs are, though they should be stopped gradually under medical guidance rather than abruptly. This article provides general information and is not a substitute for your doctor’s advice about your own treatment; questions about your antidepressant should be directed to your doctor.
How SSRIs and SNRIs work and differ
To understand the difference between SSRIs and SNRIs, it helps to understand how they work. Both act on neurotransmitters, chemical messengers in the brain, that are involved in regulating mood (and other functions). A key concept is reuptake: after a neurotransmitter is released to send a signal between brain cells, it is normally reabsorbed (taken back up) into the cell that released it, which ends its action. Reuptake inhibitors work by blocking this reabsorption, so that more of the neurotransmitter remains active in the brain for longer, enhancing its effect. This is thought to help improve mood and relieve symptoms of depression and anxiety, though the full picture of how antidepressants work is complex.
The difference between SSRIs and SNRIs lies in which neurotransmitters they act on. SSRIs (selective serotonin reuptake inhibitors) act mainly and selectively on serotonin: they block the reuptake of serotonin, increasing its activity in the brain, and this is their primary action. Serotonin is a neurotransmitter closely involved in mood, among other things. SNRIs (serotonin-norepinephrine reuptake inhibitors) act on two neurotransmitters: they block the reuptake of both serotonin and norepinephrine (also called noradrenaline), increasing the activity of both. Norepinephrine is another neurotransmitter involved in mood, alertness, energy, and other functions. So the main difference is straightforward: SSRIs increase serotonin activity, while SNRIs increase the activity of both serotonin and norepinephrine. This dual action of SNRIs, affecting an additional neurotransmitter, is the key distinction, and it can lead to some differences in their effects, uses, and side effects, though both classes are effective antidepressants. Common examples of each exist (for instance, SSRIs include medicines such as sertraline, fluoxetine, citalopram, and escitalopram, while SNRIs include medicines such as venlafaxine and duloxetine), but the essential difference is in the neurotransmitters they target. Understanding this difference, serotonin only versus serotonin plus norepinephrine, is the core of understanding SSRIs versus SNRIs.
| Aspect | SSRIs / SNRIs |
|---|---|
| Full name | SSRI: selective serotonin reuptake inhibitor |
| Full name | SNRI: serotonin-norepinephrine reuptake inhibitor |
| Acts on | SSRIs: serotonin; SNRIs: serotonin AND norepinephrine |
| Both are | Effective, common, generally safe antidepressants |
| Used for | Depression, anxiety, and some other conditions |
| Choice between them | A medical decision, based on the individual |
Uses, side effects, and choosing between them
SSRIs and SNRIs are used for broadly similar conditions, with some differences. Both are used to treat depression and various anxiety disorders (such as generalised anxiety disorder, panic disorder, and others), and both are used for some other conditions too. There are some differences in their specific uses: for example, SNRIs, because they also affect norepinephrine, are sometimes used for certain conditions involving pain (some SNRIs are used to treat certain chronic pain or nerve pain conditions), and different individual medications within each class have their own specific approved uses. But in general, both SSRIs and SNRIs are mainstays in the treatment of depression and anxiety. As for side effects, both classes share many common side effects (such as nausea, especially when starting, sleep changes, sexual side effects, and others), reflecting their shared action on serotonin, but there can be some differences: SNRIs, because they also affect norepinephrine, may be somewhat more likely to affect things like blood pressure or cause certain effects related to that neurotransmitter. Both are generally considered safe and well-tolerated for most people, though, as with any medication, side effects and individual responses vary, and any concerns should be discussed with a doctor.
A key point is that which medication, an SSRI or an SNRI (or a specific drug within either class), is best depends on the individual, because people respond differently to antidepressants: a medication that works well for one person may not suit another, in terms of both effectiveness and side effects. Because of this, the choice between an SSRI and an SNRI, and the choice of a specific medication, is a medical decision made with a doctor, based on factors such as the person’s specific condition and symptoms, their previous response to any medications, their other health conditions and medications, the side-effect profile, and other considerations. Often, SSRIs are used as a first choice for depression and anxiety, with SNRIs or other options considered if an SSRI is not effective or suitable, but this varies. Finding the right antidepressant can sometimes take some trial and adjustment, guided by the doctor. It is also important to note that antidepressants like SSRIs and SNRIs are not addictive in the way some drugs are; they do not cause cravings or compulsive use. However, they should not be stopped suddenly, especially after longer-term use, as this can cause discontinuation symptoms, so stopping should be done gradually under medical guidance. The key messages are that SSRIs act mainly on serotonin while SNRIs act on both serotonin and norepinephrine, that both are effective, commonly used antidepressants for similar conditions with some differences in uses and side effects, and that the choice between them is an individualised medical decision. If you have questions about your antidepressant, your doctor is the right person to advise you.
Summary
SSRIs and SNRIs are two related classes of antidepressant medication, used to treat depression, anxiety, and some other conditions, and they work in similar but slightly different ways. SSRI stands for selective serotonin reuptake inhibitor: these medications increase the level and activity of serotonin, a brain chemical involved in mood, by blocking its reabsorption (reuptake). SNRI stands for serotonin-norepinephrine reuptake inhibitor: these increase the activity of two brain chemicals, serotonin and norepinephrine (noradrenaline), by blocking the reuptake of both. So the main difference is that SSRIs act mainly on serotonin, while SNRIs act on both serotonin and norepinephrine. Both are effective, commonly used, and generally safe antidepressants, and they are not addictive in the way that some drugs are. Which one is better depends on the individual, as people respond differently, and both are used for similar conditions, with some differences in their specific uses and side effects. The choice between an SSRI and an SNRI is a medical decision made with a doctor, based on the person’s condition, symptoms, response, and other factors. If you have questions about your antidepressant, your doctor is the right person to advise you.
As Dr. Ponlawat Pitsuwan, addiction medicine specialist at Phuket Island Rehab, puts it, “The difference between an SSRI and an SNRI is actually quite simple at its core: an SSRI works mainly on serotonin, and an SNRI works on serotonin plus a second chemical, norepinephrine. That extra target gives SNRIs a slightly different flavour, sometimes useful for certain pain conditions, sometimes a bit more effect on things like blood pressure. But I always tell patients not to get too caught up in which class is theoretically better, because the honest truth is that people’s brains respond individually, and finding the right antidepressant is often a bit of careful trial and adjustment with your doctor. What matters is that both are effective, both are non-addictive, and neither should be stopped abruptly. If your antidepressant is on your mind, that is a conversation to have with your prescriber.”
Frequently asked questions
What is the main difference between SSRIs and SNRIs?
The main difference between SSRIs and SNRIs is which brain chemicals (neurotransmitters) they act on. SSRIs (selective serotonin reuptake inhibitors) act mainly and selectively on serotonin: they block the reuptake (reabsorption) of serotonin, increasing its activity in the brain. SNRIs (serotonin-norepinephrine reuptake inhibitors) act on two neurotransmitters: they block the reuptake of both serotonin and norepinephrine (also called noradrenaline), increasing the activity of both. So SSRIs increase serotonin activity, while SNRIs increase the activity of both serotonin and norepinephrine. Serotonin and norepinephrine are both neurotransmitters involved in mood (and other functions), and this difference in which chemicals they target, serotonin only for SSRIs versus serotonin plus norepinephrine for SNRIs, is the core distinction between the two classes. This dual action of SNRIs can lead to some differences in their effects, uses, and side effects, though both are effective antidepressants used for similar conditions (mainly depression and anxiety). Beyond this key difference in mechanism, both classes work by the same general principle of blocking neurotransmitter reuptake to enhance its effect. Understanding this difference, serotonin only versus serotonin plus norepinephrine, is the essence of understanding SSRIs versus SNRIs. The choice between them for a given person is a medical decision.
Are SSRIs or SNRIs better?
Neither SSRIs nor SNRIs are universally better; which is better depends on the individual, because people respond differently to antidepressants. Both SSRIs and SNRIs are effective, commonly used, and generally safe antidepressants, and both are used to treat similar conditions (mainly depression and anxiety). A medication that works well for one person may not suit another, in terms of both how effective it is and its side effects, so there is no single answer to which class is better in general. The best choice for a particular person depends on factors such as their specific condition and symptoms, their previous response to any medications, their other health conditions and medications, the side-effect profile, and other considerations, and it is a medical decision made with a doctor. Often, SSRIs are used as a first choice for depression and anxiety, with SNRIs or other options considered if an SSRI is not effective or suitable, but this varies by individual and situation. SNRIs’ additional action on norepinephrine can make them useful for certain situations, such as some pain conditions, but does not make them better overall. Finding the right antidepressant can sometimes involve some trial and adjustment with the doctor. So rather than one class being better, the right medication is the one that works best for the individual, which is determined through medical guidance. If you have questions about whether an SSRI or SNRI is right for you, your doctor can advise based on your specific situation.
What conditions do SSRIs and SNRIs treat?
SSRIs and SNRIs are used to treat broadly similar conditions, with some differences. Both are used mainly to treat depression and various anxiety disorders, such as generalised anxiety disorder, panic disorder, social anxiety disorder, and others; they are mainstays in the treatment of depression and anxiety. Both are also used for some other conditions: for example, they may be used in the treatment of obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and certain other mental health conditions, depending on the specific medication. There are some differences in their specific uses: SNRIs, because they also affect norepinephrine, are sometimes used for certain conditions involving pain, some SNRIs are used to treat certain chronic pain or nerve pain conditions, in addition to depression and anxiety. Different individual medications within each class also have their own specific approved uses. So while there is much overlap, with both classes used primarily for depression and anxiety, there are some differences in the range of conditions each is used for, particularly SNRIs’ use in some pain conditions. The specific condition being treated is one of the factors a doctor considers when choosing between an SSRI, an SNRI, or a particular medication. If you are wondering which is appropriate for a particular condition, this is a matter for medical advice, as the choice depends on the individual and their specific situation.
Do SSRIs and SNRIs have different side effects?
SSRIs and SNRIs share many common side effects but can also have some differences. Because both act on serotonin, they share many of the same common side effects, such as nausea (especially when first starting), changes in sleep or appetite, headache, sexual side effects, and, when starting or changing the dose, a temporary period of adjustment. However, there can be some differences: SNRIs, because they also affect norepinephrine, may be somewhat more likely to affect things influenced by that neurotransmitter, for example, they may be more likely to raise blood pressure or cause certain effects such as sweating or increased heart rate in some people. Both classes can, rarely, be associated with more serious effects, and there are some shared considerations, such as the risk of serotonin syndrome if combined with other serotonin-affecting drugs, and the importance of not stopping suddenly (to avoid discontinuation symptoms). Individual medications within each class also have their own particular side-effect profiles, and, importantly, side effects and how well a medication is tolerated vary from person to person. Both SSRIs and SNRIs are generally considered safe and well-tolerated for most people, and many side effects are mild or settle with time, but any troublesome or concerning side effects should be discussed with a doctor. The side-effect profile is one of the factors considered when choosing between an SSRI and an SNRI. So while there is much overlap, there are some differences in side effects, and individual response varies, which is why medical guidance is important.
Are SSRIs and SNRIs addictive?
No, SSRIs and SNRIs are not addictive in the way that substances like opioids, benzodiazepines, or stimulants are. They do not cause the cravings, compulsive use, or drug-seeking behaviour that define addiction, and they do not produce a high. This is an important point, because people sometimes worry that needing to be careful when stopping an antidepressant means it is addictive, but that is not the case. What can happen with antidepressants is that, after taking them for a while, the body adjusts to the medication, and stopping (especially abruptly, after longer-term use) can cause temporary discontinuation symptoms as the body readjusts, such as dizziness, flu-like feelings, mood changes, and unusual sensations. This is a physical readjustment, not addiction, and it does not involve craving the drug or losing control over its use. To avoid discontinuation symptoms, antidepressants should not be stopped suddenly but reduced gradually under medical guidance when the time is right to stop. So while SSRIs and SNRIs should be stopped carefully and gradually, and while the body can become physically adjusted to them, they are not addictive. This is reassuring for people who need these medications for depression, anxiety, or other conditions. If you are taking an SSRI or SNRI and are thinking about stopping, or have concerns, you should discuss it with your doctor rather than stopping on your own, so it can be done safely.
How is the choice between an SSRI and SNRI made?
The choice between an SSRI and an SNRI (and the choice of a specific medication within either class) is a medical decision made with a doctor, based on the individual’s situation, because people respond differently to antidepressants and there is no one-size-fits-all answer. The doctor considers factors such as the person’s specific condition and symptoms (for example, whether there are particular features or co-existing conditions, such as certain pain conditions that might favour an SNRI), their previous response to any antidepressants (what has or has not worked before), their other health conditions and medications (to avoid interactions or medications unsuitable for them), the side-effect profile of each option (and which side effects the person is more or less able to tolerate), and other considerations, including the person’s preferences. Often, an SSRI is used as a first choice for depression and anxiety, with an SNRI or another option considered if an SSRI is not effective or suitable, but this varies. Because individual response varies, finding the right antidepressant can sometimes involve some trial and adjustment, with the doctor monitoring the response and adjusting as needed. The important thing is that this choice, and any changes to antidepressant treatment, should be made with a doctor, who can weigh all these factors and guide the person to the most suitable medication for them. If you are starting, changing, or have questions about an antidepressant, your doctor is the right person to make this decision with you, tailored to your individual needs.
Sources
National Library of Medicine (MedlinePlus). Antidepressants. https://medlineplus.gov/antidepressants.html
National Institute of Mental Health (NIMH). Mental Health Medications. https://www.nimh.nih.gov/health/topics/mental-health-medications
National Health Service (NHS). SSRIs and SNRIs (Antidepressants). https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/
U.S. Food and Drug Administration (FDA). Antidepressant Medications. https://www.fda.gov/drugs
American Psychiatric Association (APA). Depression and Treatment. https://www.psychiatry.org/patients-families/depression
National Library of Medicine (MedlinePlus). Serotonin Syndrome. https://medlineplus.gov/ency/article/007272.htm
Difference between SSRIs and SNRIs — key entities and related terms
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