SNRIs vs. SSRIs: How They Work & Key Differences

What Are Reuptake Inhibitors?

Reuptake inhibitors are a type of antidepressant commonly used to treat symptoms of depression and anxiety.¹ They’re also sometimes prescribed for post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and bulimia.^2,3 The most common types of reuptake inhibitors are selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

SSRIs and SNRIs include medications used to treat depression and anxiety, such as sertraline (Zoloft), escitalopram (Lexapro), venlafaxine (Effexor), and duloxetine (Cymbalta). They stop the reuptake, or reabsorption, of important neurotransmitters, increasing the amount available in the brain.^2,3 This improves mood and decreases symptoms of anxiety and depression.

What’s the Difference Between SSRIs and SNRIs?

SSRIs and SNRIs impact neurotransmitters in the body differently. SSRIs affect serotonin, while SNRIs affect both serotonin and norepinephrine.^2,3 Serotonin affects mood, sleep, movement, and sexual desire.⁴ Norepinephrine is involved in the stress response.⁵

The main difference between SSRIs and SNRIs is that SNRIs work on two neurotransmitters, while SSRIs only work on serotonin. These medications are similar in their ability to improve mood and anxiety, but they don’t produce immediate results. It may take four to six weeks for them to build up in your system and for you to begin to feel their effects.¹

How Do SNRIs and SSRIs Work?

Reuptake inhibitors like SSRIs and SNRIs affect the reabsorption of certain neurotransmitters, which allows more of these neurotransmitters to build up in the body. This is responsible for the improvement in mood and anxiety symptoms that many people who take these medications experience.

How Do SSRIs Work?

SSRIs work by increasing serotonin in the brain.² Serotonin acts like a messenger that carries signals between nerve cells. After a message is carried, serotonin is reabsorbed by the nerve cells. SSRIs impede this process, which is called “reuptake.” This allows for more serotonin to be available, helping to improve mood and anxiety.

Common SSRI medications include:²

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Paroxetine (Paxil)
• Fluvoxamine (Luvox)
• Vilazodone (Viibryd) – which has additional effects on serotonin besides being reuptake inhibitor

How Do SNRIs Work?

SNRIs work similarly to SSRIs; the main difference is that SNRIs prevent the reuptake of both serotonin and norepinephrine.³ This allows for more of these chemicals to work in the brain, which helps regulate mood and may also reduce physical pain.

Common SNRI medications include:³

• Venlafaxine (Effexor)
• Duloxetine (Cymbalta)
• Desvenlafaxine (Pristiq)
• Milnacipran (Savella) – which is approved for the treatment of fibromyalgia, not depression
• Levomilnacipran (Fetzima)

Conditions SNRIs & SNRIs Treat

SSRIs and SNRIs are typically prescribed to treat depressive and anxiety disorders.^2,3 SNRIs are also sometimes prescribed for pain, arthritis, and neuropathy. SSRIs are usually the first line of treatment for depression because they offer the greatest benefit-to-risk ratio.⁶ If a person does not respond well or cannot tolerate an SSRI, then an SNRI or another type of antidepressant may be prescribed.

Conditions that SSRIs generally treat include:²

• Mood disorders, such as major depression, bipolar disorder, and premenstrual dysphoric disorder (PMDD)
• Anxiety disorders, such as generalized anxiety, social anxiety, and panic disorder
• Bulimia nervosa
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Conditions that SNRIs generally treat include:³

• Mood disorders, such as major depression
• Anxiety disorders, such as generalized anxiety, social anxiety, and panic disorder
• Muscle, joint, and bone pain
• Fibromyalgia
• Osteoarthritis
• Diabetic neuropathy

Side Effects of Taking an SSRI vs. SNRI

SSRIs and SNRIs may cause mild side effects, like nausea, decreased energy, sweating, and changes in libido.^7,8 Both are generally considered safe and believed to cause less severe side effects than other antidepressant medications, like tricyclics and MAOI inhibitors.⁹ While many of the risks and side effects of SSRIs and SNRIs are similar, SNRIs are more likely to cause cardiovascular side effects, like high blood pressure.

Common side effects of both SSRIs and SNRIs include:^7,8,9

• Nausea
• Fatigue
• Sexual problems
• Difficulty sleeping
• Sweating
• Weight gain

Additional side effects SNRIs may cause include:^7,8,9

• Vomiting
• Constipation
• Dry mouth
• Dizziness
• Palpitations
• High blood pressure

Serotonin syndrome can also occur while taking SSRIs and SNRIs.¹⁰ It occurs when there is too much serotonin in the body. It is a dangerous condition that requires medical intervention. Symptoms of serotonin syndrome include rapid heart rate, shivering, tremor, dilated pupils, excessive sweating, muscle jerking, and overactive reflexes.

More severe symptoms can include pressured speech, high body temperature, rapid changes in pulse and blood pressure, extreme confusion, and seizures. Other rare but serious side effects of SSRIs and SNRIs include unusual bleeding, bruising, and seizures. If you experience any of these side effects, seek medical attention right away.

Is an SSRI vs. SNRI More Effective at Treating Symptoms?

SSRIs and SNRIs are both effective at reducing depressive and anxiety symptoms.^2,3 There is mixed opinion on whether SSRIs or SNRIs as a group are more effective at treating symptoms.¹¹ Some studies have found that venlafaxine (Effexor) and duloxetine (Cymbalta) are more effective than certain SSRIs, but many of these studies have limitations and this has not been definitively proven.

Presently, one group of medications isn’t deemed more effective than another. Many providers will start a patient on an SSRI first, and prescribe an SNRI if the patient doesn’t respond well to the initial SSRI or cannot tolerate its side effects. Whether or not to prescribe an SSRI or SNRI is at the discretion of each provider.

Before prescribing, a provider will consider your symptoms, what medications you have tried in the past and your response to them, and how your family members have responded to medication to determine what type of antidepressant is right for you.

What to Do if Your SSRI or SNRI Isn’t Working

It can take approximately four to six weeks to feel the effects of SSRIs and SNRIs.¹ During the first few weeks, you may question whether your antidepressants are working. If you do not notice a change in your symptoms after at least six weeks, then you should talk to your prescriber. They may adjust your dose or try another medication.

How to Determine Which Medication Is Best for You

Your prescriber will gather information about your mental health symptoms and history, any treatments you have tried, family history of mental health and treatment, and your lifestyle. Once your provider has all of this information, they will be able to determine whether medication is right for your condition and, if so, what kind of medication.

It may be safe for you to take certain antidepressants while pregnant or breastfeeding. Your prescriber will talk to you about the risks and benefits and help you decide whether it’s right for you.

Questions your prescribing doctor may ask you prior to prescribing an SNRI vs. SSRI include:

1. What are your symptoms and for long have you been experiencing them?
2. What medications have you tried in the past and were they helpful?
3. Have you ever been in therapy?
4. Have any of your family members been treated on medications and what were their experiences?
5. Do you consume alcohol, tobacco, or drugs?
6. Are you pregnant or breastfeeding or planning to become pregnant?
7. Are you taking any other medications?
8. How can I compare SSRI and SNRI medications, such as Effexor vs Lexapro?

Questions to Ask Your Health Team About SSRI vs. SNRI

Before starting an SSRI or SNRI, you may be wondering how to take the medication, how to manage side effects, and what to avoid. It can help to write down your questions before your appointment and bring them with you.

Here are some questions to ask your care team about taking SNRIs vs. SSRIs:

• What type of medications is more effective for my symptoms?
• How much and how often should I take the medication?
• What are the most common side effects of the medication?
• Can this medication cause severe side effects?
• What should I do if I experience side effects?
• Are there any medications or substances that I should avoid?
• Is this medication safe to take while pregnant or breastfeeding?
• What should I do if I want to stop taking the medication?

If you experience severe side effects and cannot get in contact with your provider, call 9-1-1 right away. If you experience suicidal thoughts, call 9-1-1 or the National Suicide Prevention Lifeline at 800-273-8255.

Final Thoughts On SSRIs vs. SNRIs

Both SSRIs and SNRIs can be effective for treating depression, anxiety, and other conditions. Your healthcare team can talk to you about the benefits of each type of medication and help determine which one is right for you.