Differences and How They Work

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are two of the most common types of medications used to treat conditions such as depression, anxiety disorders, and obsessive-compulsive disorder. Both are known as reuptake inhibitors.

These medications work by increasing levels of brain chemicals called neurotransmitters, which communicate signals between neurons (nerve cells). While SSRIs and SNRIs are used to treat similar conditions, there are some key differences between them, including which specific neurotransmitters they affect.

This article will explain how the medications work, when they’re prescribed, their side effects, and their differences.

What Are SSRIs and SNRIs?

Neurotransmitters play a role in our moods, memory, focus, social interaction, sexual function, and other important aspects of human life. An imbalance or dysfunction of certain neurotransmitters is believed to affect mental health and is associated with several conditions, such as depression and anxiety.

Reuptake inhibitors help regulate neurotransmitters by blocking their reabsorption. Reabsorption takes place after a signal has been transmitted in the brain. Once the neurotransmitter has completed its task, it is reabsorbed back into the neuron.

When neurotransmitter levels are low enough to affect normal functioning, reuptake inhibitors can help increase their concentration and availability by preventing them from being reabsorbed.

Different neurotransmitters affect different functions of the brain. The main neurotransmitters associated with mental health include:

• Serotonin: Involved in functions such as sleep, memory, appetite, mood, and more
• Dopamine: Involved in many functions, including motor control, reward and reinforcement, and motivation
• Norepinephrine: Involved in readying the body for action and increasing alertness, focus, and memory retrieval

SSRIs and SNRIs, the two main reuptake inhibitors, are similar in many ways, but the the medications do have distinct differences.

Difference Between SSRIs and SNRIs

SSRIs work by blocking the reuptake of serotonin, while SNRIs block the uptake of both serotonin and norepinephrine. SSRIs are typically the first choice of medication prescribed for conditions like depression and anxiety because they have fewer side effects.

SSRI medications include:

• Celexa (citalopram)
• Lexapro (escitalopram)
• Luvox (fluvoxamine)
• Paxil (paroxetine)
• Prozac (fluoxetine)
• Zoloft (sertraline)

SNRI medications include:

• Cymbalta (duloxetine)
• Effexor (Venlafaxine)
• Fetzima (levomilnacipran)
• Pristiq (desvenlafaxine)
• Savella (milnacipran)

Neither SSRIs nor SNRIs are inherently better than the other. Which medication works best varies based on the individual and the condition it is used for.

Uses of SSRIs vs. SNRIs

SSRIs and SNRIs are used to treat various mental health conditions. They are sometimes also used to treat other types of medical problems such as pain disorders or gastrointestinal conditions. Your healthcare provider may start you on one type of medication and switch to another one or alter the dose depending on how well it works for you and any side effects you experience.

SSRI Uses

SSRIs are most commonly used in treating:

They may also be used to treat other conditions such as:

SNRI Uses

The SNRI used depends on the condition being treated. The following medications are often prescribed for particular disorders:

Cymbalta (duloxetine)

Effexor (Venlafaxine)

• Major depressive disorder
• Generalized anxiety disorder
• Panic disorder
• Social phobia

Fetzima (levomilnacipran)

• Major depressive disorder

Pristiq (desvenlafaxine)

• Major depressive disorder

Savella (milnacipran)

Before Prescribing

Reuptake inhibitors may be prescribed by a primary healthcare provider or a mental health professional who can prescribe medications, such as a psychiatrist.

Before prescribing an SSRI or an SNRI, your healthcare provider will consider and discuss several factors with you, including:

• Current symptoms and diagnosis
• Your age
• Medical history, including if you have had these symptoms before
• Treatment history, including if previous medications worked well or didn’t work well in the past
• Family history and whether a certain medication has worked well for a close family member
• Current overall health, to rule out medications that may not be appropriate for people who have other health considerations
• Lifestyle, including your diet and alcohol or recreational drug use
• If you are pregnant or plan to become pregnant
• Potential side effects of each medication
• If the dosing schedule is feasible/convenient
• Whether you can afford the cost of the medication
• The healthcare provider’s experience and history prescribing each medication

Your healthcare provider may order blood tests or other tests to check for other medical considerations that could influence which medication is most appropriate.

Once a medication is chosen, your healthcare provider will usually begin by prescribing a low dose and increase the dosage over time if needed.

It can take from two weeks to two months for the benefits of the medication to take full effect. Your healthcare provider will likely schedule a follow-up within a few weeks to check in on how the treatment is going and if there are side effects. They may advise continuing with the same medication and dosage, changing the dosage, or switching to a different medication altogether.

Dosage of SSRIs vs. SNRIs

Dosages for SSRIs and SNRIs vary depending on the medication, the condition being treated, and the person taking it.

Always check with your healthcare provider about proper dosing, and never change doses without first discussing it with your healthcare provider.

SSRI Dosages

• Celexa (citalopram): Comes in 10 mg, 20 mg, and 40 mg tablets; oral solution available as 10mg/5mL
• Lexapro (escitalopram): Comes in 5 mg, 10 mg, and 20 mg tablets, and a 1 mg per milliliter (mL) oral solution
• Luvox (fluvoxamine): Comes in 25 mg, 50 mg, and 100 mg immediate-release tablets, and 100 mg and 150 mg extended-release capsules
• Paxil (paroxetine): Comes in 10 mg, 20 mg, 30 mg, and 40 mg tablets. Each 5 mL of oral solution contains paroxetine hydrochloride equivalent to paroxetine, 10 mg. Extended-release tablet strengths include 12.5 mg, 25 mg, and 37.5 mg. A 7.5 mg capsule is available only for hot flashes associated with menopause.
• Prozac (fluoxetine): Comes in 10 mg, 20 mg, and 40 mg capsules, and a 90 mg delayed release capsule taken weekly; oral solution available as 20mg/5mL
• Zoloft (sertraline): Comes in 25 mg, 50 mg, and 100 mg tablets, and an oral solution of 20 mg/mL

SNRI Dosages

• Cymbalta (duloxetine): Comes in 20 mg, 30 mg, 40 mg, and 60 mg capsules
• Effexor (Venlafaxine): Comes in 37.5 mg, 75 mg, and 150 mg extended-release tablets; immediate-release tablets available in 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg
• Fetzima (levomilnacipran): Comes in 20 mg, 40 mg, 80 mg, and 120 mg extended-release capsules
• Pristiq (desvenlafaxine): Comes in 25 mg, 50 mg, and 100 mg tablets
• Savella (milnacipran): Comes in 12.5 mg, 25 mg, 50 mg, and 100 mg tablets

How to Take and Store

It is important to take reuptake inhibitors as prescribed and avoid missing a dose. If you miss a dose, try to take it as soon as you remember, unless it’s almost time to take your next dose, in which case you should skip the missed dose. You should not take a double dose to “make up” for the one you missed.

Taking reuptake inhibitors with food may help prevent nausea.

Unless otherwise specified, these medications should be:

• Kept in the original container
• Stored at room temperature away from moisture and heat (e.g., not in the bathroom or kitchen)

Keep medication out of reach and sight of children. 

Side Effects of SSRIs vs. SNRIs

The side effects of SSRIs and SNRIs typically happen at the beginning of treatment and often lessen over time. Your healthcare provider will prescribe a medication with these side effects in mind.

The common side effects of SSRIs and SNRIs include:

SSRIs

SNRIs

• Headaches
• Dizziness
• Nausea
• Heavy sweating
• Dry mouth
• Constipation
• Insomnia
• Sexual difficulties (low sex drive, inability to have an orgasm, erectile dysfunction)

If the side effects are concerning or intolerable, talk with your healthcare provider to see if adjustments can be made.

Warnings and Interactions

Some things should be avoided or approached with caution when taking SSRIs or SNRIs, including:

• Alcohol: Alcohol can make depression symptoms worse. When combined with antidepressants, it can make someone more intoxicated with less alcohol. It also lowers inhibition and has been linked to suicide.
• Marijuana: Marijuana is associated with depression, but it is unknown if it causes depression. Many healthcare providers believe that marijuana use interferes with the benefits of antidepressants.
• Driving: Antidepressants can cause drowsiness in some people, particularly at the beginning of treatment. If you feel drowsy, avoid driving.
• Pregnancy: While the use of antidepressants in pregnancy may present potential risks to the baby (especially during the early stages), there are also potential risks to the baby if depression goes untreated. Consult with your healthcare provider about the benefits and risks of taking antidepressants during pregnancy, as well as the appropriateness of any non-medication treatment options.

SSRIs should be used with caution as a treatment for bipolar disorder as they may exacerbate rapid mood cycling.

Suicidality

In 2004, the FDA issued a boxed warning on SSRIs regarding their use in children and teens. A warning is still included in the package inserts for all antidepressants in common use, discussing the risk of suicidal thoughts, hostility, and agitation in children, teens, and young adults.

Anyone on antidepressants, particularly those under age 25, should be mindful of the potential for suicidal thoughts and actions, and seek help immediately if they notice signs or experience such thoughts.

Stopping Reuptake Inhibitors

You should not stop taking your medication abruptly or miss several doses. Doing so can cause unpleasant side effects.

It is important to discuss any changes, including stopping medication use, with your healthcare provider. If you want to stop taking your medication or change to a different one, always do so under the guidance of a healthcare provider who can help you wean off them safely.

Summary

SSRIs and SNRIs are medications that increase the levels of certain neurotransmitters in your brain. They are often prescribed to treat depression and other mental health conditions. 

SSRIs block the absorption of serotonin, while SNRIs block the absorption of serotonin and norepinephrine. SSRIs are usually prescribed first since they tend to have fewer side effects.

Talk to your healthcare provider about any side effects you might experience while taking these medications, and always follow your healthcare provider’s instructions for dosage. Don’t stop taking any of these medications without talking to your healthcare provider.