Mental Health What to Know About SSRIs vs. SNRIs A side-by-side comparison to help you decide By Heather Jones Heather Jones Facebook Twitter Heather M. Jones is a freelance writer with a focus on health, parenting, disability, and feminism. Learn about our editorial process Published on August 10, 2021 Medically reviewed by David Snyder, PharmD, BCPP Medically reviewed by David Snyder, PharmD, BCPP LinkedIn David Snyder, PharmD, BCPP, is a board-certified clinical pharmacist and psychopharmacology expert at McLean Hospital in Belmont, Massachusetts. Learn about our Medical Expert Board Print Table of Contents View All Table of Contents What Are Reuptake Inhibitors? Uses Dosage Side Effects Warnings and Interactions Frequently Asked Questions A Word From Verywell Neurotransmitters are chemical messengers within the brain that communicate signals between neurons (nerve cells). They 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. Medications known as 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 cell that released it. Limiting the reuptake process increases the concentration and availability of neurotransmitters in the brain. Two of the most common reuptake inhibitors are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). While SSRIs and SNRIs are used to treat similar conditions, there are some key differences between them, including which specific neurotransmitters they affect. SDI Productions / Getty Images What Are Reuptake Inhibitors? Reuptake inhibitors are medications that influence the neurotransmitter and reabsorption process in the brain. When a person’s level of neurotransmitters is low enough to affect normal functioning, reuptake inhibitors 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 are: 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. An imbalance in these neurotransmitters is associated with several mental health conditions, including major depressive disorder, anxiety disorders, and mood disorders. The two main reuptake inhibitors are SSRIs and SNRIs. These medications are similar in many ways, but they do have distinct differences. SSRIs vs. SNRIs SSRIs block the reuptake of serotonin only. They 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) SNRIs, on the other hand, block the uptake of both serotonin and norepinephrine. 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 treating. Uses SSRIs SSRIs are most commonly used in treating: Depression Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Panic disorder Severe phobias such as agoraphobia and social phobia Bulimia Post-traumatic stress disorder (PTSD) Premenstrual dysphoric disorder (PMDD) They may also be used to treat other conditions such as: Premature ejaculation Premenstrual syndrome (PMS) Fibromyalgia Irritable bowel syndrome (IBS) SNRIs Which SNRI is used depends on the condition being treated. The following medications are often prescribed for particular disorders: Cymbalta (duloxetine) Major depressive disorder Generalized anxiety disorder Diabetic peripheral neuropathy Fibromyalgia Musculoskeletal pain Osteoarthritis Effexor (Venlafaxine) Major depressive disorder Generalized anxiety disorder Panic disorder Social phobia Fetzima (levomilnacipran) Major depressive disorder Pristiq (desvenlafaxine) Major depressive disorder Savella (milnacipran) Fibromyalgia Before Prescribing Reuptake inhibitors may be prescribed by a primary healthcare provider or a mental health professional who is able to prescribe medications, such as a psychiatrist. Before prescribing an SSRI or an SNRI, your healthcare provider will consider and discuss a number of factors with you, including: Current symptoms and diagnosisYour ageMedical history, including if you have had these symptoms beforeTreatment history, including if previous medications worked well or didn’t work well in the pastFamily history and whether a certain medication has worked well for a close family memberCurrent overall health, to rule out medications that may not be appropriate for people who have other health considerationsLifestyle, including your diet and alcohol or recreational drug useIf you are pregnant or plan to become pregnantPotential side effects of each medicationIf the dosing schedule is feasible/convenientWhether you can afford the cost of the medicationThe 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, change the dosage, or switch to a different medication altogether. Be Mindful of Possible Interactions Always inform your healthcare provider and pharmacist about any medications (prescriptions, over-the-counter, and herbal), supplements, and vitamins that you currently take.Potential interactions are not always obvious and have the potential to cause side effects, influence the effectiveness of the medications, or even be dangerous. Dosage 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. SSRIs Celexa (citalopram): Comes in 10 mg, 20 mg, and 40 mg tablets; oral solution available as 10mg/5mLLexapro (escitalopram): Comes in 5 mg, 10 mg, and 20 mg tablets, and a 1 mg per millilitre (mL) oral solutionLuvox (fluvoxamine): Comes in 25 mg, 50 mg, and 100 mg immediate release tablets, and 100 mg and 150 mg extended release capsulesPaxil (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/5mLZoloft (sertraline): Comes in 25 mg, 50 mg, and 100 mg tablets, and an oral solution of 20 mg/mL Serotonin Syndrome Too much serotonin can cause a condition called serotonin syndrome. This condition can range from mild to life threatening. It usually occurs when different medications that affect serotonin are taken together, but it can happen if SSRIs or SNRIs are taken in too high a dosage. Consult your healthcare provider if you experience the following symptoms: Nausea or vomiting Diarrhea Confusion Muscle rigidity Dilated pupils Shivers Very high temperature Seizures Irregular heartbeat If serotonin syndrome is suspected, seek medical attention immediately. SNRIs Cymbalta (duloxetine): Comes in 20 mg, 30 mg, 40 mg, and 60 mg capsulesEffexor (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 mgFetzima (levomilnacipran): Comes in 20 mg, 40 mg, 80 mg, and 120 mg extended release capsulesPristiq (desvenlafaxine): Comes in 25 mg, 50 mg, and 100 mg tabletsSavella (milnacipran): Comes in 12.5 mg, 25 mg, 50 mg, and 100 mg tablets Modifications Each individual medication has its own guidelines for ways in which it may or may not be modified. Consult your pharmacist or medication package insert for more specific details. 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 containerStored at room temperature away from moisture and heat (e.g., not in the bathroom or kitchen) Make sure medication is kept out of reach and sight of children. Side Effects 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 are: SSRIs Agitation Nausea Diarrhea Sexual difficulties (such as low sex drive, inability to achieve orgasm, erectile dysfunction) Dizziness Headaches Insomnia Increased anxiety Exhaustion Dry mouth Tremors 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 on 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 black box 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. Help Is Available If you or someone you know are having suicidal thoughts, dial 988 to contact the 988 Suicide & Crisis Lifeline and connect with a trained counselor. If you or a loved one is in immediate danger, call 911. For more mental health resources, see our National Helpline Database. 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 that you discuss any changes, including stopping medication use, with your healthcare provider. If you would like 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. Frequently Asked Questions Do SSRIs and SNRIs help with anxiety? Both SSRIs and some SNRIs help with anxiety. SSRIs are often prescribed as the first option, but both types of medications are effective for treating anxiety. Which one works best depends largely on the individual. Which antidepressant has the least side effects? SSRIs tend to have fewer side effects than SNRIs, but side effects of both medications vary greatly by the individual. Some may experience significant side effects from a medication, while others may experience none from the same one. The best thing you can do is work with your healthcare provider to find the best balance between effectiveness and side effects. How do neurotransmitters affect depression? If the brain has too low a concentration of certain neurotransmitters, such as serotonin, the person can experience symptoms of depression. Reuptake inhibitors prevent these neurotransmitters from being reabsorbed, which increases their concentration and availability. What is the difference between SSRIs and SNRIs? On the most basic level, SSRIs prevent the reuptake of serotonin, while SNRIs prevent the reuptake of serotonin and norepinephrine. A Word From Verywell Antidepressants are not one size fits all. Different medications, including different types of SSRIs and SNRIs, will work better for some, while a different type will work better for others. If you are experiencing symptoms that may benefit from reuptake inhibitors, meet with your healthcare provider to discuss options. Finding the right medication and the right dose can take time, and sometimes there is a bit of trial and error. Keep working with your healthcare provider until you find the best fit for you. 10 Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69(Suppl E1):4-7. National Health Service. Overview - SSRI antidepressants. Locher C, Koechlin H, Zion SR, et al. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents: a systematic review and meta-analysis. JAMA Psychiatry. 2017;74(10):1011. doi:10.1001/jamapsychiatry.2017.2432 Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014;11(3-4):37-42. American Academy of Family Physicians. How to safely take antidepressants. National Health Service. Dosage - selective serotonin reuptake inhibitors (SSRIs). Cleveland Clinic. Depression medications. National Health Service. Cautions - selective serotonin reuptake inhibitors (SSRIs). McGirr A, Vöhringer PA, Ghaemi SN, Lam RW, Yatham LN. 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. The Lancet Psychiatry. 2016;3(12):1138-1146. doi:10.1016/S2215-0366(16)30264-4 Pompili M, Serafini G, Innamorati M, et al. Antidepressants and suicide risk: a comprehensive overview. Pharmaceuticals. 2010;3(9):2861-2883. doi:10.3390/ph3092861 By Heather Jones Heather M. Jones is a freelance writer with a strong focus on health, parenting, disability, and feminism. 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