SSRI Alternatives: Other Options for Treating Depression

Daniel Lieberman

Reviewed by Daniel Z. Lieberman, MD

Written by Rachel Sacks

Published 04/22/2022

Updated 11/16/2023

The world of depression treatment options is vast, varied and confusing at times. So many antidepressant medications, so many types of therapy, so many acronyms and so much information.

In all the noise about the treatment of depression, you may keep hearing these four letters: SSRI. Or maybe you’re more familiar with the names Lexapro®, Zoloft® or Prozac®.

For most people with depression or anxiety, SSRIs — also known as selective serotonin reuptake inhibitors — are a safe, effective form of treatment that produces real, noticeable results. This makes them a very commonly used type of antidepressant.

But at the risk of sounding like a helicopter parent or like we’re back in middle school, SSRIs may be popular, but that doesn’t mean they’re the right choice for everyone. Fortunately, you’re a smart adult who cares about your mental health (it’s why you’re here, after all!) and you know that your treatment may look different from others’ treatments.

So what non-SSRI antidepressants or non-SSRI anxiety meds are out there? We’ll talk not only about alternatives to SSRIs but the alternatives to antidepressant medication in general. 

So, breathe a sigh of relief, because you don’t have to try and sift through all the information out there on Lexapro or Zoloft alternatives yourself.

If you currently use an SSRI, you’re not alone — SSRIs and other antidepressants are so common that between 2015 and 2018, over 13 percent of adults used an antidepressant. There’s no shame in using an antidepressant, and there’s certainly no shame in wanting an alternative to a common antidepressant such as an SSRI. Everyone’s mental health treatment looks different.

Often prescribed for major depressive disorder, SSRIs are also FDA-approved for anxiety disorders. Not-so-fun fact time: it’s not uncommon for people with anxiety to also have depression, with nearly half of those diagnosed with depression also having an anxiety disorder.

Before we start exploring alternatives to SSRIs, a quick rundown on how they’re believed to work. Selective serotonin reuptake inhibitors essentially stop your brain from reabsorbing serotonin, a key neurotransmitter (or brain chemical) associated with mood.

Most SSRIs are generally safe and effective, and they’re considered the first-line treatment for depression and many other mood disorders. But that doesn’t mean they’re always the best option for you in particular. 

The common downsides of SSRIs?

  • Side effects. SSRIs are generally less likely to cause side effects than older antidepressants, but adverse effects still happen for some people. Common SSRI side effects include nausea, agitation, anxiety, dizziness and more. These are temporary and mild in most cases, but may persist or become severe for some people.

  • Drug interactions. SSRIs can interact with other antidepressants, blood thinning medications, nonsteroidal anti-inflammatory drugs (NSAIDs) and other medications. SSRIs can also cause a dangerous reaction called serotonin syndrome when used with other serotonin-affecting drugs.

  • Withdrawal symptoms. Abruptly stopping medications like SSRIs or other antidepressants can lead to withdrawal symptoms. While the withdrawal symptoms of each medication may vary, you can get an idea of what they might entail from this article on Zoloft withdrawal.

  • Suicide risk. Although there’s some scientific controversy about the potential suicide risk of antidepressants, SSRIs and other antidepressants come with an FDA warning that they may cause suicidal thoughts or behavior in young people aged 24 and under. It’s worth noting that this warning can be found on all antidepressants, not only SSRIs, meaning that using one antidepressant over another may not affect the risk of suicidal actions.

There’s also the possibility that SSRIs just are not effective for you and you experience a return of your depression symptoms — a common occurrence that’s known as “breakthrough depression” and affects a third of people who use antidepressants.

Whether symptoms of depression like a persistent low mood or chronic fatigue come back or you start having sleep or appetite issues, this could be a sign to switch to an SSRI alternative.

If you’re at risk for any of the issues listed above, using an SSRI may not be the best or most effective option for you. However, if you’re currently prescribed an SSRI, always check with your healthcare provider before making any changes to your current medication usage.

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Just because they’re a common treatment doesn’t mean SSRIs are the only treatment option for depression and anxiety disorders. There are plenty of non-SSRI antidepressants, as well as alternatives to antidepressants, out there, from different types of medications to therapy and lifestyle changes.

Curious what some alternatives to Zoloft are? Or maybe you’re looking for a different anxiety medication. Keep reading for more information on:

  • SNRIs

  • Bupropion

  • TCAs

  • MAOIs

  • Benzodiazepines

  • Buspirone

Don’t worry, we’ll explain what all the acronyms stand for, how these medications work and more.

Non-SSRI Antidepressants

Depression and anxiety symptoms come in all different forms — and so do their treatments. If SSRIs aren’t working for you or you’re interested in other medication options, your healthcare provider might suggest:

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs). Another common type of antidepressant, SNRIs work in a similar way to SSRIs by increasing both serotonin and another neurotransmitter called norepinephrine. Common SNRIs include venlafaxine (sold as Effexor®), duloxetine (Cymbalta®) and desvenlafaxine (Pristiq®). For some people, SNRIs cause more side effects that SSRIs, so it’s generally best to start with an SSRI.

  • Bupropion. Sold as Wellbutrin® or Wellbutrin XL®, bupropion is referred to as an atypical antidepressant, and it affects the neurotransmitters norepinephrine and dopamine. Bupropion is often used as an alternative to SSRIs or as a secondary medication in combination with an SSRI or SNRI because it’s less likely to cause sexual side effects. Although bupropion is an excellent medication for depression, unlike SSRIs and SNRIs, it doesn’t treat anxiety disorders.

  • Tricyclic antidepressants (TCAs). An older type of antidepressant, TCAs also alter your levels of neurotransmitters. Tricyclic antidepressants aren’t used as often today because they can cause more side effects and drug interactions than newer medications. Despite their side effect risk, they’re still very occasionally prescribed to treat depression when other medications don’t work.

  • Monoamine oxidase inhibitors (MAOIs). Another group of older antidepressants, MAOIs don’t work by targeting specific neurotransmitters. Instead, they target the enzyme monoamine oxidase, which is responsible for controlling a variety of neurotransmitters in the brain. MAOIs are very rarely used today because of their very difficult side effects.

Non-SSRI Anxiety Medications

We all worry or feel anxious from time to time. But many people find their anxiety levels are at an all-time high, day in and day out. Generalized anxiety disorder (GAD), for example, is when someone has exaggerated worries about everyday things and will spend literal hours obsessing about these worries. Women are also twice as likely to have GAD — another really not-fun fact.

Whether you have GAD or another type of anxiety disorder, randomized controlled trials have shown that, in addition to SSRIs, SNRIs, benzodiazepines and other medications are effective for treating anxiety.

  • Benzodiazepines. Used to treat anxiety in the short-term, benzodiazepines provide relief from anxiety symptoms in as little as 30 minutes to one hour. They promote a relaxed feeling, which is why Xanax® is often used for sleep. However, this medication isn’t recommended for long-term use, as it can cause dependence, become less effective over time and lead to withdrawal symptoms when stopped. Commonly prescribed benzodiazepines include alprazolam (Xanax), clonazepam (Klonopin®), diazepam (Valium®) and lorazepam (Ativan®). If you find yourself needing to take a benzodiazepine more than once a month, you should talk to your provider about safer options.

  • Buspirone. Considered a modern anti-anxiety medication, buspirone (Buspar®) is less likely to cause side effects than other medications and has no associated risk of causing dependence or withdrawal symptoms if treatment is stopped abruptly. Buspirone is often prescribed as a second-line medication for people who don’t respond to SSRIs or experience side effects when using SSRIs to treat anxiety.


Medication is often only one part of the equation for the treatment of depression and anxiety disorders. Many conditions for which SSRIs are commonly prescribed are often also treated using psychotherapy.

Cognitive behavioral therapy (or CBT) is a common type of therapy and has a lot of evidence for its ability to help treat several mental health disorders — including depression and anxiety. In CBT, patients learn to identify and understand the thought processes and behaviors that can contribute to depression and anxiety symptoms.

Of course, depending on your unique needs, you may benefit from other types of therapy. Other forms of therapy used to treat depression, anxiety and other mental health conditions can include interpersonal therapy (IPT) and dialectical behavior therapy (DBT).

Sometimes, therapy alone may be enough to provide relief from depression and/or anxiety. But many people also need to combine a form of therapy for depression with an antidepressant medication listed above to treat their symptoms and work towards recovery.

Talking about what makes you anxious or the dark thoughts running through your head with a stranger may seem difficult at first. Luckily, we offer online therapy and other mental health resources to get you started from the comfort of your couch.

Lifestyle Changes

While medication may be the first thing you think of when it comes to depression or anxiety treatment, some simple lifestyle changes can make a surprising difference in your mental health journey.

Rather than being used instead of medication or psychotherapy, these healthy habits can be thought of as supplementary treatments. Talk to your healthcare provider about how certain lifestyle changes and new habits may fit into your treatment if you’re currently taking an antidepressant.

You can consider including regular exercise in your routine, eating a balanced diet, getting enough sleep, finding ways to reduce stress in your life, getting more sunlight and spending time with friends, family and other loved ones.

There are also some natural remedies for depression, such as herbal products and supplements, that may offer benefits.

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While SSRIs are commonly prescribed for depression and anxiety, there are plenty of reasons why people may be searching for alternatives.

  • SSRIs don’t work for everyone. They may cause uncomfortable side effects, or you may be at risk of experiencing drug interactions or withdrawal symptoms. You may also experience a return of your depression symptoms, known as “breakthrough depression.”

  • Non-SSRI antidepressant options are vast. There are plenty of alternative medications to treat depression or anxiety, such as SNRIs, TCAs, MAOIs or bupropion antidepressants that affect different chemicals in the brain.

  • So are the alternatives for anxiety. Medications like buspirone or benzodiazepines are also prescribed for anxiety symptoms, although the latter can lead to dependence and withdrawal symptoms.

  • Therapy can help too. Psychotherapy is an extremely efficient treatment for both anxiety and depression. Different types of therapy can help you identify unhealthy thoughts and behaviors that contribute to your symptoms. 

  • Healthy lifestyle changes have lots of mental and physical health benefits. While not a replacement for medication or therapy, healthy habits can help alleviate symptoms and improve your mood, among other benefits. Regular exercise, a healthy diet, plenty of sleep and spending time with loved ones can all make an impact.

If your SSRI isn’t working for you, make sure to talk to your healthcare provider before making any changes to your medication to keep yourself safe and prevent both withdrawal symptoms and your mental health symptoms from worsening You can also read our guide on switching antidepressants to learn more if you’re interested in changing medication.

You can use online psychiatry to get connected with a licensed psychiatrist or our mental health services to further talk about medication and therapy options.

20 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Daniel Z. Lieberman, MD

Dr. Daniel Z. Lieberman is the senior vice president of mental health at Hims & Hers and of psychiatry and behavioral sciences at George Washington University. Prior to joining Hims & Hers, Dr. Lieberman spent over 25 years as a full time academic, receiving multiple awards for teaching and research. While at George Washington, he served as the chairman of the university’s Institutional Review Board and the vice chair of the Department of Psychiatry and Behavioral Sciences.

Dr. Lieberman’s has focused on , , , and to increase access to scientifically-proven treatments. He served as the principal investigator at George Washington University for dozens of FDA trials of new medications and developed online programs to help people with , , and . In recognition of his contributions to the field of psychiatry, in 2015, Dr. Lieberman was designated a distinguished fellow of the American Psychiatric Association. He is board certified in psychiatry and addiction psychiatry by the American Board of Psychiatry and Neurology.

As an expert in mental health, Dr. Lieberman has provided insight on psychiatric topics for the U.S. Department of Health and Human Services, U.S. Department of Commerce, and Office of Drug & Alcohol Policy.

Dr. Lieberman studied the Great Books at St. John’s College and attended medical school at New York University, where he also completed his psychiatry residency. He is the coauthor of the international bestseller , which has been translated into more than 20 languages and was selected as one of the “Must-Read Brain Books of 2018” by Forbes. He is also the author of . He has been on and to discuss the role of the in human behavior, , and .


  • 1992: M.D., New York University School of Medicine

  • 1985: B.A., St. John’s College, Annapolis, Maryland

Selected Appointments

  • 2022–Present: Clinical Professor, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2013–2022: Vice Chair for Clinical Affairs, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2010–2022: Professor, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2008–2017: Chairman, George Washington University Institutional Review Board

Selected Awards & Honors

  • 2022: Distinguished Life Fellow, American Psychiatric Association

  • 2008–2020: Washingtonian Top Doctor award

  • 2005: Caron Foundation Research Award


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