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Switching from Zoloft to Prozac: What to Expect

Daniel Lieberman

Reviewed by Daniel Z. Lieberman, MD

Written by Taylor Trudon

Published 04/21/2022

Updated 11/16/2023

Dealing with depression can feel overwhelming, whether you’re deep in a two-week funk or have been enduring it for years. And while depression is a mental health condition that looks different for everyone, it’s more common than you probably think — about 21 million American adults experienced a depressive episode in the last year. 

Sure, that statistic might seem a little grim at first glance, but there’s a light at the end of the tunnel.

Whether you have major depressive disorder (MDD) or seasonal affective disorder (SAD), depression is very treatable. One of the most effective treatments for depression — as well as anxiety disorders — is medication. This includes Zoloft® (which contains sertraline as the active ingredient) and Prozac® (which contains fluoxetine as its active ingredient).

When it comes to antidepressant medication like Zoloft® and Prozac®, what works best for you may not work for someone else, and vice versa.

If a healthcare provider diagnoses you with depression, you might need to try several types of antidepressants — potentially at different doses — until you find the right fit (just like Goldilocks).

For instance, you might start off taking Zoloft® but eventually switch to Prozac® because its side effects feel less severe. Whatever the reason, switching from one medication to another is totally normal.

That said, if you’re thinking about changing from Zoloft® to Prozac® — two of the most popular medication options for depression —  the process can be a little confusing. When is the right time to make the big switch? What are the risks? How do you go about it safely?

Of course, you should always consult a healthcare provider for medical advice before making any changes to your medication. But we’ll run through these questions and offer more insight into the process so you’re armed with the preliminary info. 

Let’s start with the basics: Zoloft® and Prozac® belong to a category of antidepressants called SSRIs, or selective serotonin reuptake inhibitors. They do their job by targeting a neurotransmitter called serotonin, also known as the “happy hormone.” 

Because of their effectiveness, both Zoloft® and Prozac® are considered first-line treatments for treating depression, as well as certain anxiety disorders. In addition to having the official seal of approval from the U.S. Food and Drug Administration for treating depression, both meds are FDA-approved to treat obsessive-compulsive disorder (OCD) and panic disorder

Their differences? Zoloft® can be used to help people with post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder. Prozac®, on the other hand, can be used as a treatment for bulimia nervosa. 

You might be thinking, These medications sound pretty similar — why would someone want to switch in the first place? 

It may seem confusing, given that Zoloft® and Prozac® share many similarities. This includes overlapping with certain common side effects, like: 

  • Diarrhea and dyspepsia (indigestion) 

  • Nausea

  • Tremors

  • Sweating

  • Decreased libido

  • Abnormal ejaculation

There are several other potential side effects that could be cause by both medications, but some of these side effects may be more likely or more severe depending on whether you're taking Zoloft® or Prozac®.

That said, you might switch from Zoloft® to Prozac® because: 

  • The medication simply isn’t working for you. It may take several weeks or even a couple of months for your body to fully feel the effects of either medication, but even then, you still might not feel improvement after taking it. A 2015 study found that one-third of individuals with depression have treatment-resistant depression, or TRD, meaning their depression doesn’t necessarily improve with initial treatment.

  • The side effects are too severe. From weight gain to difficulty sleeping, even a low dose of medication can have side effects. If they’re too intense or making you feel worse, you might want to consider switching. 

As always, if your side effects persist or you have concerns, reach out to your healthcare provider.

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Not only are there specific side effects associated with each individual medication, but there are also potential side effects that come with switching from Zoloft® to Prozac®. 

One of the biggest side effects to be aware of is antidepressant withdrawal. This can happen to folks who decide to discontinue using their medication abruptly. In fact, roughly one in five people will experience withdrawal when they suddenly stop taking their antidepressants or change the dosage. 

Just as it takes time for your brain to gradually adjust to a new medication, it takes time to adjust to not taking it. If you suddenly stop taking Zoloft®, for example, it could result in discontinuation symptoms or even a relapse in your anxiety or depression. The same applies if you were to stop taking Prozac®. 

For both Zoloft and Prozac, withdrawal symptoms can include: 

  • Insomnia 

  • Anxiety 

  • Mood changes

  • Irritability

  • Sweating

  • Dizziness

  • Confusion

How severe the symptoms are and how long they last are dependent upon the person. The bottom line? Quitting your meds without a game plan is never a good idea.

Below, we’ll outline the steps you should take instead. 

If you’re considering switching medications, it’s important to do so responsibly and under the guidance of a healthcare provider.

Depending on the antidepressant, it can be safe to switch immediately (also called a “direct switch”) to a replacement. But when it comes to transitioning from Zoloft® to Prozac®, tapering is the recommended technique.

Tapering involves slowly reducing your dosage of Zoloft® until you stop taking it altogether. The process of tapering usually involves lowering your dosage every couple of days over the course of several weeks.

Tapering off your meds might last longer or be shorter based on what your provider recommends and your tolerability. Once the sertraline is no longer in your system, your provider will likely have you start taking Prozac® at a dosage that works for your unique needs.

Cross-tapering is another technique where you gradually decrease the dosage of your current medication while simultaneously increasing the dosage of your new medication. 

Switching antidepressants isn’t as complicated as it may seem. Still, it’s crucial to listen to your healthcare provider to lower your chances of experiencing discontinuation syndrome and other negative side effects. 

If you’re curious about switching from Prozac® to a new medication — like escitalopram (Lexapro®), paroxetine (Paxil®), citalopram (Celexa® or Cipramil®)

or fluvoxamine (Luvox® or Faverin®) — our guide to antidepressant options can help you figure out which one is best for your needs.

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Thinking about swapping out your current medication for a new antidepressant is a big decision — but you don’t have to do it alone. With the help of your healthcare provider — be it a primary care provider or a psychiatrist — you can come up with the best plan for your specific needs and mental health.

In the meantime, there are plenty of other ways to build up your mental health in addition to medication. This can include: 

  • Opening up to a loved one. Talking about your struggles with a loved one not only normalizes them but also lets others know you need support — and there’s nothing wrong with that. The people who care about you the most want to show up for you in the best way possible, and letting them in — even if it’s a little scary — is the first step.

  • Therapy. Therapy is one of the most effective strategies for dealing with depression and anxiety. From cognitive behavioral therapy (CBT) to psychotherapy (or talk therapy), there’s a wide range of options to explore. If you don’t feel like meeting with someone in-person, online therapy is a super convenient alternative for connecting with a mental health professional.

  • Practicing self-care. Self-care looks different to everyone, but it’s ultimately about prioritizing your needs, which includes your mental health. For some, self-care means getting enough rest, breaking a sweat at the gym or taking time to journal in the morning. For others, it’s scheduling post-work margaritas with friends. The best part? It’s up to you.

Still feeling stuck? Our mental health services are always available with resources to point you in the right direction.

11 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.

  1. Major Depression. (n.d.-e). National Institute of Mental Health (NIMH). Available from: https://www.nimh.nih.gov/health/statistics/major-depression
  2. Singh, H. K. (2023c, February 13). Sertraline. StatPearls - NCBI Bookshelf. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547689/
  3. PROZAC. (2017, January). U.S. Food And Drug Administration. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018936s108lbl.pdf
  4. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554406/
  5. ZOLOFT. (2016, December). U.S. Food And Drug Administration. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019839s091lbl.pdf
  6. Ionescu, D. F., Rosenbaum, J. F., & Alpert, J. E. (2015). Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience, 17(2), 111–126. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518696/
  7. Gabriel, M., & Sharma, V. (2017). Antidepressant discontinuation syndrome. Canadian Medical Association Journal, 189(21), E747. Available from: https://www.cmaj.ca/content/189/21/E747
  8. Bhat, V., & Kennedy, S. H. (2017). Recognition and management of antidepressant discontinuation syndrome. Journal of Psychiatry & Neuroscience, 42(4), E7–E8. Available from: https://www.jpn.ca/content/42/4/E7
  9. Soreide, K. K., PharmD, K. M. W., & Bcpp, J. R. B. P. B. (2020, November 16). Strategies and Solutions for Switching Antidepressant Medications. Psychiatric Times. Available from: https://www.psychiatrictimes.com/view/strategies-and-solutions-switching-antidepressant-medications
  10. Keks, N. A., Hope, J., & Keogh, S. (2016). Switching and stopping antidepressants. Australian Prescriber, 39(3). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919171/
  11. Zwiebel, S., & Viguera, A. C. (2022). Discontinuing antidepressants: Pearls and pitfalls. Cleveland Clinic Journal of Medicine, 89(1), 18–26. Available from: https://www.ccjm.org/content/89/1/18

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 .

Education

  • 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

Publications

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