Switching from Zoloft to Prozac: What to Expect

If you’re prescribed antidepressants, you might need to try different ones or adjust doses before you find the right fit. Switching from Zoloft® to Prozac®, for example, is common and manageable, but it can be confusing. When is the right time to make the big switch? What are the risks? How do you go about doing it safely?

Before making any changes, you should always consult with your healthcare provider for medical advice. In the meantime, we’ll run through these questions and offer insight into how to switch antidepressants safely, so you’re equipped with preliminary info as you navigate the process.

Let’s start with the basics: Zoloft and Prozac belong to a category of antidepressants called SSRIs, or selective serotonin reuptake inhibitors. They work by targeting a neurotransmitter called serotonin, also known as the “happy hormone,” as it plays a role in regulating mood.

Because of their effectiveness, both Zoloft® and Prozac® are considered first-line treatments for depression, as well as certain anxiety disorders.

Zoloft (the brand name for sertraline) was approved by the FDA in 1991. It can treat:

• Major depressive disorder (MDD)

• Obsessive-compulsive disorder (OCD)

• Panic disorder

• Post-traumatic stress disorder (PTSD)

• Social anxiety disorder

• Premenstrual dysphoric disorder (PMDD)

Prozac (the brand name for fluoxetine) was approved by the FDA in 1987. It can treat:

• MDD

• OCD

• Bulimia nervosa

• Panic disorder

Both Prozac and Zoloft come in a few different forms: liquid oral solution, tablets, and capsules.

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 some overlapping common side effects, such as: 

• Nausea (22% of Prozac-treated patients and 26% of Zoloft-treated patients)

• Insomnia (19% of Prozac-treated patients and 20% of Zoloft-treated patients)

• Diarrhea (11% of Prozac-treated patients and 20% of Zoloft-treated patients)

• Fatigue and sleepiness (12% in both)

Other common overlapping side effects include:

• Dyspepsia, or indigestion

• Tremors

• Sweating

• Decreased libido

• Abnormal ejaculation and erectile dysfunction

• Serotonin syndrome

Both antidepressant medications could cause several other potential side effects, but some of these side effects may be more likely or more severe depending on whether you're taking Zoloft vs. Prozac.

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

• The medication simply isn’t working for you. It may take a few 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. One 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. Even though both medications have a similar effect on your brain, for reasons that aren’t understood, you may have much more success with one over the other.

• The side effects are too severe. From appetite changes leading to weight gain or weight loss to difficulty sleeping, even a low dose of medication can have side effects. If the side effects are too intense or are making you feel worse, you might want to consider switching to a new antidepressant. As with effectiveness, even though they have very similar side effect profiles on average, an individual might have a very different experience on one compared to the other. We don’t know why.

• You have a condition that one medication doesn’t treat effectively. Certain disorders aren’t on the approved indications list for Prozac, or generic fluoxetine. If you have a form of anxiety or depression that’s better treated by another medication, your prescriber may suggest you switch from Prozac or Zoloft.

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

Not only are there specific side effects associated with each medication, but there are also potential side effects that can 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 adjust to a new medication gradually, 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

The severity and duration of these symptoms vary from person to person. 

The bottom line? Quitting your meds without a game plan — and medical advice — isn’t 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 you’re taking and how long you’ve been on it, it might 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. It usually involves lowering your dosage every 4-7 days over the course of several weeks. That said, tapering off your meds might take more time or less, depending on your dosage, the amount of time you’ve been taking the medication, and your individual sensitivity to the taper.

Once the sertraline is no longer in your system (also known as the “washout period”), 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. The advantage of cross tapering is that switching takes less time and you’re never off an antidepressant completely, which can lead to a return of your symptoms. The disadvantage is that taking two SSRIs at the same time can magnify the side effects.

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

Alternatives to Zoloft and Prozac

In addition to Zoloft and Prozac, several other types of medications are also used to treat depression, anxiety, and other mental health conditions. These include:

• Other selective serotonin reuptake inhibitors (SSRIs). Examples include citalopram (Celexa®), paroxetine (Paxil®), escitalopram (Lexapro®), and fluvoxamine (Luvox®). Like Zoloft and Prozac, they also work by modifying serotonin activity in the brain.

• Serotonin-norepinephrine reuptake inhibitors (SNRIs). This class of antidepressants works by targeting serotonin and norepinephrine activity. Norepinephrine is another neurotransmitter that plays a role in mood regulation. Examples include desvenlafaxine (Pristiq®), duloxetine (Cymbalta®), and venlafaxine (Effexor®).

• Other antidepressants. Your healthcare provider may prescribe another antidepressant, such as bupropion (Wellbutrin®), which is considered an “atypical antidepressant” because it doesn’t neatly fit within another category. Bupropion acts on dopamine and norepinephrine, two other hormones and neurotransmitters that also play a role in mood.

• Tricyclic antidepressants (TCAs). TCAs are an older class of antidepressants (one example is nortriptyline, the active ingredient in Pamelor® ). They aren’t typically prescribed as first-line treatments for depression. However, a healthcare professional may prescribe a tricyclic antidepressant if your depression has failed to respond to treatment with other medications.

• Monoamine oxidase inhibitors (MAOIs). These older antidepressants are also rarely used due to their risk of side effects and drug interactions. However, your healthcare provider may prescribe a MAOI if newer antidepressants are unsuccessful for you.

If you’re curious about switching from Zoloft or Prozac to a new medication, our guide to antidepressant options can help you figure out which one is best for your needs.

In addition to medication, there are also other steps you can take in the meantime to build up your mental health. This can include:

• Opening up to a loved one. Talking about your struggles with a loved one 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.

• Talk therapy. Psychotherapy is one of the most effective strategies for dealing with depression and anxiety. From cognitive behavioral therapy (CBT) to psychodynamic therapy, there are 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 for everyone, but it’s ultimately about prioritizing your needs, which includes your mental health. For some, self-care means getting enough sleep, breaking a sweat at the gym, or taking time to journal in the morning. For others, it’s scheduling a post-work hang with friends. The best part? It’s up to you.

Thinking about swapping out your current depression or anxiety medication for a new one is a big decision, and 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.

Here’s what to keep in mind when it comes to switching from Zoloft to Prozac:

• Zoloft and Prozac are both effective treatments for a variety of mental health conditions. They’re also both SSRIs, which act on serotonin.

• They have different active ingredients and are approved to treat different conditions. Prozac (fluoxetine) is FDA-approved to treat major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), and bulimia, while Zoloft (sertraline) is approved to treat MDD, OCD, PD, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder.

• It’s normal to switch antidepressants. If either Zoloft or Prozac isn’t working for you, or if you have side effects that don’t seem to improve over time, your healthcare provider may suggest making a switch to another medication. 

• Follow medical advice to switch medications safely. Make sure you work with a healthcare provider during this transition, and let them know if you experience any side effects or withdrawal symptoms.

Ready to take the next step? We offer access to psychiatry services and are always available to help you get started on your mental health journey.