Celexa vs Zoloft: How they compare, what they treat, and how to choose

Celexa vs Zoloft: A quick overview

Celexa (citalopram) and Zoloft (sertraline) are both selective serotonin reuptake inhibitors (SSRIs). They work by preventing serotonin from being reabsorbed too quickly in the brain, which helps regulate mood. Both are FDA-approved for major depressive disorder. Zoloft is also approved for some types of anxiety, whereas anxiety is an off-label use for Celexa.

Both medications are about equally effective for depression, so the choice often comes down to which conditions you’re treating, how you respond to the medication, potential side effects, and drug interactions.

Celexa vs Zoloft: A side-by-side comparison

This table breaks down the main differences between Celexa and Zoloft to help you understand how each medication might fit your specific situation.

Conditions each medication may work better for

“When patients ask whether Celexa or Zoloft is ‘better,’ I explain that neither is necessarily better than the other,” says Kate Hanselman, PMHNP, vice president of clinical psychiatry at Thriveworks. “It really comes down to what works best for you and your body. When I recommend one medication over another, I explain that choice in terms of what we’re prioritizing, whether that’s mood symptoms, anxiety, tolerability, or safety considerations.”

Celexa and Zoloft are equally effective and first-choice options for MDD. But Zoloft has FDA approval for several anxiety-related conditions where Celexa doesn’t. This matters because FDA approval typically means more research supporting that use, which can give you and your provider more confidence in the treatment choice. Here’s a breakdown:

Keep in mind, therapy may be equally or more effective than either medication for some mental health conditions. For example, exposure and response prevention therapy (ERP) is the first-choice treatment for OCD. Dialectical behavior therapy (DBT) is the first-choice treatment for borderline personality disorder (BPD).

There may also be times when your provider recommends combining therapy with medication to improve your chances of success.

Practical considerations when choosing between Celexa and Zoloft

Beyond FDA approvals and side effects, here are four practical factors that might influence which medication works better for you.

1. How quickly they may start working: Both medications take time. Some people notice small early changes within a few weeks. But it often takes six to eight weeks to feel the full effect.
2. Dosing flexibility: Celexa comes in 10 mg, 20 mg, and 40 mg tablets, plus 30 mg capsules. Zoloft comes in 25 mg, 50 mg, and 100 mg tablets, plus 150 mg and 200 mg capsules. Both come in strengths that allow you to gradually increase the dosage. The maximum recommended dosage for Celexa is 40 mg, while the maximum recommended dosage for Zoloft is 200 mg. So Zoloft may provide more flexibility to adjust dosages up or down based on how you respond to the medication.
3. Sensitivity to side effects: While everyone responds differently, all SSRIs can cause nausea, weight changes, sleep changes, headache, and diarrhea. Zoloft may be more likely to cause diarrhea than Celexa, especially in the beginning as your body adjusts to the medication.
4. Other medications or health conditions: Celexa is more likely than Zoloft to cause a heart condition called long QT syndrome. If you’re at an increased risk of long QT syndrome, Celexa may not be the best choice. Zoloft affects certain liver enzymes (called CYP enzymes) that help your body process medications. This means Zoloft has more potential drug interactions than Celexa. Your provider or pharmacist will review your medication list to check for interactions before you start on either medication.

What to expect during the first few weeks on either medication

Starting Celexa or Zoloft comes with an adjustment period, and progress happens gradually, not all at once.

Week 1–2: Early side effects and first signs of improvement

During the first few days to weeks, you may notice side effects like nausea, headache, diarrhea, or feeling slightly more restless. “These symptoms are common early on and don’t necessarily mean the medication isn’t right for you,” Hanselman says. “It can also take several weeks to see the full benefit of an SSRI, so patience is important.”

Most of these side effects improve as your body adjusts to the medication. Both medications can also cause weight changes.

Some people also begin feeling early effects from the medication within the first week or two—perhaps slightly better sleep, improved energy, or less emotional heaviness. This doesn’t mean you’re at full therapeutic benefit yet, but it’s a sign the medication is starting to work.

RELATED: Does Zoloft cause weight gain? Here’s what the research shows

Week 6–12: Full benefits emerge

It typically takes six to eight weeks to feel the full effect of either medication. Some people need up to 12 weeks. This is why sticking with the medication is important, even if you don’t feel dramatically better at first.

What your provider will monitor

You may see your provider more often during the first few months. They’ll ask about how you’re feeling and what side effects you’re experiencing to understand how you’re responding. They may also adjust your dosage until they find the right amount for you.

When to reach out: Contact your provider if side effects feel severe or suddenly worsen. If you’re having thoughts of harming yourself, seek medical attention or call the 988 Suicide & Crisis Lifeline immediately.

How to switch between Celexa and Zoloft

Switching between Celexa and Zoloft should always be done with guidance from your healthcare provider. Even though both medications work in similar ways, stopping one suddenly or changing doses too quickly can lead to uncomfortable side effects, including antidepressant discontinuation syndrome.

Your provider will help you gradually get off of one medication while simultaneously getting on the new medication. That will help reduce the chance of side effects during the switch.

Talking with a provider can help you make the right choice

Choosing between Celexa and Zoloft is usually less about finding the “best” medication and more about finding the right fit for you. Your healthcare provider can help weigh your symptoms, side effects, medical history, and personal goals to recommend a medication that may be best for you.

“The most important thing I want patients to know is that we’re making the choice based on your needs and your overall health and wellness,” Hanselman says. “It’s not about picking the ‘right’ antidepressant on paper. It’s about choosing the option that best fits your needs.”

It’s important to bring a complete list of your medications to your appointment, including any OTC or herbal medications you take. It’s also a good idea to be sure your provider has a list of all of your medical conditions, even if you see another clinician for it.

During your appointment, they may ask questions like:

• Have you taken antidepressants before, and how did you respond to them?
• What symptoms are most important to you right now? Low mood, anxiety, panic, sleep changes, or something else?
• Are there side effects you’re especially concerned about, or want to avoid?

The bottom line

Zoloft and Celexa are SSRIs and first-choice medications for depression. Zoloft is also FDA-approved for some types of anxiety. Both medications can cause headache, nausea, changes in sleep, and changes in weight. Zoloft is more likely to cause diarrhea, while Celexa is more likely to cause long QT syndrome.

The right medication for you will depend on what it is being used for, your other medications and medical conditions, and potential side effects and drug interactions. Thriveworks can connect you with a licensed clinician who can help find the right treatment option for you.

Frequently asked questions

Is Celexa or Zoloft better for anxiety?

Zoloft may be more effective for anxiety, but Celexa can still help some people. Zoloft has more research and FDA approval for several anxiety-related conditions. Celexa is commonly used off-label for anxiety and works well for some people. The best choice often depends on how anxiety shows up for you and how you’ve responded to medications in the past.

Which medication has fewer side effects?

Both medications have side effects, but they are a little different. Celexa and Zoloft share many common SSRI side effects, including headache, changes in weight, and changes in sleep. Zoloft is more likely to cause stomach-related side effects like diarrhea. Celexa is more likely to cause a heart condition long QT syndrome.

How long does it take for each to work?

Both medications take time and work at a similar pace. Some people notice some improvement within the first week or two. But it usually takes at least eight weeks, and up to 12 weeks, to get the full benefit of either medication. Neither Celexa nor Zoloft has been shown to work faster than the other in a consistent way. The goal is steady progress, rather than immediate results.

Are Celexa and Zoloft equally effective for depression?

Yes, they are about equally effective for depression. Large studies show that Celexa and Zoloft work about equally as well for depression. Because neither one really outperforms the other, the right choice often depends on side effects, medical history, and other medications. Finding the right fit matters more than the specific medication name.