Zoloft® vs. Lexapro®: differences, side effects & which to choose

Zoloft® and Lexapro® are typically prescribed for many of the same reasons, and they’re similar enough that some wonder why their doctor chose one over the other. If you’re weighing the two, you’re probably asking which is more likely to help you.

Yet, there isn’t a one-size-fits-all answer. Zoloft and Lexapro are both Selective Serotonin Reuptake Inhibitors (SSRIs). However, they differ in FDA-approved uses, dosing, typical side effects, and how some people respond to them.

What are Zoloft and Lexapro?

Zoloft (sertraline) and Lexapro (escitalopram) are prescription antidepressants. Both are SSRIs, which work on serotonin. Serotonin is a brain chemical that affects depression, anxiety, sleep, memory, and sex drive. 

Your doctor may prescribe either medication for depression, anxiety, or both. However, they’re not the same, and it’s precisely those differences that make a difference in your treatment, including:

• How much your symptoms improve
• How quickly you notice a change
• Which side effects show up
• How easily you tolerate the medication

When it’s time to have a conversation about choosing the right antidepressant for your needs, your doctor will usually look at:

• Your main symptoms
• Side effects you’re worried about
• Other medications you take
• Your health history
• Whether you’ve tried antidepressants before

If the one you start with doesn’t help enough or the side effects are too much, your doctor can adjust the dose or talk with you about switching.

Zoloft vs. Lexapro quick comparison

Here’s a quick side-by-side look.

	Zoloft	Lexapro
Generic name	Sertraline	Escitalopram
What it treats	Adults: Major depressive disorder (MDD), panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD). Children ages 6–17: Obsessive-compulsive disorder (OCD).	Adults and children ages 12 and older: Major depressive disorder (MDD).  Adults and children ages 7 and older: Generalized anxiety disorder (GAD).
Available forms and strengths	Tablet: 25 mg, 50 mg, 100 mg Capsule (generic): 150 mg, 200 mgSolution: 20 mg/mL	Tablet: 5 mg, 10 mg, 20 mg Solution: 1 mg/mL
How it’s taken	Once daily, with or without food.	Once daily, with or without food.
Recommended storage	Store at room temperature, 68°F to 77°F. Keep the bottle tightly closed, away from moisture and direct light.	Store at room temperature, 68°F to 77°F. Keep the bottle tightly closed, away from moisture and direct light.
Typical treatment duration	Usually several months until symptoms ease. Most people keep taking it another 6 to 12 months to lower the chance of relapse.	Usually several months until symptoms ease. Most people keep taking it another 6 to 12 months to lower the chance of relapse.
Is there a risk of discontinuation symptoms?	Yes. Don’t stop suddenly on your own. Your provider will help taper you off.	Yes. Don’t stop suddenly on your own. Your provider will help taper you off.

At QuickMD, we treat adults for depression and anxiety, as well as sleep-related issues as a result of depression or anxiety. We do not treat obsessive-compulsive disorder (OCD) or post-traumatic stress disorder (PTSD)in our clinic.

What conditions do Zoloft and Lexapro treat?

Zoloft and Lexapro both treat depression and anxiety, but Zoloft has a broader range of FDA-approved uses. Providers may also prescribe either one off-label for a condition it isn’t FDA-approved to treat.

	Zoloft	Lexapro
Major depressive disorder (MDD)	FDA-approved	FDA-approved
Generalized anxiety disorder (GAD)	Off-label	FDA-approved
Obsessive-compulsive disorder (OCD)	FDA-approved	Off-label
Panic disorder	FDA-approved	Off-label
Post-traumatic stress disorder (PTSD)	FDA-approved	Off-label
Premenstrual dysphoric disorder (PMDD)	FDA-approved	Off-label
Social anxiety disorder (SAD)	FDA-approved	Off-label

How do Zoloft and Lexapro work?

Zoloft and Lexapro both raise the amount of serotonin available in your brain, which can ease depression and anxiety over time. Neither one works overnight, and most people wait several weeks to feel the full effect. 

Lexapro is a more targeted version of Celexa (citalopram), a related antidepressant. For most people, that means a lower effective dose, and sometimes fewer side effects. This combination of its targeted effect and lower dosage is why some people do better on Lexapro than on Celexa, though it’s not the better pick for everyone.

Zoloft works mainly on serotonin, too, but it also has a mild effect on dopamine, a brain chemical tied to motivation, focus, and energy. Sertraline has more of this dopamine activity than other SSRIs, which may be part of the reason why some people respond to Zoloft differently than to Lexapro.

Does Lexapro or Zoloft work better for depression and anxiety?

For most people, Lexapro and Zoloft work about equally well for depression and anxiety. The better choice depends on your diagnosis, symptoms, side effect concerns, other medications, and how you may have responded to antidepressants before. 

FDA approval reflects which conditions each medication has been tested and labeled for, not necessarily which one is better. A provider can prescribe either Lexapro or Zoloft off-label when the evidence supports it.

• For depression: Both Lexapro and Zoloft are FDA-approved for major depressive disorder. Studies show both are effective for long-term treatment, but the difference isn’t strong enough to say one works better for most people.
• For generalized anxiety disorder (GAD): Lexapro is FDA-approved for GAD and is a first-line treatment. Zoloft isn’t FDA-approved for it, but providers commonly prescribe it off-label when it fits a patient’s symptoms and history.
• For panic disorder and social anxiety: Zoloft is FDA-approved for both and is a first-line treatment. Lexapro isn’t FDA-approved here, but it’s a common off-label choice since it tends to be well tolerated.

Zoloft vs. Lexapro side effects

Just like with any other medication, it’s possible to experience side effects with Lexapro or Zoloft. However, seeing a side effect listed doesn’t mean it’ll happen. Rather, they’re just there to let you know what to watch for. 

Zoloft and Lexapro can cause similar side effects because they’re both SSRIs. Side effects can depend on your dose, how long you’ve been taking your prescription, other medications you use, and how your body responds. The side effects listed here are those that are reported most often. 

More common with both	More often associated with Zoloft	More often associated with Lexapro
Nausea, dry mouth, sleep changes, dizziness, sweating, sexual side effects	Diarrhea, tremor, decreased appetite	Fatigue, constipation

Most side effects are mild and ease up within the first week or two as your body adjusts. The sexual side effects are the exception, since those can last as long as you’re taking the medication, and you may want to bring them up with your doctor, since there are ways to manage them. Call your provider sooner if you notice unusual bruising or bleeding, or any worsening mood, especially in the first few weeks or after a dose change.

Get professional help with QuickMD

The right pick between Zoloft and Lexapro comes down to what you’re dealing with. Whether you’re experiencing anxiety, depression, or a panic disorder, having an honest conversation with a doctor about how you’re feeling day-to-day can help you both decide on a medication that can help. 

At QuickMD, you don’t have to go through it alone. You can start the conversation with a doctor from the comfort and privacy of home to get the answers and help you need. Your doctor will review your health history, current symptoms, and help you decide where to begin. If you’re already taking medication and it isn’t working, or a side effect is getting in the way, they can adjust your dose or switch you to something else.