Lexapro vs Zoloft: Key Differences Between Popular SSRIs

What Are SSRIs – And How Do They Work?

SSRIs are a class of antidepressant medications.

SSRIs work by increasing the amount of serotonin that the human brain has to work with. Serotonin is often referred to as the “happiness hormone,” and that’s a good working description. More technically, it’s a neurotransmitter that helps regulate mood, sleep, and stress.

Normally, after serotonin is released between brain cells, it’s reabsorbed (“reuptaken”) by the cell that released it.

SSRIs slow down this reuptake process, allowing serotonin to stay active in the brain for longer. That’s how they get their name: Selective serotonin reuptake inhibitors.

By selectively inhibiting reuptake of serotonin, they increase exposure to serotonin – and facilitate better sleep, lower stress, and a more regulated mood.

Though all SSRIs, Lexapro and Zoloft included, share this general mechanism, each has a slightly different chemical profile.

Their inherent differences can affect how quickly they work, how they interact with other receptors, and how people tolerate them.

Here’s a little more detail about each:

Lexapro vs Zoloft: Which Is Prescribed for What?

After you talk to your doctor about your symptoms, they’ll help you determine which might be a good medication to start taking.

One of the main criteria guiding that decision is, simply, what each medication is officially used to treat.

(You may be able to take one of these medications “off label,” or for something outside of its official purpose, but starting with approved use is likely a good idea.)

What Are the Approved Uses of Zoloft and Lexapro?

Both Lexapro and Zoloft treat major depressive disorder (MDD) and various forms of anxiety.

That said, the list of conditions that Zoloft is approved to treat is a little longer than Zoloft’s.

Lexapro is approved for:

Zoloft, on the other hand, is approved for:

Practically speaking, what this means is Zoloft tends to be recommended for patients whose anxiety symptoms are more specific or severe, such as panic attacks or intrusive thoughts.

Lexapro may be ideal for those who experience generalized or situational anxiety alongside depression.

However, these are just general guidelines.

What works best for you is something that you (and your doctor!) get to decide.

Here’s Exactly How Lexapro and Zoloft Work in the Body

Both Lexapro and Zoloft increase the available serotonin levels that the human brain has access to.

However, the ways in which each of these medications accomplishes this goal give them subtle but meaningful differences in how they feel to patients.

Lexapro: Smooth and Focused Serotonin Regulation

Lexapro is considered one of the cleanest SSRIs.

As we mentioned above, this is because it does a very good job of targeting just the serotonin transporter without affecting other activity.

This selectivity may contribute to its low incidence of side effects and smoother overall experience, especially for people sensitive to stimulation or sedation.

Because of this, many prescribers start new patients on Lexapro when they’re seeking a gentle first-line antidepressant.

It’s often praised for its balanced, calming effect, particularly in people with generalized anxiety disorder or mixed anxiety and depression.

Lexapro also has a relatively long half-life (about 27 to 32 hours).

A half-life is a measure of how long it takes for a substance to degrade. Having a longer half-life means that the substance – Lexapro – lasts longer in the body.

This means it can be easier to maintain consistent blood levels of the medication in your blood, and, therefore, can sometimes make dose adjustments or discontinuation easier than with shorter-acting SSRIs.

Zoloft: Broader Activity and Energizing Potential

Zoloft also inhibits serotonin reuptake quite well.

But it’s not quite as selective as Lexapro. At higher doses, it mildly affects dopamine and norepinephrine reuptake as well.

That broader activity can make it feel slightly more energizing or activating than Lexapro for some users. This can be a benefit for people with depression-related fatigue, low motivation, or social anxiety.

However, that same activation may trigger other side effects during the first week or two of treatment, such as mild jitteriness, restlessness, or gastrointestinal upset.

For most patients, these symptoms subside as the body adjusts.

Zoloft’s half-life is roughly 24 hours, which supports once-daily dosing but can result in a slightly more noticeable “wear-off” if a dose is missed compared to Lexapro.

Side Effects: Lexapro vs Zoloft

Every SSRI has potential side effects, and while Lexapro and Zoloft are both considered highly tolerable, each carries its own profile of possible risks.

Knowing ahead of time what you can expect should make it easier to stick with your treatment if doing so is your goal.

Common side effects of Lexapro include:

Common side effects of Zoloft include:

For both Lexapro and Zoloft, these side effects should be both mild and temporary.

If these symptoms persist and have a negative impact on your life, or if you think you can link any other undesired side effects to your new medication use, your provider may lower your dose or suggest switching to another SSRI.

Weight Gain: Zoloft vs Lexapro

Both Lexapro and Zoloft can cause modest increases in weight for some users.

This can be a concern for people when they start taking antidepressants.

And it’s understandable.

Fortunately, we have good news.

Any weight gain you do see after beginning Zoloft or Lexapro should be minimal, and weight gain associated with these drugs tends to vary widely on an individual basis.

If you’re worried about gaining weight but you’re still interested in benefiting from one of these SSRIs, you can always:

Lexapro vs Zoloft in Older Adults

For seniors, both Lexapro and Zoloft are among the safest antidepressants available.

They have low risks of drug interactions compared to older antidepressants and are less likely to cause sedation or blood pressure changes.

Doctors often choose between them for their patients based on patient drug tolerance and comorbidities, or the other health challenges that a patient may be working through.

Let’s take a quick look at these medications through that lens:

Because older adults metabolize drugs more slowly, a doctor might recommend smaller initial doses (e.g., Lexapro 5mg daily or Zoloft 25mg daily to start).

What About ADHD or Other Off-Label Uses?

Neither Zoloft nor Lexapro is officially approved for ADHD.

That said, sometimes doctors may decide to prescribe either medication off-label to treat any emotional dysregulation or anxiety that can accompany attention disorders.

Zoloft may be more energizing and helpful when focus and motivation are affected.

Lexapro may be preferable when anxiety or mood instability are the main concerns.

In these cases, SSRIs are usually combined with therapy or stimulant medications. This should only be done under careful supervision.

Dosing and Practical Use: Lexapro 10mg vs Zoloft 50mg

Lexapro and Zoloft differ in potency, or concentration/strength.

This means that a starting dose of Lexapro will seem much smaller than Zoloft’s, but the standard starting dose of each is roughly equivalent in the type of effect it will produce.

Regardless of which you take, you’ll likely follow a similar dosing regimen.

You’ll take either Lexapro or Zoloft once daily, usually in the morning, to minimize sleep disruption. Neither requires food, though Zoloft may be easier on the stomach if taken after a meal.

What About Switching Between Lexapro and Zoloft?

If one SSRI isn’t working as hoped, your doctor may recommend switching.

This is a normal process, and not one to worry about.

But it is something to manage carefully, usually through something called a “cross-taper,” where one medication is slowly reduced while the new one is introduced.

Your specific switching protocol and the medication you’re discontinuing or starting will, of course, depend on your unique set of symptoms and health goals.

Your doctor will also help you make this decision.

But, generally speaking:

Never, ever stop or switch antidepressants suddenly without medical supervision. Doing so may cause withdrawal symptoms like dizziness, brain “zaps,” or irritability.

Cost and Availability: Generic Options from Trusted Pharmacies

Both Lexapro and Zoloft are available in generic forms, escitalopram and sertraline, respectively. These generic meds are among the most affordable antidepressants worldwide.

You can also, if you so choose, get them shipped directly to your front door.

Here, through NorthWestPharmacy.com, you can buy:

Here’s the good news: There’s no universal “winner” between Lexapro and Zoloft.

Both are excellent, well-researched medications with proven benefits.

The best choice depends on your specific needs:

Choose Lexapro if you:

Choose Zoloft if you:

While their subtle differences can matter, both medications share one goal: to help you restore balance and quality of life.

We’re here to help you achieve that goal, too.

As you and your doctor determine your next best steps, feel free to reach out to our team at any time for practical information about either of these or other mental health medications.

Then, when you’re ready to buy, our team is here to assist with that, too. The staff at NorthWestPharmacy.com looks forward to supporting you and your healthcare journey!