Lexapro vs Zoloft: Key Differences and Similarities Explained

Expert Author
JORDYN L MASTRODOMENICO Counselor/Therapist Fair Lawn, NJ

Jordyn Mastrodomenico is a counselor in New Jersey. She evaluates patients using many different procedures, in order to determine what treatments must be carried out in order to properly assess their symptoms. Counselors provide consultation for each patient and their families.

When it comes to treating depression and anxiety disorders, Lexapro (escitalopram) and Zoloft (sertraline) are two of the most commonly prescribed antidepressants. Both belong to a class of medications called Selective Serotonin Reuptake Inhibitors (SSRIs), which work by increasing serotonin levels in the brain to improve mood. While they share many similarities, they also have distinct characteristics that may make one a better choice over the other depending on individual needs.

In this article, we’ll explore the key differences and similarities between lexapro vs zoloft, helping you make a more informed decision if you’re considering—or have been prescribed—either medication.

Choosing the Right ADHD Medication for You

When exploring treatment options for ADHD, it’s important to understand the differences between stimulant and non-stimulant medications. Two commonly prescribed options are strattera vs adderall, each working differently in the brain. While Adderall is a stimulant that increases dopamine and norepinephrine levels quickly, Strattera is a non-stimulant that gradually boosts norepinephrine activity. Choosing between Strattera vs Adderall often depends on individual health profiles, response to treatment, and potential side effects. Consulting a healthcare provider can help determine which medication better aligns with your needs, especially if there are concerns about substance misuse or stimulant-related side effects.

What Are Lexapro and Zoloft Used For?

Both Lexapro and Zoloft are primarily prescribed for major depressive disorder (MDD) and generalized anxiety disorder (GAD). However, their FDA-approved uses vary slightly:

As you can see, Zoloft has broader FDA-approved applications, particularly for anxiety-related conditions and OCD.

Mechanism of Action

Both medications work similarly by inhibiting the reabsorption (reuptake) of serotonin in the brain, making more of this mood-regulating neurotransmitter available to improve emotional state.

However, Lexapro is considered one of the more selective SSRIs, meaning it has a narrower focus and fewer interactions with other neurotransmitter systems. Zoloft, while also an SSRI, has mild effects on dopamine and sigma-1 receptors, which may explain why it’s effective for conditions like OCD and PTSD.

Effectiveness: Is One Better Than the Other?

Several studies and clinical experiences suggest both Lexapro and Zoloft are equally effective in treating depression and anxiety. However, individual response can vary.

  • Lexapro may work better for people with generalized anxiety disorder or pure depression, due to its clean pharmacological profile.
  • Zoloft might be more effective for patients with comorbid conditions such as OCD or panic disorder, thanks to its broader action spectrum.

Ultimately, personal response, side effect tolerance, and medical history will determine which drug is more effective for an individual.

Side Effects: What to Expect

Both medications come with a list of potential side effects. However, their profiles differ slightly:

Common Side Effects of Lexapro:
Common Side Effects of Zoloft:

Zoloft is more likely to cause gastrointestinal issues such as diarrhea, while Lexapro tends to be better tolerated in this regard. However, Lexapro may have a slightly higher chance of causing sedation or weight gain in some patients.

Dosage and Administration

Lexapro is usually prescribed in lower doses compared to Zoloft:

  • Lexapro: 10–20 mg once daily
  • Zoloft: 50–200 mg once daily

Despite the difference in milligrams, this does not indicate Zoloft is "stronger." These are just therapeutic dose ranges based on how the drugs metabolize in the body.

Both drugs are typically taken once a day, with or without food. Zoloft, however, may be taken in divided doses in some cases, particularly when treating OCD.

Withdrawal and Discontinuation

As with all SSRIs, both Lexapro and Zoloft can cause discontinuation symptoms if stopped abruptly, including dizziness, nausea, irritability, and flu-like symptoms.

Lexapro tends to have a shorter half-life, which means withdrawal symptoms may appear sooner after stopping. Tapering either medication slowly under medical supervision is always recommended.

Drug Interactions and Contraindications

Both medications can interact with:

  • MAO inhibitors (can cause serotonin syndrome)
  • NSAIDs or blood thinners (increased bleeding risk)
  • Other serotonergic drugs

Lexapro is metabolized primarily through CYP2C19, while Zoloft relies more on CYP2B6 and CYP2D6, meaning the risk and nature of interactions can differ based on other medications you are taking.

Always disclose your full medication list to your doctor before starting either drug.

Pregnancy and Breastfeeding

According to current research:

  • Lexapro is categorized as pregnancy category C.
  • Zoloft is also category C, but it is more frequently prescribed during pregnancy, especially for women with severe depression or anxiety.

Zoloft is generally preferred for breastfeeding mothers due to lower drug levels found in breast milk, but this should always be discussed with your doctor.

Cost and Availability

Lexapro and Zoloft are both available in generic forms (escitalopram and sertraline), making them relatively affordable. Most insurance plans cover both options.

In terms of cost:

  • Generic sertraline (Zoloft) is often slightly cheaper.
  • Escitalopram (Lexapro) may be more expensive in branded form but is competitively priced as a generic.

Final Thoughts: Which Should You Choose?

Choosing between Lexapro vs Zoloft depends on several factors:

  • Type of condition being treated
  • Personal response and side effect tolerance
  • Medical history and other medications
  • Lifestyle preferences (e.g., dosing time, side effects)

If your primary concern is generalized anxiety or mild to moderate depression, Lexapro might be the cleaner, simpler choice. However, if you're dealing with more complex or multiple conditions, such as OCD or PTSD, Zoloft may offer broader relief.

As always, the best choice is one made in partnership with your healthcare provider. Both medications have helped millions of people find balance—what matters most is how your body responds.