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Lexapro vs. Zoloft: Comparing medications

Lexapro vs. Zoloft: Comparing medications

Reviewed by:
Michael Roman, MD
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June 6, 2024
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Key takeaways

  • Lexapro and Zoloft are both SSRI antidepressants that increase serotonin.
  • They differ in approved conditions but are both generally effective for treating depression.
  • Both can cause side effects like sexual dysfunction, nausea, and sweating.
  • The choice between Lexapro or Zoloft, or another antidepressant, should be made in consultation with a doctor who can consider factors like the patient's specific symptoms, medical history, and other personal needs to determine the best treatment plan.
In this article

If you're struggling with depression or anxiety, know that medication helps. Two commonly prescribed medications are Zoloft and Lexapro. While Lexapro and Zoloft have many similarities—they belong to the same class of medication, and treat some of the same conditions like anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder—there are some key differences between them as well.  

In this article, we’ll compare both medications, including how they work, their side effects, and more.  

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What conditions do they treat?

Both Lexapro (escitalopram) and Zoloft (sertraline) differ in the conditions they are approved to treat and their off-label uses. Off-label means the FDA has not approved the medication to treat this condition—but doctors may prescribe it based on scientific evidence and clinical research.  

Before we get into how Zoloft and Lexapro can make you feel better, check out the chart below to see their different uses.

Condition Lexapro Zoloft
Major depressive disorder (MDD) Approved Approved
Generalized anxiety disorder (GAD) Approved Off-label
Social anxiety disorder Off-label Approved
OCD Off-label Approved
PTSD Off-label Approved
PMDD Off-label Off-label
Vasomotor symptoms of menopause Off-label Off-label
Binge eating disorder n/a Off-label
Bulimia nervosa n/a Off-label

How do they work?

Lexapro and Zoloft belong to a class of medications called SSRIs (selective serotonin reuptake inhibitors). SSRIs work by altering the amount of serotonin that is available in your brain. Serotonin is a chemical messenger or neurotransmitter involved in many of the body’s most important processes, helping to regulate everything from mood, memory, and perception of pain, to sleep and your gastrointestinal system.  

According to research, low serotonin levels can contribute to many mental health conditions, like anxiety and depression. SSRIs like Lexapro and Zoloft make more serotonin available in your brain—which in turn helps to relieve symptoms..  

Some research suggests that Lexapro might be slightly more effective than Zoloft in treating depression and anxiety because it works slightly differently from other SSRIs. Lexapro is the only SSRI that’s classified as an allosteric serotonin uptake inhibitor, which means it can result in higher levels of serotonin in the brain, than other SSRIs, like Zoloft.  

Keep in mind that this doesn’t necessarily mean that Lexapro is a better choice for you than Zoloft, or another SSRI. There are other considerations to make when selecting a medication—like side effects and interactions with medication. Treatment is highly personalized and your doctor will take several factors into account before recommending a treatment plan.

What are their side effects?

Like all medications, Lexapro and Zoloft come with a risk of side effects. Most of these are mind, and will go away as your body adjusts to medication. Before you’re prescribed a medication, your doctor will consider your health history, family history, and other factors to help minimize your risk of experiencing side effects..It can be helpful to  know which side effects to look out for as you’re starting a new medication. If you do  notice any side effects, be sure to tell your doctor. They may recommend adjusting your dose or switching to a new medication..  

Common side effects of Lexapro

  • Sexual dysfunction, such as decreased libido, erectile dysfunction, and delayed orgasms
  • Nausea
  • Dry mouth
  • Weight gain
  • Fatigue  
  • Excessive sweating

A rare adverse effect of Lexapro is QT prolongation, or an irregular heart rhythm.  

Common side effects of Zoloft

  • Nausea
  • Weight gain
  • Sexual dysfunction
  • Excessive sweating  
  • Dry mouth
  • Dizziness
  • Diarrhea
  • Fatigue

There’s a risk of increased suicidal thoughts for young adults and adolescents when taking either Lexapro or Zoloft.  

What are their common drug interactions?

Certain prescription drugs, over-the-counter medications, vitamins, or supplements can change the way Lexapro or Zoloft works in your body. This is referred to as a medication interaction. For instance, it can be especially risky to pair Lexapro and Zoloft with other drugs or supplements that increase serotonin because of the risks of serotonin syndrome.  

Serotonin syndrome is rare, and symptoms can include an elevated temperature, hypertension, dizziness, vomiting, diarrhea, and other problems. At its worst it can cause issues like seizures or a coma. Serotonin syndrome may sound scary, but it's very rare and your doctor will help you reduce your risk. If you have any concerns, be sure to bring them up to your doctor.

Lexapro’s drug interactions include:  

  • Monoamine oxidase inhibitors (MAOI) like linezolid or methylene blue
  • Non Steroidal Anti-inflammatory Drugs (NSAIDs) can increase risk of bleeding when taken with Lexapro
  • St. John’s Wort
  • SSRIs (especially Celexa, which is very similar) and serotonin–norepinephrine reuptake inhibitors (SNRIs)
  • Amiodarone, a medication for irregular heartbeat

Zoloft’s drug interactions include:  

  • Antipsychotics like pimozide and thioridazine
  • MAOIs  
  • St. John’s Wort
  • SSRIs and SNRIs
  • Certain anticoagulants
  • NSAIDs

Can you take them together?

Sometimes combining certain antidepressant medications can help lessen symptoms of depression. However, Lexapro and Zoloft shouldn’t be combined specifically because they can increase a person’s risk of developing serotonin syndrome as mentioned before. You also wouldn’t take Lexapro or Zoloft with another SSRI like Prozac (fluoxetine).

What to know before taking Lexapro or Zoloft

SSRIs like Lexapro and Zoloft aren't recommended for everyone and in some cases, your doctor may suggest another type of antidepressant instead. For example, Lexapro may not be the right choice for someone with bipolar disorder as it can increase the risk of mania, according to some research.  

Before prescribing you something, your doctor will ask about your health history, family history, current symptoms, and other medical conditions. This information will help them make decisions about your treatment.

Pregnancy and breastfeeding

If you’re pregnant or breastfeeding you should let your doctor know. Zoloft can also be taken during pregnancy, and healthcare providers typically prefer prescribing this antidepressant over others to women who are breastfeeding. While Lexapro can be taken during pregnancy, there can be risks. If you’re breastfeeding, your doctor will likely recommend a lower dose due to the slight risk of necrotizing enterocolitis (NEC), dangerous intestinal inflammation that only appears in babies.  If you have more questions, you can also talk to your OB/GYN.

Kidney issues

People with poor kidney function can usually take Lexapro or Zoloft without any major concerns. However, if someone has serious renal impairment, your doctor may prescribe a lower dosage of either medication based on the level of renal impairment.  

Older adults

Before prescribing an antidepressant, your doctor will also take your age into account, as this can impact the effectiveness of a medication. Both Lexapro and Zoloft can have different implications for people over the age of 65. There’s the risk that they can cause your body to retain too much water, causing hyponatremia, an extreme electrolyte imbalance. This can cause nausea, a headache and other severe problems like seizures.  

Is Lexapro or Zoloft better?

Lexapro and Zoloft have a few key similarities and differences. Both are SSRIs, which means they function similarly within the brain to treat a variety of mental health conditions. They also have many similar side effects and interactions.  Ultimately, if you’re struggling with mental health symptoms , a doctor can help you find the best treatment option for you based on your personal needs.

Lexapro, which has been approved to treat major depressive disorder and general anxiety disorder, might be more effective at boosting serotonin than Zoloft, according to research. Yet, Zoloft has been approved by the FDA to treat more conditions, like OCD, PTSD, panic attacks, and social anxiety.  

If you are looking for mental health treatment, and don’t know where to start, you’re in the right place. Talkiatry is a national psychiatry practice that provides in-network care. Take our quick assessment and get matched with a psychiatrist today.


What are the similarities between Zoloft and Lexapro?

Both Zoloft and Lexapro are SSRIs that have been FDA-approved to treat major depressive disorder.  

Does Lexapro or Zoloft cause more weight gain?

Research has shown that Lexapro might cause more weight gain than Zoloft. However, the difference is minimal and everyone responds to medication differently. To learn more about antidepressants and weight gain, check out: Do antidepressants cause weigh tloss?

What are other antidepressants medications?

Other SSRIs include Paxil (paroxetine) and Celexa (citalopram). Other types of antidepressants include SNRIs (serotonin and norepinephrine reuptake inhibitors) like Cymbalta (duloxetine), MAOis (monoamine oxidase inhibitors), TCAs (tricyclic Antidepressants), and atypical antidepressants like Wellbutrin (bupropion).  

The information in this article is for education and informational purposes only and should never be substituted for medical advice, diagnoses, or treatment. If you or someone you know may be in danger, call 911 or the National Suicide and Crisis Lifeline at 988 right away.

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What's the difference between a therapist and psychiatrist?

Psychiatrists are doctors who have specialized training in diagnosing and treating complex mental health conditions through medication management. If you are experiencing symptoms of a mental health condition such as depression, anxiety, bipolar disorder, PTSD, or similar, a psychiatrist may be a good place to start.  

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  • Your primary care doctor or another doctor thinks you may benefit from the services of a psychiatrist and provides a referral    
  • You are interested in taking medication to treat a mental health condition  
  • Your symptoms are severe enough to regularly interfere with your everyday life

The term “therapist” can apply to a range of professionals including social workers, mental health counselors, psychologists, professional counselors, marriage and family therapists, and psychoanalysts. Working with a therapist generally involves regular talk therapy sessions where you discuss your feelings, problem-solving strategies, and coping mechanisms to help with your condition.

Who can prescribe medication?

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Michael Roman, MD

Dr. Michael Roman is currently a Staff Psychiatrist at Talkiatry. He completed his adult psychiatry residency training at the University of Pennsylvania. Dr. Roman is a board-certified Adult Psychiatrist and a diplomate of the American Board of Psychiatry and Neurology (ABPN).

Dr. Roman’s clinical practice centers primarily around medication management and psychopharmacological treatment approaches. He also specializes in a variety of psychotherapeutic modalities which he utilizes in conjunction with medication management in order to provide patients with the best possible treatment outcomes.

Dr. Roman’s curiosity for the studies of the human mind began with pursuing a bachelor’s degree in psychobiology at the University of California, Los Angeles (UCLA). He was intrigued by the way our mind, body, emotions, and behavior were intertwined to comprise our everyday life experiences. His interest in the intricacy of the human mind was deepened in medical school, and he received his medical degree from the David Geffen School of Medicine at UCLA. He completed his adult psychiatry residency training at the University of Pennsylvania.

Dr. Roman treats a wide spectrum of patients, but his primary clinical focus is treating mood disorders, ADHD, anxiety disorders, and PTSD. Dr. Roman also specializes in treating substance use disorders and possesses clinical expertise in implementing high quality motivational interviewing and motivational enhancing therapy.

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