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Lexapro® and Zoloft® are two of the most common medications used to treat major depressive disorder (MDD).
If Lexapro isn’t working well for you or is causing too many side effects, your healthcare provider may suggest switching from Lexapro to Zoloft.
Switching antidepressants is a very normal thing. In fact, it’s common to try several medications before finding one that offers the right balance of improvements in your symptoms and tolerable side effects.
Below, we’ve explained what Lexapro and Zoloft are, as well as why your mental health provider may suggest switching from one medication to the other.
We’ve also discussed how you can safely switch from Lexapro to Zoloft without increasing your risk of developing withdrawal symptoms or experiencing a relapse of your depression.
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Lexapro is a popular, widely-used antidepressant. It contains the active ingredient escitalopram and belongs to a class of antidepressant drugs called selective serotonin reuptake inhibitors, or SSRIs.
Currently, Lexapro is approved by the Food and Drug Administration (FDA) to treat major depressive disorder and generalized anxiety disorder (GAD).
Like other SSRIs, Lexapro works by increasing the amount of serotonin that’s active throughout your brain and body.
Serotonin is a neurotransmitter — a type of molecule that’s used by your central nervous system to transmit messages between cells. Your brain uses serotonin to regulate many aspects of your moods, including feelings of happiness and anxiety.
Low levels of serotonin are associated with several mental disorders, including an increased risk of depression, anxiety and obsessive-compulsive disorder.
By increasing serotonin levels, Lexapro helps to reduce the severity of symptoms of anxiety and depression, promoting stable moods and better mental balance.
Our full guide to escitalopram goes into more detail about how Lexapro works as a treatment for depression and anxiety disorders, its potential side effects, how to use it and more. These guides also answer the question, "how long Lexapro stay in system" if you're curious about the effects of this medication.
Zoloft is also an antidepressant. It contains the active ingredient sertraline and, like Lexapro, is part of a class of drugs called selective serotonin reuptake inhibitors.
As an SSRI, Zoloft works by increasing the amount of serotonin in your brain. It’s approved by the FDA to treat major depressive disorder, as well as the following conditions:
Post-traumatic stress disorder (PTSD)
Social anxiety disorder (SAD)
Panic disorder (PD)
Our guide to sertraline goes into more detail about how Zoloft works, its adverse effects and the steps that you can take to use it safely as a treatment for depression and anxiety symptoms.
It’s common and normal to switch antidepressants. In fact, many people with depression need to use several antidepressants before finding medication that’s the right match for their depressive symptoms and needs as an individual.
Your healthcare provider may recommend switching from Lexapro to Zoloft if:
You don’t experience any benefits from Lexapro after several weeks. It can take two to four weeks for most antidepressants to start working. However, some people may not experience benefits even after using their antidepressant medication consistently.
If you’ve used Lexapro for several weeks but don’t feel any improvements to your mood, sleep habits or mental wellbeing, your healthcare provider may recommend switching to Zoloft or a similar medication.
You have severe or persistent side effects from Lexapro. Side effects can occur with all antidepressants, including different SSRIs, but some are more likely to trigger certain side effects than others.
If you get persistent, severe or unpleasant side effects from Lexapro, switching to Zoloft or another medication may help to improve your quality of life.
You have a mental health disorder that Lexapro isn’t approved to treat. Lexapro is currently approved by the FDA as a treatment option for major depressive disorder and generalized anxiety disorder.
If you have panic disorder, social anxiety disorder or another mental health condition for which Lexapro isn’t approved, your healthcare provider may recommend that you switch to Zoloft to properly address your symptoms.
If you’re switching medications, make sure to follow your healthcare provider’s instructions and complete the process step by step. It’s important not to change medications or stop taking your medication on your own, as this may increase your risk of developing side effects.
There are several ways to switch from Lexapro to Zoloft. Your healthcare provider may suggest cross-tapering, tapering down your dosage before starting the new medication, or carrying out a direct switch from one medication to the other.
Cross-tapering involves gradually reducing the dosage of your original medication (in this case, Lexapro) while slowly increasing the dosage of the new medication (Zoloft).
Tapering your dosage involves gradually reducing the amount of Lexapro you take, then starting treatment with Zoloft at a low to moderate dosage. Your dosage of Zoloft may gradually increase over time based on your needs and response to the medication.
Direct switching involves changing from one medication to the other without a tapering process, gradual dosage increase or "wash-out" period.
Most of the time, switching from Lexapro to Zoloft involves tapering your Lexapro dosage over the course of several days or weeks, then beginning treatment with Zoloft at a low or moderate dosage. The same approach is typically used to switch from Zoloft to Lexapro.
Your healthcare provider will give you clear instructions to follow during the process of switching medications. Make sure to follow them closely and let your healthcare provider know if you have any questions or concerns.
It’s especially important to inform your healthcare provider if you feel any withdrawal symptoms during the switching process.
Withdrawal symptoms can happen when you abruptly stop taking an antidepressant. If you stop taking Lexapro without carefully tapering your dosage, you may start to experience the following withdrawal symptoms:
Irritability
Agitation
Mood changes
Dizziness
Confusion
Headache
Sweating
Shaking
Nausea
Tiredness
Anxiety
Abnormally excited moods
Tingling, burning or numbing in your hands or feet
Difficulty sleeping or staying asleep
Make sure to inform your healthcare provider as soon as you notice withdrawal symptoms. Your healthcare provider may adjust your dosage or make changes to the tapering process to reduce your risk of dealing with severe or persistent issues while changing antidepressants.
As SSRIs, Lexapro and Zoloft have a lower risk of causing side effects or drug interactions than older antidepressants, such as tricyclic antidepressants (TCAs) or monoamine oxidase inhibitor (MAOI) medications.
However, Lexapro and Zoloft can both potentially cause side effects, including some issues that may have a negative impact on your wellbeing and quality of life.
Common side effects of Lexapro include:
Sweating
Dizziness
Nausea
Constipation
Diarrhea
Abdominal pain
Indigestion
Flu-like symptoms
Fatigue
Insomnia
Changes in appetite
Somnolence (sleepiness)
Rhinitis (nasal congestion)
Sinusitis (sinus inflammation)
Dry mouth
Lexapro may cause sexual side effects, including a reduced sex drive and anorgasmia (difficulty reaching orgasm). In men, Lexapro can cause erectile dysfunction (ED).
Common side effects of Zoloft include:
Visual impairment
Nausea
Diarrhea
Dry mouth
Heart palpitations
Upset stomach
Constipation
Vomiting
Fatigue
Dizziness
Tremors
Somnolence (sleepiness)
Decreased appetite
Insomnia
Agitation
Sweating
Like Lexapro and other SSRIs, Zoloft can cause sexual side effects, including weak sex drive, difficulty reaching orgasm and, in men, erectile dysfunction.
When used with other medications that increase serotonin levels, Lexapro and Zoloft can both contribute to a group of symptoms called serotonin syndrome.
Serotonin is a serious, potentially life-threatening condition that can occur when your serotonin levels become too high. It often presents as a fever, high blood pressure and an elevated heart rate. When severe, it can cause seizures, respiratory distress, coma and even death.
Certain medications may increase your risk of serotonin syndrome when used with Lexapro or Zoloft, including:
Other antidepressants
Amphetamines
Mood stabilizers, such as lithium
Synthetic opioid medications, such as tramadol
Supplements for depression, such as St. John’s wort
Some of these substances may remain in your body for several weeks after stopping treatment, creating a potential risk of serotonin syndrome.
To reduce your risk of side effects and/or drug interactions, make sure to inform your healthcare provider about all medications you currently use or have recently used before taking Lexapro or Zoloft, or switching from one medication to the other.
Your healthcare provider may recommend switching from Lexapro to Zoloft if Lexapro isn’t fully effective at controlling your depression symptoms, or if you have too many negative side effects from Lexapro.
It’s also quite common to switch from Zoloft to Lexapro. Switching antidepressants several times is a normal aspect of treatment for major depression, and there’s no shame in switching if you’re not experiencing the full benefits from your current medication.
As part of the switching process, your healthcare provider will likely recommend slowly tapering your dosage of Lexapro, then starting with a low to moderate dosage of Zoloft.
Make sure to closely follow their dosage instructions to achieve success switching from Zoloft to Lexapro and minimize your risk of developing discontinuation symptoms.
Want to find out more about improving your mental health? We offer a complete range of mental health services online, including the ability to talk to a psychiatry provider and, if appropriate, get access to depression and anxiety medication online.
You can also learn more about dealing with depression, anxiety and other psychiatric disorders with our free online mental health resources and content.
Kate Hagerty is a board-certified Family Nurse Practitioner with over a decade of healthcare experience. She has worked in critical care, community health, and as a retail health provider.
She received her undergraduate degree in nursing from the University of Delaware and her master's degree from Thomas Jefferson University. You can find Katelyn on Doximity for more information.