Zoloft (sertraline) is a prescription drug that’s used to treat depression and other conditions. This drug can interact with other medications, including NSAIDs, some other antidepressants, and blood thinners.

Zoloft is used to treat the following conditions:

An interaction can occur because one substance causes another substance to have a different effect than expected. Interactions can also occur if you have certain health conditions.

Keep reading to learn about Zoloft’s possible interactions. And for more information about Zoloft, including details about its uses, see this article.

Certain health conditions or other factors could raise your risk of harm if you take Zoloft. In such cases, your doctor may not prescribe Zoloft for you. These are known as contraindications. The list below includes contraindications of Zoloft.

If you take a monoamine oxidase inhibitor: Using Zoloft with a monoamine oxidase inhibitor (MAOI) raises your risk of serotonin syndrome. (Like Zoloft, MAOIs are a type of antidepressant. But Zoloft is not an MAOI.)

With serotonin syndrome, you have a high level of a chemical called serotonin in your body. This can cause symptoms such as muscle rigidity, twitching muscles, and fast heart rate. In rare cases, serotonin syndrome can be life threatening.

Any MAOI can interact with Zoloft. A few examples of MAOIs include:

  • linezolid (Zyvox)
  • selegiline (Emsam, Zelapar)
  • phenelzine (Nardil)
  • isocarboxazid (Marplan)
  • methylene blue (ProvayBlue)

Due to this risk, doctors typically won’t prescribe Zoloft with an MAOI. If you’re taking an MAOI, your doctor will have you stop taking it at least 14 days before you start taking Zoloft.

If you have other questions about Zoloft and MAOIs, talk with your doctor or pharmacist.

If you take pimozide: Taking Zoloft with the drug pimozide can cause an atypical heart rhythm. Because of this risk, doctors usually avoid prescribing Zoloft with pimozide. Your doctor will likely suggest using a treatment other than Zoloft if you need to take pimozide.

If you take disulfiram and are prescribed the Zoloft liquid solution: Taking the liquid solution form of Zoloft with the drug disulfiram raises your risk of certain side effects, such as nausea and vomiting. (Disulfiram is prescribed to treat alcohol use disorder and can cause these side effects if you drink alcohol while taking it. And the Zoloft liquid solution contains alcohol).

Due to this risk, doctors will usually avoid prescribing Zoloft liquid solution if you’re taking disulfiram. Talk with your doctor to learn about other treatments that may be better options for you.

If you’ve had an allergic reaction: If you’ve had an allergic reaction to Zoloft or any of its ingredients, your doctor likely won’t prescribe Zoloft. This is because taking the drug could cause another allergic reaction. You can ask your doctor about other treatments that may be better options for you.

Before you start taking Zoloft, talk with your doctor if any of the factors above apply to you. Your doctor can determine whether Zoloft is safe for you to take.

Zoloft isn’t known to interact with alcohol. But combining Zoloft and alcohol could raise your risk of certain side effects. Examples include:

If you drink alcohol, talk with your doctor about how much (if any) is safe to consume while you’re taking Zoloft.

Before you start taking Zoloft, tell your doctor and pharmacist about any prescription, over-the-counter, or other drugs you take. Sharing this information with them may help prevent possible interactions. (To learn whether Zoloft interacts with supplements, herbs, and vitamins, see the “Are there other interactions with Zoloft?” section below.)

If you have questions about drug interactions that may affect you, talk with your doctor or pharmacist.

The chart below lists drugs that may interact with Zoloft. Keep in mind that this chart does not include all drugs that may interact with Zoloft. For more information about some of these interactions, see the “Drug interactions explained” section below.

Drug group or drug nameDrug examplesWhat can happen
nonsteroidal anti-inflammatory drugs (NSAIDs)aspirin
• ibuprofen naproxen (Aleve)
can increase the risk of side effects of NSAIDs and Zoloft
doxylamine (Nyquil)can raise the risk of side effects of Zoloft and Nyquil
bupropion hydrochloride (Wellbutrin)can increase the risk of side effects of Zoloft and Wellbutrin
other selective serotonin reuptake inhibitors (SSRIs)*• escitalopram (Lexapro)
• fluoxetine (Prozac)
can raise the risk of side effects of Zoloft and SSRIs
serotonin-norepinephrine reuptake inhibitors (SNRIs)• duloxetine (Cymbalta)
• venlafaxine (Effexor ER)
can increase the risk of side effects of Zoloft and SNRIs
other drugs that can affect serotonin (a chemical in your brain)• amphetamine/dextroamphetamine (Adderall, Adderall XR)
fentanyl
trazodone
• rizatriptan
tramadol
methadone
can increase the risk of side effects of Zoloft and other drugs
certain drugs that can cause a heart problem called long QT syndrome• certain antipsychotics, including quetiapine (Seroquel)
• certain antibiotics, including clarithromycin
• certain antiarrhythmics, including sotalol (Betapace)
can increase the risk of side effects of Zoloft and drugs that cause long QT interval
buspironecan increase the risk of side effects of Zoloft and buspirone
aspirin/acetaminophen/caffeine (Excedrin)can raise the risk of side effects of Zoloft and Excedrin
tricyclic antidepressants (TCAs)amitriptylinecan increase the risk of side effects of Zoloft and TCAs
monoamine oxidase inhibitors (MAOIs)• linezolid (Zyvox)
• selegiline (Emsam, Zelapar)
• phenelzine (Nardil)
can increase the risk of side effects of Zoloft and MAOIs
pimozidecan increase the risk of side effects from Zoloft and pimozide
blood thinnerswarfarin (Jantoven)
clopidogrel (Plavix)
can increase the risk of side effects from Zoloft and the blood thinner
antiseizure drugs
phenytoin (Dilantin)
• fosphenytoin (Cerebyx)
can increase the risk of side effects from antiseizure drugs
drugs broken down by the enzyme (protein) CYP2D6• atomoxetine (Strattera)
propafenone (Rythmol SR)
metoprolol (Lopressor, Toprol XL)
• dextromethorphan (Delsym)
can increase the risk of side effects from the other drug

* Zoloft is an SSRI.

Learn more about certain drug interactions that can occur with Zoloft.

Interaction with Wellbutrin

Zoloft can interact with the drug bupropion hydrochloride (Wellbutrin).

Wellbutrin and Zoloft are both antidepressants, but Wellbutrin works differently than Zoloft. Plus, in addition to treating depression, Wellbutrin is also used to treat seasonal affective disorder (SAD).

What could happen

Taking Zoloft and Wellbutrin together raises the risk of seizures, a serious side effect of both Zoloft and Wellbutrin.

What you can do

If you’re prescribed Zoloft and also take Wellbutrin, make sure your doctor knows this. They may choose to prescribe a lower Zoloft dose. Or they may lower your Wellbutrin dose. In some cases, they may lower your doses of both drugs.

If you experience a seizure while taking Zoloft and Wellbutrin, your doctor will likely have you stop taking one or both medications.

Interaction with other selective serotonin reuptake inhibitors (SSRIs)

Zoloft is a type of antidepressant called a selective serotonin reuptake inhibitor (SSRI). There are many other SSRIs available. These drugs interact with each other if taken together.

Examples of SSRIs include:

What could happen

SSRIs raise the level of serotonin in your body. Taking more than one SSRI raises your risk for serotonin syndrome (a condition that can be life threatening in some cases).

Symptoms of serotonin syndrome can include:

In severe cases, serotonin syndrome can result in seizures and coma.

What you can do

Due to this risk, doctors typically avoid prescribing more than one SSRI at a time. Taking multiple SSRIs together can raise your risk of side effects. And combining SSRIs hasn’t been shown to work better for depression than using just one SSRI.

If you need more than one medication to treat your depression, your doctor can tell you more about other antidepressants that are safe to use with Zoloft.

If you have symptoms of serotonin syndrome while taking Zoloft, seek emergency medical attention right away.

Interaction with serotonin-norepinephrine reuptake inhibitors

Zoloft belongs to a group of drugs called SSRIs, which are antidepressants. Another similar group of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRIs) interact with SSRIs (including Zoloft).

Examples of SNRIs include:

What could happen

SSRIs and SNRIs both raise the levels of serotonin in your body. Taking an SSRI and an SNRI at the same time raises your risk of serotonin syndrome. This condition can be life threatening in some cases.

What you can do

Because of this risk, doctors usually avoid prescribing Zoloft with an SNRI. Besides raising your risk of certain side effects, this combination hasn’t been shown to be more effective for depression than using Zoloft or an SNRI on its own.

If you need more than one treatment for your depression, your doctor can prescribe another drug that’s safe to take with Zoloft.

Zoloft may have other interactions. They could occur with supplements, foods, vaccines, or even lab tests. See below for details. Note that the information below does not include all other possible interactions with Zoloft.

Does Zoloft interact with supplements?

Before you start taking Zoloft, talk with your doctor and pharmacist about any supplements, herbs, and vitamins you take. Sharing this information with them may help you avoid possible interactions.

Zoloft can interact with valerian root. Taking a valerian root supplement with Zoloft could increase the effects of each product. This could increase your risk of side effects, such as sleepiness.

If you have questions about interactions that may affect you, talk with your doctor or pharmacist.

Zoloft interactions with herbs

Taking the herb St. John’s wort with Zoloft increases your risk of serotonin syndrome. (St. John’s wort is an herbal supplement taken to improve mood). For this reason, your doctor may suggest that you stop taking St. John’s wort during your Zoloft treatment.

Zoloft and vitamins

There are currently no reports of Zoloft interacting with vitamins. But this doesn’t mean that vitamin interactions won’t be recognized in the future.

For this reason, it’s still important to check with your doctor or pharmacist before taking any of these products while taking Zoloft.

Does Zoloft interact with food?

It’s possible that grapefruit or grapefruit juice interacts with Zoloft. But if these two substances do interact, it isn’t thought to be a serious interaction.

Grapefruit and grapefruit juice may block your body from breaking down Zoloft after you take a dose. But it’s not known whether this interaction is strong enough to raise your risk of side effects.

If you consume grapefruit or grapefruit juice and you’re prescribed Zoloft, it’s recommended that you do not change your grapefruit intake. And if you do consume more or less grapefruit or grapefruit juice, let your doctor know. They may want to adjust your Zoloft dosage.

Does Zoloft interact with vaccines?

There are currently no reports of Zoloft interacting with vaccines.

If you have questions about receiving vaccines while you’re taking Zoloft, talk with your doctor.

Does Zoloft interact with lab tests?

Zoloft may interact with urine screens that check for drugs called benzodiazepines, such as alprazolam (Xanax).

Specifically, taking Zoloft may cause a false positive on these tests. (A false positive means the test showed benzodiazepines in the urine, even if the person was not actually taking benzodiazepines).

If you’re taking Zoloft and need to undergo a urine test that checks for benzodiazepines, talk with your doctor. They can order other lab tests that check for these drugs and don’t interact with Zoloft.

Does Zoloft interact with cannabis or CBD?

There are currently no reports of Zoloft interacting with cannabis (commonly called marijuana) or cannabis products such as cannabidiol (CBD). But as with any drug or supplement, talk with your doctor before using cannabis with Zoloft.

Note: Cannabis is illegal at a federal level but is legal in many states to varying degrees.

Certain medical conditions or other health factors may raise the risk of interactions with Zoloft. Before taking Zoloft, talk with your doctor about your health history. They’ll determine whether Zoloft is right for you.

Health conditions or other factors that might interact with Zoloft include:

Suicidal thoughts or behaviors: If you have a history of suicidal thoughts or behaviors, talk with your doctor before starting Zoloft treatment. Zoloft has a boxed warning about this risk. This is the most serious warning from the Food and Drug Administration (FDA). For more information, see “Boxed warnings” at the top of this article.

Bleeding problems: If you have bleeding or clotting problems, such as hemophilia, be sure your doctor knows this before you start Zoloft. Zoloft can increase your risk of bleeding. Your doctor can determine whether it’s safe to prescribe Zoloft for your condition.

Narrow eye angles: If you have narrow eye angles, be sure to discuss this with your doctor before starting Zoloft. Zoloft can cause dilated pupils, which can lead to closed-angle glaucoma in people who have narrow eye angles. Closed-angle glaucoma is a medical emergency that can cause eye pain and vision loss in some cases. Your doctor may recommend having an eye exam before starting Zoloft.

Bipolar disorder: Zoloft can cause mania or hypomania, which are symptoms of bipolar disorder. If you’ve received a diagnosis of bipolar disorder, taking Zoloft could worsen your symptoms. Your doctor will likely screen you for bipolar disorder before prescribing Zoloft. If you have this condition, your doctor will likely recommend a treatment other than Zoloft.

Heart problems: Taking Zoloft can cause an atypical heart rhythm. Your risk of this side effect may be higher if you have an existing heart problem, such as heart failure, or if you’ve had a heart attack. Talk with your doctor to learn whether Zoloft is safe to take with your heart condition.

Liver problems: If you have a liver problem, tell your doctor before you begin taking Zoloft. Examples of liver problems include alcohol-related liver disease and liver failure. Doctors often prescribe a lower dose of Zoloft for people with mild liver problems. But your doctor may not prescribe Zoloft if your liver problem is considered moderate or severe. Instead, they can discuss safer treatment options with you.

Low blood sodium level: Like many other antidepressants, Zoloft can cause a low blood sodium level. If your sodium level is already low, taking Zoloft could worsen your condition. Your doctor may want to treat your low sodium level before prescribing Zoloft. Or they may choose to treat your low sodium level while you’re taking Zoloft.

Seizures: It isn’t known whether Zoloft is safe to take if you have epilepsy or another condition that causes seizures. People who experience seizures weren’t included in Zoloft’s studies. To find out whether Zoloft is safe to take with your condition, talk with your doctor.

Pregnancy: Doctors usually recommend taking Zoloft during pregnancy only if the benefits outweigh the risks. Zoloft may not be safe to take during the last 3 months of pregnancy. Talk with your doctor to learn more about safe treatments for your condition if you’re pregnant or planning to become pregnant.

If you do take Zoloft while pregnant, consider enrolling in this pregnancy registry for antidepressants. This registry collects details about how drugs such as Zoloft affect pregnancy. To learn more, call 866-961-2388 or talk with your doctor.

Breastfeeding: It’s not known whether it’s safe to take Zoloft while breastfeeding. Zoloft passes into breast milk in small amounts. But side effects reported in children who are breastfed have been rare. If you’re breastfeeding or planning to breastfeed, talk with your doctor about your options.

Allergic reaction: If you’ve had an allergic reaction to Zoloft or any of its ingredients, your doctor will likely not prescribe Zoloft. This is because taking the drug could cause another allergic reaction. You can ask your doctor about other treatments that may be better for you.

Help is out there

If you or someone you know is in crisis and considering suicide or self-harm, please seek support:

If you’re calling on behalf of someone else, stay with them until help arrives. You may remove weapons or substances that can cause harm if you can do so safely.

If you are not in the same household, stay on the phone with them until help arrives.

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Find answers to some frequently asked questions about Zoloft and possible interactions.

Is it safe to take Zoloft if I’m also taking Xanax?

It should be safe to take Zoloft with alprazolam (Xanax), although this isn’t known for certain.

Based on how the drugs work, Zoloft may block your body’s ability to break down Xanax as it should. This interaction was shown in studies of the two drugs in a lab but not in studies of people. So it’s not known what effects, if any, this interaction has in people taking these drugs together.

It’s not uncommon to take Zoloft and Xanax together. In fact, doctors sometimes prescribe Xanax short term when people first begin taking an antidepressant, including Zoloft. This is because antidepressants like Zoloft usually take several weeks or months to fully work to treat depression.

Alprazolam works right away, so it can help treat anxiety symptoms related to depression before Zoloft starts working. (Doctors will try and avoid prescribing Xanax long term for anxiety, though, due to the risk of side effects.)

If you’re prescribed Zoloft and are taking Xanax, let your doctor know. This combination is typically safe to take. But your doctor will likely want you to watch for changes in coordination, confusion, or other symptoms that affect your thinking or physical movement.

Can I take Zoloft if I’m also taking Pepcid?

Yes, it’s considered safe to take Zoloft with famotidine (Pepcid). There’s no known interaction between these drugs.

Pepcid is used to treat heartburn, gastroesophageal reflux disease (GERD), and other similar conditions that involve having too much stomach acid.

If you have other questions about taking Zoloft and Pepcid together, talk with your doctor or pharmacist.

Taking certain steps can help you avoid interactions with Zoloft. Before starting treatment, talk with your doctor and pharmacist. Things to discuss with them include:

  • Whether you drink alcohol or use cannabis.
  • Other medications you take, as well as any vitamins, supplements, and herbs. Your doctor or pharmacist can help you fill out a medication list.
  • What to do if you start taking a new drug during your Zoloft treatment.

It’s also important to understand Zoloft’s label and other paperwork that may come with the drug. Colored stickers that describe interactions may be on the label. And the paperwork (sometimes called the patient package insert or medication guide) may have other details about interactions. (If you didn’t get paperwork with Zoloft, ask your pharmacist to print a copy for you.)

If you have trouble reading or understanding this information, your doctor or pharmacist can help.

Taking Zoloft exactly as prescribed can also help prevent interactions.

Zoloft is prescribed to treat clinical depression and several other mental health conditions. If you still have questions about Zoloft and its possible interactions, talk with your doctor.

Questions you may want to ask your doctor include:

  • If I’m currently taking a medication that shouldn’t be used with Zoloft, how will we determine the best treatment plan for me?
  • Do I need to tell you if I start taking another medication or supplement during my Zoloft treatment?
  • Could I still take Zoloft even if it interacts with a health condition I have?

To learn more about Zoloft, see these articles:

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.