Celexa vs. Zoloft: The Top 5 Differences Between These SSRI Antidepressants

Celexa (citalopram) and Zoloft (sertraline) are first-choice treatment options for depression, among other health conditions. They belong to a class of medications called selective serotonin reuptake inhibitors (SSRIs), and they work by raising levels of a chemical called serotonin in the brain.

Since they’re part of the same drug class, they have many similarities. This can make it difficult to choose one. Here, we’ll highlight the top five differences between Celexa and Zoloft to help make your decision easier.

1. Zoloft is FDA approved for more health conditions and age groups

Zoloft is FDA approved to treat multiple health conditions, including:

• Major depressive disorder (MDD), often referred to as simply “depression”

• Obsessive-compulsive disorder (OCD)

• Panic disorder

• Post-traumatic stress disorder (PTSD)

• Social anxiety disorder

• Premenstrual dysphoric disorder

Zoloft is typically prescribed to adults only. But for OCD, it can also be given to children as young as 6 years old.

Zoloft is also prescribed off-label to treat conditions such as generalized anxiety disorder, body dysmorphia, and binge-eating disorder. It can also treat premature ejaculation in men.

Celexa is often used to treat many of the same conditions as Zoloft. But it’s approved only for the treatment of MDD in adults. It’s used off-label to treat OCD, PTSD, and more.

2. Celexa and Zoloft come in different dosage forms

Celexa is available as 10 mg, 20 mg, and 40 mg tablets. The 20 mg and 40 mg tablets are scored, making it easier to cut them in half if needed. Its generic, citalopram, also comes as 30 mg capsules and a 10 mg/5 mL liquid solution. The liquid is a great option if you have trouble swallowing pills.

Zoloft comes as 25 mg, 50 mg, and 100 mg tablets, all of which are scored. It’s also available as a 20 mg/mL oral liquid. It’s important to note that the liquid must be diluted in 4 oz of a beverage before use and contains 12% alcohol. Water, lemon and lime soda, and orange juice are all common diluent choices. Generic sertraline comes in capsules too.

3. Celexa and Zoloft have different side effect profiles

Even though they’re in the same medication class, Celexa and Zoloft have different side effect profiles.

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Celexa

A relatively common side effect of Celexa is delayed ejaculation in men. It occurred in roughly 5% of those who took the medication in clinical trials. Other side effects — some occurring only at higher medication doses — include:

• Nausea

• Dry mouth

• Excessive sweating

• Drowsiness

• Insomnia

• Decreased sex drive

• Yawning

Zoloft

Zoloft’s initial studies had a slightly higher rate of side effects. In clinical trials, these side effects were reported in at least 5% of people taking Zoloft:

• Nausea

• Indigestion

• Diarrhea

• Tremors

• Excessive sweating

• Low appetite

• Decreased sex drive

• Ejaculation failure

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Shared side effects

Although more serious side effects are rare, all SSRIs have the potential to cause them. These may include:

• Manic episodes

• Higher risk of bleeding

• Serotonin syndrome

• Changes in heart rhythm

• Seizures

• Glaucoma

• Low sodium

• Suicidal thoughts or thoughts of self-harm

• Discontinuation syndrome, which is a combination of side effects that can happen from stopping the medication too quickly

Does Celexa cause more weight gain than Zoloft?

Celexa and Zoloft both have a “medium” potential to cause weight gain. But weight gain seems to be slightly less common with Zoloft. For instance, one study compared weight gain over 6 months across different SSRIs. It showed that people taking Celexa gained about 0.26 lbs (0.12 kg) more than those taking Zoloft. Zoloft has even been reported to cause weight loss in some cases.

4. Each has its own drug interaction concerns

Celexa and Zoloft have different drug interactions. This is largely because they’re metabolized (broken down) in the body in different ways. Liver enzymes called cytochrome P450 (CYP) enzymes are responsible for their metabolism, and there are many kinds of them.

Celexa

CYP2C19 inhibitors: Celexa is mostly metabolized by the CYP2C19 enzyme in the liver. It interacts with medications that interfere with this enzyme, such as omeprazole (Prilosec) and cimetidine (Tagamet HB). If this enzyme can’t break down Celexa like normal, citalopram levels in the body will rise. This can cause unwanted side effects. It’s recommended to take a lower dose of Celexa if you’re also taking a CYP2C19 inhibitor.

Zoloft

Medications metabolized by CYP2D6: Zoloft is a CYP2D6 inhibitor. It can block the breakdown of medications that are metabolized by this enzyme. Examples include metoprolol (Lopressor, Toprol XL), dextromethorphan (Robitussin, Delsym), and tolterodine (Detrol). When taken together, Zoloft can cause the levels of these medications to rise. This can lead to new or worsening side effects.

Phenytoin: Phenytoin (Dilantin) has a narrow therapeutic index, meaning there’s a small difference between a safe dose and a risky dose. A slight rise can lead to dangerous effects. Zoloft can raise phenytoin levels. A healthcare professional will likely want to monitor phenytoin levels when starting Zoloft or when changing your dose.

“Protein-bound” medications in the bloodstream: Zoloft naturally binds to certain proteins in the bloodstream. If you take another protein-bound medication that also does this, such as warfarin, the medications will compete for the protein. Medications are more active when they’re not attached to proteins in the blood, so this increases the risk of side effects.

Shared interactions

In practice, Celexa and Zoloft share several of the same interaction concerns.

Pimozide: You shouldn’t take this antipsychotic while taking Celexa or Zoloft. Both SSRIs can amplify pimozide levels. Pimozide, like phenytoin, has a narrow therapeutic index. A slight rise can lead to dangerous effects, including abnormal heart rhythms.

Monoamine oxidase inhibitors (MAOIs): You shouldn’t combine SSRIs with MAOIs, such as linezolid, selegiline, or methylene blue. These medications can lead to a condition called serotonin syndrome when taken together. Symptoms may include agitation, hallucinations, sweating, and more. If you’re taking an SSRI and need to start a MAOI, or vice versa, it’s recommended to stop one medicine and wait 14 days before starting the other.

Other medications that affect serotonin: Other medications and supplements can also lead to serotonin syndrome when paired with an SSRI. Top examples include:

• Tricyclic antidepressants, such as imipramine

• Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta)

• Opioids, such as oxycodone (OxyContin)

• Lithium (Lithobid)

• Amphetamines, such as Adderall

• Triptans, such as sumatriptan (Imitrex)

• St. John’s wort

Medications that increase bleeding risk: Celexa and Zoloft can increase the risk of bleeding. This is especially the case if you’re taking other medications that also increase bleeding risk, such as anticoagulants (blood thinners) or antiplatelets.

Medications that cause QT prolongation: Celexa and Zoloft can contribute to QT prolongation, a type of abnormal heartbeat. This can lead to abnormal heart rhythms, which can be dangerous. Your risk is higher if you take multiple QT-prolonging medications, including pimozide, ziprasidone (Geodon), and amiodarone (Pacerone).

5. Zoloft may be preferred while breastfeeding

It’s typically OK to take Celexa or Zoloft while breastfeeding. Zoloft, however, is generally favored.

Studies have found that less Zoloft passes into breastmilk than Celexa. It’s also been reported that breastfed infants who’ve been exposed to Celexa experienced side effects such as weight loss, irritability, and drowsiness. If you’re taking Celexa and plan on breastfeeding, you may want to check in with your prenatal care team to see if it’s necessary to switch medications.

How to save on Celexa and Zoloft

Celexa and Zoloft are available as brand-name medications. But you can also find them as lower-cost generics. GoodRx can help you navigate ways to save on your prescription.

• Save with GoodRx: A 1-month supply of generic citalopram at certain pharmacies costs as low as $5.66 with a free GoodRx coupon. The price of generic sertraline at certain pharmacies is as low as $9.42 with a free GoodRx coupon.

• Save with a copay savings card: If you have commercial insurance and meet eligibility requirements, brand-name Zoloft’s price is as little as $4 per month if you use the manufacturer’s savings card. You may also be able to pay as little as $10 per month for generic citalopram 30 mg capsules or generic sertraline 150 mg or 200 mg capsules.

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Written by:

Jenna Clayton, PharmD

Jenna Clayton, PharmD earned her Doctor of Pharmacy degree at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences in Buffalo, New York. Throughout her doctoral program, Jenna gained experience in a variety of pharmaceutical settings, including community, hospital, long-term care, and ambulatory care settings.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Renad Abu-Sawwa, PharmD, BCPPS

Renad Abu-Sawwa, PharmD, BCPPS, is an associate professor and associate discipline director of clinical pharmacology at Rush Medical College with a practice site as a clinical pharmacy specialist practitioner at RUSH Children's Hospital in the Pediatric Epilepsy Clinic.

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For additional resources or to connect with mental health services in your area, call the Substance Abuse and Mental Health Services Administration National Helpline at 1-800-662-4357. For immediate assistance, call the National Suicide Prevention Lifeline at 988, or text “HOME” to 741-741 to reach the Crisis Text Line.