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Zoloft (Sertraline) vs Prozac (Fluoxetine): Which is More Effective?

Kristin Hall, FNP

Reviewed by Kristin Hall, FNP

Written by Nicholas Gibson

Published 10/12/2020

Updated 09/13/2022

Prozac®, which contains the active ingredient fluoxetine, and Zoloft®, which contains sertraline, are two of the most widely used antidepressants available today.

Prozac and Zoloft are both selective serotonin reuptake inhibitors, or SSRIs. Both medications work by changing the level of serotonin -- a neurotransmitter that’s linked to depression -- that’s present in your brain.

We’ve explained more about how SSRIs such as Zoloft and Prozac work in our complete guide to selective serotonin reuptake inhibitors (SSRIs).

If you’ve recently been diagnosed with major depressive disorder or one of several other mental health conditions, your healthcare provider may suggest using Zoloft, Prozac or a similar type of antidepressant medication to control your symptoms. 

Zoloft and Prozac are both generally effective, but there are several differences between the two antidepressant drugs that you should be aware of before you start treatment. 

Below, we’ve talked about how Prozac and Zoloft work, as well as the main differences between these two medications. 

We’ve also listed side effects, drug interactions and other helpful information that you should be aware of before using either medication to treat depression, generalized anxiety disorder (GAD) or other mental health issues. 

  • Prozac and Zoloft are both antidepressants of the selective serotonin reuptake inhibitor (SSRI) class. These medications work by increasing the concentration of serotonin, an important neurotransmitter, throughout your brain and body.

  • Both medications are approved for use as treatments for depression. They may also be prescribed for other disorders, such as panic disorder or obsessive-compulsive disorder (OCD). Both medications are also prescribed off-label to treat other conditions.

  • Since both medications are SSRIs, Prozac and Zoloft tend to cause similar side effects and can interact with similar medications and supplements.

  • Prozac and Zoloft are both available as generic medications, meaning they’re typically very affordable. Prozac contains the active ingredient fluoxetine, while Zoloft contains sertraline.

  • Prozac and Zoloft can both cause antidepressant withdrawal symptoms when treatment is stopped abruptly. It’s important that you talk to your healthcare provider before making any changes to your dosage or discontinuing your use of either medication.

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As SSRIs, Prozac and Zoloft are prescribed to treat similar conditions, albeit with a few small differences and special uses for each drug. 

Currently, Prozac and Zoloft are both approved by the FDA to treat major depressive disorder (depression, or MDD), panic disorder (PD) and obsessive-compulsive disorder (OCD).

Prozac is also prescribed to treat the eating disorder bulimia nervosa. In combination with the antipsychotic medication olanzapine, it’s also prescribed to treat treatment resistant depression and acute depressive episodes associated with bipolar disorder, or bipolar depression.

Zoloft is also commonly prescribed off-label to treat post-traumatic stress disorder (PTSD) and social anxiety disorder (SAD).

In some cases, both medications are prescribed off-label to treat conditions unrelated to mental health. For example, sertraline is often prescribed off-label to improve sexual health in men with premature ejaculation (PE).

Use in Children and Teenagers

Prozac and Zoloft are commonly prescribed to adults. They’re also approved by the FDA for use in children and teenagers for certain mental health conditions:

  • Prozac, or generic fluoxetine, can be prescribed to children eight years of age or older as a treatment for major depressive disorder, and to children seven years or older as a treatment for obsessive compulsive disorder (OCD).

  • Zoloft, or generic sertraline, can be prescribed to children six years of age or older as a treatment for obsessive compulsive disorder (OCD).

It’s important to note that the FDA has issued “black box” warnings for both Zoloft and Prozac, noting that both medications can potentially increase the risk of suicidal thoughts and behavior in children, adolescents and young adults. 

They also insist parents, guardians and healthcare providers monitor these age groups closely for an increase in, or worsening of, suicidal thoughts. 

Prozac and Zoloft, as well as their generic equivalents, are both easy medications to take. Both are taken once daily in the morning or evening and typically need to be used for several months to reduce the severity of the symptoms of depression.

Fluoxetine, the active ingredient in Prozac, is available as a tablet, oral solution and standard or delayed-release capsule. If you’re prescribed Prozac or generic fluoxetine, you’ll need to take your medication one time per day, either in the morning or evening.

The standard initial dosage for fluoxetine is 20mg per day. Your healthcare provider may adjust your dosage to a maximum of 80mg daily if you have persistent or severe depression symptoms that don’t improve at a lower dosage.

Sertraline, the active ingredient in Zoloft, is also available as a tablet, oral solution or capsule. It should be taken one time per day in the morning or evening. 

The standard dosage range for sertraline is 50 to 200mg per day. Your healthcare provider will likely prescribe an initial dose of 50mg, then increase your dosage based on the severity of your symptoms and response to this medication.

Regardless of which antidepressant medicine you’re prescribed, you’ll need to keep using either Zoloft or Prozac for approximately six to eight weeks before you’ll typically notice improvements in your depression symptoms.

If you don’t notice any improvements after six to eight weeks of consistent use, it’s important to inform your mental health provider.

Prozac and Zoloft can both cause adverse effects. As with other SSRIs, the most common side effects of Prozac and Zoloft generally aren’t serious. 

However, although uncommon, both medications can potentially cause severe side effects and interactions that you should be aware of before using either medication for depression, anxiety or other conditions. 

Side Effects of Prozac (Fluoxetine)

Common side effects of Prozac and generic fluoxetine (affecting five percent of users or more and twice as many users as a non-therapeutic placebo) include:

  • Abnormal dreams

  • Abnormal ejaculation

  • Anorexia

  • Anxiety

  • Asthenia (loss of strength and energy)

  • Diarrhea

  • Dry mouth

  • Dyspepsia (indigestion)

  • Flu syndrome (fever, chills, headache and other flu-like symptoms)

  • Impotence (erectile dysfunction)

  • Insomnia

  • Nausea 

  • Nervousness

  • Pharyngitis (sore throat)

  • Rash

  • Reduced libido

  • Sinusitis (inflammation of the sinuses)

  • Somnolence (sleepiness or drowsiness)

  • Sweating

  • Tremor

  • Vasodilation

  • Yawning

Side Effects of Zoloft (Sertraline)

Common side effects of Zoloft and generic sertraline (affecting five percent of users or more and twice as many users as a non-therapeutic placebo) include:

  • Decreased appetite

  • Diarrhea

  • Difficulty or inability to ejaculate

  • Dyspepsia (indigestion)

  • Hyperhidrosis (excessive sweating)

  • Nausea

  • Reduced libido

  • Tremor

If you experience persistent or bothersome side effects while using either type of medication, it’s important to inform your healthcare provider. 

Serious Side Effects and Drug Interactions

Prozac and Zoloft are generally safe medications for most people. However, all antidepressants carry some risk of causing serious side effects. 

One potential side effect that’s important to be aware of is an increased risk of suicidal thoughts and behavior in children, teenagers and young adults. Prozac and Zoloft both carry a mandatory FDA warning notifying users of this risk in people aged 24 and under.

This risk is most significant during the first few months of treatment, or after changes are made to the medication’s dosage. Both medications may cause serotonin syndrome — a serious, potentially life-threatening side effect that can occur when they are used with other medications or supplements that increase serotonin levels.

Signs of elevated levels of serotonin include excessive sweating, high blood pressure, a fast or unusual heart rate, dilated pupils, shivering, tremor, jerky movements, an elevated temperature, hyperactive bowel sounds, excessive alertness and pressured speech.

In severe cases, serotonin syndrome can cause dramatic swings in pulse rate, seizures, muscle rigidity, renal failure, acute respiratory distress syndrome, coma and even death.

Your risk of serotonin syndrome is highest if you use Zoloft or Prozac with other antidepressants or anti-anxiety medications that affect serotonin levels, as well as herbal supplements for mental health such as St. John’s wort.

To reduce your risk of dangerous drug interactions, make sure to tell your mental health provider about all medications you take -- particularly medications that inhibit the reuptake of serotonin -- before using Zoloft, Prozac or their generic equivalents.

As SSRIs, both medications can also cause issues such as abnormal bleeding, or an increased risk of bleeding, particularly when used with certain blood thinners or NSAIDs.

Both medications can also interact with other drugs, including other antidepressants and widely used prescription medications.

Use During Pregnancy and Breastfeeding

Prozac and Zoloft, as well as their generic equivalents, are both classed as pregnancy category C medications.

This means that animal reproduction studies have shown adverse effects on fetuses, and that there is inadequate research regarding their safety in humans. However, the potential benefits of these medications may warrant their use during pregnancy in certain circumstances.

If you are pregnant or breastfeeding, or plan to become pregnant in the future, it’s important to talk to your healthcare provider if you’re currently prescribed either Prozac, Zoloft or a generic equivalent or either medication.

Zoloft and Prozac are both widely available as generic medications, meaning they’re affordable to purchase. 

We offer sertraline (Zoloft) and fluoxetine ( Prozac) via our online psychiatry service, following an online evaluation with a licensed psychiatry provider who will determine if either medication is appropriate for you. 

Generic forms of both antidepressants are covered under most insurance and Medicare plans, meaning you should be able to access medication if you have health insurance.

If you’d like to know more about your health insurance plan’s coverage for sertraline, fluoxetine and other psychiatric medications, it’s best to contact your provider and ask them about what’s covered under your plan. 

As some of the most widely-used prescription medications in the United States, Zoloft, Prozac and their generic equivalents are available from almost all pharmacies.

Prozac (fluoxetine) and Zoloft (sertraline) are both effective at treating depression. Research, including several studies, has shown that both medications produce improvements in people with major depression and anxious depression.

One study tested the clinical efficacy of fluoxetine, sertraline and paroxetine, another SSRI, in 104 patients experiencing major depression and anxious depression, and found no significant differences in the effectiveness of each medication.

Another meta-analysis of 132 randomized controlled trials found that fluoxetine showed slightly lower efficacy than sertraline for the treatment of depression.

However, the researchers behind this meta-analysis noted that although statistically significant, the clinical meaning of those differences isn’t completely certain.

Overall, both antidepressants show similar effectiveness in scientific research, as you’d expect from two medications in the same drug class. 

As mentioned above, Prozac and Zoloft are also prescribed to treat several other disorders and conditions. If you’re being treated for something other than depression, one medication may be a more suitable choice than the other. 

Your healthcare provider will select the most appropriate antidepressant for you based on your needs, symptoms and general health. 

While Prozac and Zoloft cause similar side effects, specific side effect rates can differ from one medication to the other.

If you get persistent or severe side effects from one medication, such as sexual dysfunction or nausea, your healthcare provider might suggest switching to the other, or to a different type of antidepressant. 

There’s no “best” antidepressant for everyone. It’s common and normal to try several different antidepressants with your healthcare provider before settling on the medication that best suits your symptoms and needs as an individual. 

Because of this, it’s difficult to say if you should take Zoloft, Prozac or any other specific type of antidepressant. Depression can cause a varied range of symptoms, and an antidepressant that works well for one person may not be effective for another.

If you’re prescribed Zoloft or Prozac and don’t feel like your medication is working properly after at least six weeks of use, it’s important to let your healthcare provider know.

They may recommend adjusting your dosage, changing the way you use your antidepressant or making other changes to your daily life. In some cases, they may advise you to switch from your current medication to a different type of SSRI or other antidepressant. 

Remember that finding the right antidepressant is often a process, and it may take several tries for you to find the medication that works best for you.

What Other Medications are Similar to Prozac and Zoloft?

Prozac and Zoloft are both selective serotonin reuptake inhibitors or SSRIs. There are several other medications in this class, such as Paxil® (paroxetine), Lexapro® (escitalopram), Celexa® (citalopram) and others. 

Other types of antidepressants can also offer benefits for depression, anxiety and other mental illnesses. 

Can Prozac or Zoloft Cause Weight Gain?

Many antidepressants are associated with weight gain. As SSRIs, both Prozac and Zoloft are less likely to cause significant weight gain than older types of antidepressant, such as tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs).

In a 2016 study, researchers found that people prescribed fluoxetine and sertraline both gained a small amount of weight (4.6lbs for fluoxetine and 10.5lbs for sertraline) over the course of two years of treatment.

In contrast, people prescribed the atypical antidepressant bupropion (Wellbutrin®) experienced a small degree of weight loss.

A separate study published in 2018 found that several of the most commonly prescribed SSRIs and other antidepressants, including the active ingredients in Prozac and Zoloft, were linked to an elevated risk of weight gain during treatment.

In short, antidepressants, including Prozac and Zoloft, can cause weight gain. However, not all people who are prescribed antidepressants will gain weight.

If you are concerned about weight gain while using either antidepressant, talk to your healthcare provider. If suitable for you, your healthcare provider may be able to prescribe an antidepressant that’s less likely to cause weight gain or help you to manage your weight during treatment. 

Is it Safe to Drink Alcohol While Using Prozac or Zoloft?

Drinking alcohol while you use either Prozac or Zoloft is not recommended. The FDA labels for both medications specifically recommend avoiding consuming any alcohol while you’re actively using either medication.

In addition to affecting the effectiveness of medication, drinking alcohol may increase your risk of experiencing side effects and/or worsen your depression.

What Else Should Be Avoided While Using These Medications?

Both Prozac and Zoloft can affect your ability to make decisions think clearly or react quickly. If you are prescribed either medication, it’s important not to drive, operate heavy machinery or do any other potentially dangerous tasks until you understand how the medication affects you.

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Editorial Standards

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references. See a mistake? Let us know at [email protected]!

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Kristin Hall, FNP

Kristin Hall is a board-certified Family Nurse Practitioner with decades of experience in clinical practice and leadership. 

She has an extensive background in Family Medicine as both a front-line healthcare provider and clinical leader through her work as a primary care provider, retail health clinician and as Principal Investigator with the NIH

Certified through the American Nurses Credentialing Center, she brings her expertise in Family Medicine into your home by helping people improve their health and actively participate in their own healthcare. 

Kristin is a St. Louis native and earned her master’s degree in Nursing from St. Louis University, and is also a member of the American Academy of Nurse Practitioners. You can find Kristin on LinkedIn for more information.

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