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Zoloft vs. Prozac: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

If you are experiencing or living with depression, your doctor may recommend an SSRI medication to help. SSRI, or selective serotonin reuptake inhibitor, drugs work by increasing the activity of serotonin in the brain. By increasing the level of serotonin, the medication can help balance feelings of mood and well-being.

Zoloft (sertraline) and Prozac (fluoxetine) are two SSRI prescription drugs that can treat mental health conditions like depression, panic disorder, and obsessive compulsive disorder (OCD). Although they are two of several different SSRI antidepressants, they have some similarities and differences.

What are the main differences between Zoloft vs. Prozac?

Zoloft is the brand name for sertraline hydrochloride. While Pfizer manufactures the brand name medication, there are also generic versions available. Zoloft is a commonly prescribed antidepressant that is approved for other conditions such as post-traumatic stress disorder (PTSD) and premenstrual dysphoric disorder (PMDD). It is available as an oral tablet or liquid solution.

Prozac is the brand name for fluoxetine. Brand-name Prozac is manufactured by Eli Lilly although generic versions are also available. Besides depression, panic disorder, and OCD, Prozac is also approved for bulimia nervosa, an eating disorder. Prozac is prescribed as a delayed-release oral capsule.

RELATED: Zoloft details | Prozac details | Sertraline Hydrochloride details | Fluoxetine details 

Main differences between Zoloft vs. Prozac
Zoloft Prozac
Drug class Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitor
Brand/generic status Brand and generic Brand and generic
What is the generic name?
What is the brand name?
What form(s) does the drug come in? Oral tablet
Oral solution
Oral capsule,
What is the standard dosage? 50 mg per day 20 mg once per day
How long is the typical treatment? Long term depending on the condition being treated Long term depending on the condition being treated
Who typically uses the medication? Children 6 years and older (OCD); Adults Children 8 years and older (depression); Adults 

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Conditions treated by Zoloft vs. Prozac

Zoloft is primarily used for the treatment of depression, OCD, panic disorder, and premenstrual dysphoric disorder. It is also approved to treat PTSD and social anxiety disorder.

Prozac is approved to treat major depression, OCD, panic disorder, and bulimia. While Prozac can be used to treat premenstrual dysphoric disorder, it’s marketed under a different name: Sarafem. Prozac can also treat depressive episodes in those with bipolar I disorder. Prozac can be used off-label for PTSD and social anxiety disorder.

Both Zoloft and Prozac can be used off-label to treat general anxiety, binge eating disorder, and body dysmorphic disorder.

Condition Zoloft Prozac
Major depression Yes Yes
Depression associated with bipolar I disorder No Yes
Obsessive compulsive disorder (OCD) Yes Yes
Panic disorder Yes Yes
Post-traumatic stress disorder (PTSD) Yes Off-label
Social anxiety disorder (SAD) Yes Off-label
Generalized anxiety disorder (GAD) Off-label Off-label
Premenstrual dysphoric disorder (PMDD) Yes Yes
Bulimia Off-label Yes
Binge eating disorder Off-label Off-label
Body dysmorphic disorder Off-label Off-label

Is Zoloft or Prozac more effective?

Zoloft and Prozac are similarly effective for treating symptoms of depression. In a double-blind, clinical trial, both Zoloft and Prozac improved depression based on different scores for depression and anxiety as well as sleep. While both SSRIs were found to be effective, Zoloft was found to have lower severity of side effects. Out of 108 randomized patients, 9.6% of the group treated with sertraline discontinued the drug compared to 19.6% of the group treated with fluoxetine due to ineffectiveness.

In a study from the Journal of Affective Disorders, Zoloft and Prozac showed similar effectiveness in patients with depression and anxiety. The results from the study showed no significant differences in improvement and treatment with either drug. Paxil, or paroxetine, was also included in this study and was found to be comparable.

Because every individual is different, one drug may be more suitable than the other. Consult a healthcare professional to determine which SSRI will give you the best results. Sometimes, it is a matter of trial and error.

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Coverage and cost comparison of Zoloft vs. Prozac

Zoloft is usually covered by many insurance plans. Since it is available as a generic, the prices will often be quite reasonable. The average retail cost for Zoloft without insurance is around $34.99 for a 30-day supply. You can save more on Zoloft with a SingleCare discount card which can lower the price from $8-18.

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Prozac is usually started at a dose of 20 mg in a 30-day supply. It can be purchased without insurance for an average retail cost of around $11.18. With a SingleCare card, you can expect to only pay as low as $4 for a prescription. Prozac is available as a generic and is covered by most insurance plans.

  Zoloft Prozac
Typically covered by insurance? Yes Yes
Typically covered by Medicare? Yes Yes
Standard dosage 50 mg tablets 20 mg capsules
Typical Medicare copay $13 $12
SingleCare cost $8-18 $4-20

Common side effects of Zoloft vs. Prozac

Since both drugs are in the same class of medications, they both have similar side effects. These side effects are often mild and resolve on their own within weeks after starting treatment. However, if they don’t go away or worsen, you may be recommended a different SSRI. Consult your doctor to discuss any side effects you may experience.

The most common side effects associated with Zoloft are nausea, diarrhea, indigestion, and tremors. The most common side effects with Prozac include nausea, nervousness, dry mouth, and indigestion. Changes in weight such as weight gain or weight loss are also common.

Other side effects for SSRIs may include sexual dysfunction, decreased libido, or impotence. Insomnia and other problems with sleep can also occur. More severe adverse effects include serotonin syndrome, a rare set of symptoms that can arise especially if you are taking other medications that increase serotonin activity.

  Zoloft Prozac
Side Effect Applicable? Frequency Applicable? Frequency
Nausea Yes 26% Yes 22%
Diarrhea Yes 20% Yes 11%
Indigestion Yes 8% Yes 8%
Dry Mouth Yes 14% Yes 9%
Constipation Yes 6% Yes 5%
Vomiting Yes 4% Yes 3%
Fatigue Yes 12% Yes N/A
Dizziness Yes 12% Yes 9%
Somnolence Yes 11% Yes 12%
Tremor Yes 9% Yes 9%
Insomnia Yes 20% Yes 19%
Decreased libido Yes 6% Yes 4%
Agitation Yes 8% Yes 2%
Palpitations Yes 4% Yes 1%

Source: DailyMed (Zoloft), DailyMed (Prozac)

Drug interactions of Zoloft vs. Prozac

As SSRI antidepressant drugs, Zoloft and Prozac interact with many of the same drugs. Both medications can interact with monoamine oxidase inhibitors (MAOI) and increase the risk of serotonin syndrome. Zoloft and Prozac should not be used with linezolid or intravenous methylene blue for the same reason.

Zoloft and Prozac can block the action of the CYP2D6 liver enzyme. Other drugs that are processed by this enzyme can interact with Zoloft and Prozac. These drugs include antipsychotics, benzodiazepines, antiarrhythmics, and some antidepressant drugs.

Zoloft and Prozac can interact with blood thinners such as aspirin and warfarin. Taking these medications together can increase the risk of bleeding. Consult a doctor for possible drug interactions with SSRIs.

Drug Drug Class Zoloft Prozac
Monoamine oxidase inhibitors (MAOI) Yes Yes
Antipsychotic Yes Yes
Opioids Yes Yes
Tricyclic antidepressant Yes Yes
Serotonin-norepinephrine reuptake inhibitors (SNRIs) Yes Yes
St. John’s Wort Herbal Yes Yes
Triptan Yes Yes
Antiepileptic Yes Yes
Lithium Mood stabilizer Yes Yes
NSAIDs Yes Yes
Warfarin Anticoagulant Yes Yes

*Consult a healthcare professional for other drug interactions

Warnings of Zoloft vs. Prozac

Antidepressants can increase the risk of suicidal thoughts in young adults and children. Suicidal thoughts and behaviors should be monitored in individuals whose symptoms are not improving.

Zoloft and Prozac can lower the seizure threshold in some people who have a history of seizures. Therefore, these drugs should be monitored or avoided in those affected groups.

Zoloft and Prozac can cause QT prolongation, an electrical disturbance in the heart muscle. If you have a history of arrhythmias or abnormal heart rhythm, you may be at an increased risk.

SSRI antidepressant drugs are usually prescribed for long-term uses. Abruptly stopping these medications can cause withdrawal symptoms such as rebound anxiety, headaches, and insomnia. When stopping these medications, they should be tapered slowly with proper medical guidance.

Zoloft and Prozac are in Pregnancy Category C. They should only be used if benefits outweigh the potential pregnancy risks. Consult a doctor if you are pregnant or breastfeeding.

Frequently asked questions about Zoloft vs. Prozac

What is Zoloft?

Zoloft is an SSRI antidepressant medication that is used to treat depression and other mental health disorders. It can also be prescribed for OCD in adults and children aged 6 years or older. Zoloft is usually started at a dose of 50 mg once per day.

What is Prozac?

Prozac is an SSRI antidepressant that can treat depression, panic disorder, and OCD. It is also approved to treat bulimia and depression associated with bipolar disorder. It can be prescribed for depression in adults and children aged 8 years and older as well as OCD in adults and children aged 7 years and older.

Are Zoloft vs. Prozac the same?

No. Zoloft and Prozac are not the same. Although they both work to enhance serotonin activity, they have some different approved uses. Zoloft is FDA approved for PTSD and social anxiety disorder whereas Prozac is used off-label for these indications. Zoloft is available as an oral tablet and liquid solution. Prozac only comes as an oral capsule.

Is Zoloft vs. Prozac better?

Zoloft and Prozac are both comparable. Studies have shown no significant differences in treatment with the two. However, they may have different side effect profiles. One SSRI may be prescribed over the other depending on your symptoms.

Can I use Zoloft vs. Prozac while pregnant?

Zoloft and Prozac may be used during pregnancy if necessary. However, not enough studies have shown the effects of these drugs on babies. Consult your doctor if you are pregnant or breastfeeding.

Can I use Zoloft vs. Prozac with alcohol?

It is not recommended to drink alcohol while taking Zoloft or Prozac. Drinking alcohol with these medications can increase side effects such as dizziness and drowsiness.

Which SSRI has the least side effects?

Zoloft and Prozac are both well tolerated. Zoloft may produce more digestive and sexual side effects while Prozac may produce more headaches. Side effects from SSRIs are often mild and improve over time.

Is Prozac good for anxiety?

Yes. Prozac can be prescribed off-label for general and social anxiety. It may also be useful for people with both depression and anxiety.