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

Zoloft vs. Prozac treat depression but they work in different ways. Compare the side effects and cost of these drugs to find out which one is better.

Zoloft vs. Prozac differences | Conditions treated | Forms and dosagesWhich drug is more effective? | Coverage and cost comparison | Common side effectsSerious side effectsInteractions | Warnings | FAQs

If you are 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 levels of serotonin, SSRIs may help improve mood and feelings of well-being. 

Zoloft (sertraline) and Prozac (fluoxetine) are SSRI prescription drugs that can treat mental health conditions like depression, panic disorder, and obsessive-compulsive disorder (OCD). Although they work similarly to SSRI antidepressants, Zoloft and Prozac have some important differences.

What are the main differences between Zoloft vs. Prozac?

Zoloft is the brand name for sertraline hydrochloride. Although many people may be familiar with the brand-name version manufactured by Pfizer,  a generic version of Zoloft is available. Zoloft is a commonly prescribed antidepressant that is approved for depression and 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, which is manufactured by Eli Lilly, is the brand name for fluoxetine. A generic version of Prozac is also widely available. In addition to depression, panic disorder, and OCD, Prozac is approved for bulimia nervosa, an eating disorder. Prozac is usually prescribed as an oral capsule taken daily. It is also available as a delayed-release oral capsule that is taken weekly. 

Zoloft Prozac
Drug class Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitor
Brand/generic status Brand and generic version available Brand and generic version available
What is the generic name?

What is the brand name?

Sertraline

Zoloft

Fluoxetine

Prozac

What form(s) does the drug come in? Oral tablet

Oral solution

Oral capsule

Oral capsule,

delayed-release

What is the standard dosage? 50 to 200 mg per day 20 to 80 mg 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

Conditions treated by Zoloft vs. Prozac

Zoloft is commonly prescribed for the treatment of major depressive disorder and social anxiety disorder. However, it is also approved to treat OCD, panic disorder, premenstrual dysphoric disorder, and PTSD. 

Prozac is often prescribed to treat major depressive disorder,  panic disorder, OCD, and bulimia. In addition, Prozac can treat  depressive episodes of bipolar I disorder when used with olanzapine. The active ingredient of Prozac can also be used to treat premenstrual dysphoric disorder, but it’s marketed under a different name: Sarafem. Prozac is sometimes used off-label for PTSD and social anxiety disorder. 

Off-label uses of Zoloft and Prozac also include the treatment of general anxiety, binge eating disorder, and body dysmorphic disorder.

Condition Zoloft Prozac
Major depressive disorder 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 nervosa Off label Yes
Binge eating disorder Off label Off label
Body dysmorphic disorder Off label Off label

Forms and dosages of Zoloft and Prozac

Although Zoloft and Prozac can be used to treat several of the same conditions, the dosage forms and dosage prescribed can vary. The dosage forms of a medication are an important aspect of treatment, as some people may have certain preferences. For example, a person with trouble swallowing capsules may prefer a liquid or oral solution. 

As with all SSRIs, it can take around four to six weeks for Zoloft and Prozac to be fully effective. If symptoms do not improve after six weeks of treatment, a healthcare provider may recommend adjusting the dosage or switching the antidepressant

Dosages vary depending on the condition being treated, the age of the person, and other factors. Always consult a healthcare provider for the most appropriate dosage plan. 

Forms and dosages of Zoloft

Zoloft comes as 25 mg, 50 mg, and 10 mg oral tablets. It is also available as a 20 mg/mL oral solution. 

For major depressive disorder, OCD, panic disorder, PTSD, and social anxiety disorder, a 25 to 50 mg dose of Zoloft is taken once daily at the start of treatment. The usual dosage for these conditions is 50 to 200 mg once daily. A healthcare provider may gradually increase the dosage in 25 to 50 mg increments each week until an adequate treatment response is reached. 

For premenstrual dysphoric disorder, the usual dosage of Zoloft is 50 to 100 or 150 mg once daily. However, the dosage for premenstrual dysphoric disorder depends on the phase of the menstrual cycle when Zoloft is taken. 

Forms and dosages of Prozac

For major depressive disorder, OCD, and panic disorder, Prozac is usually started at 10 to 20 mg once daily in the morning. For bulimia, Prozac is usually started at 60 mg in the morning. Prozac may cause insomnia if taken at bedtime, especially when treatment is first started. Therefore, healthcare providers typically recommend taking Prozac in the morning. If there is no treatment response with the starting dosage after several weeks, the dosage may be increased. 

Prozac can also help treat depressive episodes of bipolar I disorder and treatment-resistant depression when combined with an antipsychotic called olanzapine. The starting adult dosage for depressive episodes associated with bipolar I disorder and treatment-resistant depression is 20 mg of Prozac with 5 mg of olanzapine once daily in the evening. 

See the table below for a comparison of starting and usual dosages of Zoloft and Prozac for shared indications. 

Indication Zoloft dosage Prozac dosage
Major depressive disorder Starting dosage: 50 mg once daily

Usual dosage: 50 to 200 mg once daily

Starting dosage: 20 mg once daily in the morning

Usual dosage: 20 to 80 mg once daily in the morning

OCD Starting dosage: 50 mg once daily

Usual dosage: 50 to 200 mg once daily

Starting dosage: 20 mg once daily in the morning

Usual dosage: 20 to 60 mg once daily in the morning

Panic disorder Starting dosage: 25 mg once daily

Usual dosage: 50 to 200 mg once daily

Starting dosage: 10 mg once daily in the morning

Usual dosage: 20 mg once daily in the morning

Dosages may vary depending on  treatment response and tolerability of the drug. 

Dosages in specific populations

A lower dosage of Zoloft and Prozac may be recommended in elderly people or people with liver problems. However, in people with moderate or severe liver impairment, Zoloft is not recommended. The dosages of Zoloft and Prozac do not usually need to be adjusted in people with kidney impairment. 

Discontinuing treatment

When discontinuing Zoloft or Prozac, the dosage should be gradually decreased over time. The abrupt discontinuation of Zoloft or Prozac may cause withdrawal symptoms and other adverse effects, such as headaches, dizziness, agitation, and insomnia. 

Is Zoloft or Prozac more effective?

Zoloft and Prozac are similarly effective for treating symptoms of depression. Compared to placebo, Zoloft and Prozac have been shown to help alleviate symptoms and improve quality of life. 

One double-blind clinical trial found that Zoloft and Prozac improved  scores for depression and anxiety in over 100 participants. While both SSRIs caused similar side effects, patients taking Zoloft reported less severe side effects than patients taking Prozac. In addition, the study suggests that Zoloft is associated with better clinical improvement than Prozac. Nearly 10% of patients stopped taking Zoloft, and around 20% of patients stopped taking Prozac due to ineffectiveness. 

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

Because everyone may have different symptoms and respond to medications differently, one SSRI may be more suitable than another. Consult a healthcare professional to determine which SSRI will give you the best results. Sometimes, it is a matter of trial and error. 

Coverage and cost comparison of Zoloft vs. Prozac

Zoloft is usually covered by insurance plans. Since it is available as a generic, the prices will often be quite reasonable. However, the average retail cost of a 30-day supply of brand-name Zoloft is around $400. You may be able to save on Zoloft with a SingleCare discount card, which can help lower the cost of brand-name or generic Zoloft.

Prozac is available as a generic and is covered by most insurance plans. Although Prozac is covered by most insurance plans, insurance plans prefer to cover the generic version of the drug. A 30-day supply of brand-name Prozac can be purchased without insurance for an average cost of $600. Using a SingleCare card for Prozac may help lower the cash price of brand-name or generic Prozac. 

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 $0–$13 $0–$12
SingleCare cost $8–18 $4–20

Common side effects of Zoloft vs. Prozac

Since Zoloft and Prozac drugs are in the same class of medications, they both have similar side effects. Side effects from antidepressants are usually mild and resolve on their own within a couple of weeks after starting treatment. However, if side effects persist or worsen, you may be recommended a different dosage or medication. Consult your healthcare provider to discuss any side effects you may experience. 

The most common side effects associated with Zoloft include nausea, diarrhea, indigestion, and tremors. The most common side effects of Prozac include nausea, nervousness, dry mouth, and indigestion. Although Zoloft and Prozac can cause similar side effects, the severity of these side effects can differ. Studies suggest that fewer people taking Zoloft stop treatment due to side effects than people taking Prozac. 

Other possible side effects of SSRIs may include insomnia or other changes in sleep habits,  sexual dysfunction, such as decreased libido or impotence, and weight changes, such as weight gain or weight loss. 

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)

Serious/rare side effects of Zoloft and Prozac

Serious side effects are possible with SSRI antidepressants, including Zoloft and Prozac. It may be necessary to seek immediate medical attention if serious side effects occur, although side effects are rare. The risk of serious side effects is usually increased in people taking other medications or people with pre-existing medical conditions. 

Serotonin syndrome

Increased levels of serotonin may increase the risk of serotonin syndrome. People who take serotonergic drugs, such as SSRI antidepressants, may have an increased risk of serotonin syndrome, especially if other serotonergic drugs are being taken. However, serotonin syndrome is usually self-limiting and resolves on its own after discontinuing the serotonergic drug. Symptoms of serotonin syndrome can vary and may include agitation, delirium, tremors, high blood pressure, fever, and sweating. 

Allergic reactions

Allergic or hypersensitivity reactions have been reported with the use of Zoloft and Prozac. It’s important to seek medical attention if signs or symptoms of an allergic reaction arise, such as fever, rash, difficulty breathing, and swelling of the face or throat. 

Angle-closure glaucoma 

Angle-closure glaucoma is a serious eye problem that has been reported with the use of antidepressants, including Zoloft and Prozac. It is characterized by an increase in fluid pressure in the eye and can cause symptoms such as pain in the eye, blurry vision, and headache. Zoloft and Prozac can cause the pupils to dilate, which may trigger an angle closure attack.

Activation of mania/hypomania

Zoloft and Prozac may trigger mania or hypomania in individuals with bipolar disorder. Healthcare providers typically screen for bipolar disorder before prescribing an antidepressant like Zoloft or Prozac. 

Hyponatremia

Low sodium levels in the blood, or hyponatremia, may occur with the use of SSRIs, including Zoloft and Prozac. Symptoms of hyponatremia may include confusion, weakness, headache, and unsteadiness. Older people, people taking diuretics, and people who are volume-depleted may be at an increased risk of hyponatremia with these antidepressants. 

Bleeding

The use of SSRIs may increase the risk of bleeding events, such as peptic ulcers. The risk of bleeding may be increased when SSRIs are taken with blood thinners, including warfarin and aspirin. 

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 (MAOIs), which can lead to an increased risk of serotonin syndrome. Zoloft and Prozac should not be used with linezolid or intravenous methylene blue for the same reason. 

Zoloft and Prozac should not be taken with pimozide or thioridazine. Mixing Zoloft or Prozac with either of these drugs may increase the risk of an abnormal heart rhythm problem called QT prolongation. Zoloft and Prozac should be used cautiously with other drugs that may increase the risk of QT prolongation. 

Zoloft and Prozac can block the action of the CYP2D6 liver enzyme, which may lead to increased levels of certain drugs that are processed by this enzyme. These drugs include certain antipsychotics, antiarrhythmics, and antidepressants. 

Zoloft and Prozac can interact with blood thinners, such as aspirin and warfarin. Taking these medications together may increase the risk of bleeding. 

Consult a healthcare provider for medical advice on other possible drug interactions with SSRIs. 

Drug Drug Class Zoloft Prozac
Selegiline
Rasagiline
Isocarboxazid
Phenelzine
Monoamine oxidase inhibitor (MAOI) Yes Yes
Pimozide
Thioridazine
Antipsychotic Yes Yes
Fentanyl 
Tramadol
Opioid Yes Yes
Amitriptyline
Nortriptyline
Imipramine
Desipramine
Tricyclic antidepressant Yes Yes
Venlafaxine
Desvenlafaxine
Duloxetine
Serotonin-norepinephrine reuptake inhibitor (SNRI)  Yes Yes
St. John’s Wort Herbal Yes Yes
Sumatriptan
Zolmitriptan
Naratriptan
Triptan Yes Yes
Phenytoin
Fosphenytoin
Anticonvulsant Yes Yes
Lithium Mood stabilizer Yes Yes
Ibuprofen
Naproxen
Aspirin
NSAID 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 people who may be at risk of experiencing a seizure. 

Zoloft and Prozac can cause QT interval prolongation, caused by an electrical disturbance in the heart muscle that leads to an abnormal heart rhythm. Individuals with a history of arrhythmias may be at an increased risk of heart problems with Zoloft and Prozac. 

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

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

Frequently asked questions about Zoloft vs. Prozac

What is Zoloft?

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

What is Prozac?

Prozac is an SSRI antidepressant that can treat major depression, panic disorder, and OCD. It is also approved to treat bulimia and depression associated with bipolar disorder (when used with olanzapine). It can be prescribed for depression in adults and children aged eight years and older and OCD in adults and children aged seven years and older. Prozac is usually started at a dosage of 20 mg daily for depression in adults. 

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 differences in approved uses and dosage forms. 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, while Prozac comes as an oral capsule. 

Is Zoloft vs. Prozac better?

Zoloft and Prozac are both comparable in efficacy. Most studies have shown no significant differences in efficacy with either medication. However, they may have different side-effect profiles. Some studies suggest that Zoloft may be more tolerable than Prozac. Still, SSRIs may work differently for everyone. It’s best to consult a mental healthcare provider for the most appropriate treatment option depending on overall symptoms and the condition being treated.

How long do I need to take Zoloft and Prozac?

There are no strict guidelines for how long antidepressants like Zoloft or Prozac should be taken. Most healthcare providers recommend staying on antidepressants for around six to eight weeks to experience the full therapeutic effects of the medication. In most cases, treatment with antidepressants is a long-term endeavor. However, suppose you feel you no longer need to take an antidepressant or have other reasons for stopping treatment. In that case, you should discuss your options and discontinue the antidepressant with the help of a healthcare provider. 

How long does Zoloft and Prozac take to work?

With Zoloft or Prozac, as with other SSRI antidepressants, symptoms may begin to improve within one to two weeks of treatment. However, in many cases, it can take around six to eight weeks to experience the full therapeutic effects of these medications. If symptoms haven’t improved by eight weeks of treatment, you may want to discuss adjusting the dosage or switching medications with a healthcare provider. 

Can I use Zoloft vs. Prozac while pregnant?

Zoloft and Prozac may be used during pregnancy if the benefits outweigh the potential risks. Some research suggests that the use of SSRIs during late pregnancy may increase the risk of pulmonary hypertension, among other problems, in an infant. Some studies have linked Prozac and other SSRIs, except Zoloft, to heart and skull defects. Consult your healthcare provider if you are pregnant or breastfeeding before starting or continuing treatment with an SSRI.

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 may increase the risk of certain side effects, such as dizziness and drowsiness. 

Which SSRI has the least side effects?

As part of the same class of drugs, Zoloft and Prozac may cause similar side effects. However, Zoloft may cause more digestive and sexual side effects, while Prozac may cause more headaches. Side effects from SSRIs are often mild and resolve over time as the body gets used to the drug. 

Is Prozac good for anxiety?

Prozac is FDA-approved to treat panic disorder, which is a type of anxiety disorder. However, Prozac may also be prescribed off-label for general and social anxiety disorders. It may also be useful for people with both depression and anxiety.