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Key takeaways
Zoloft and Prozac are both SSRIs used to treat depression and other mental health conditions, but they differ in approved uses, forms, and dosages.
Common side effects of both drugs include nausea and indigestion, but Zoloft may have a slightly better side effect profile according to some studies.
Zoloft and Prozac have similar effectiveness in treating depression and anxiety, with no significant differences in symptom improvement in most studies.
Both medications are available in generic form and are typically covered by insurance, but consulting a healthcare professional is crucial for determining the most suitable treatment.
If you are living with depression, your healthcare provider may recommend an SSRI medication to help manage symptoms. SSRIs, or selective serotonin reuptake inhibitors, increase serotonin levels in the brain, which may help improve mood and feelings of well-being.
Zoloft (sertraline) and Prozac (fluoxetine) are two SSRIs that can treat depression in addition to other mental health conditions, such as panic disorder and obsessive-compulsive disorder (OCD). Although these antidepressants work similarly, Zoloft and Prozac have some important differences.
| Zoloft | Prozac | |
| Drug class | SSRI | SSRI |
| Brand/generic status | Brand and generic version available | Brand and generic version available |
| What is the generic name? | Sertraline | Fluoxetine |
| What form(s) does the drug come in? | Oral tablet
Oral solution |
Oral capsule |
| What is the standard dosage? | 50 to 200 mg per day | 20 to 60 mg per day |
| How long is the typical treatment? | Short- or long-term | Short- or long-term |
| Who typically uses the medication? | Adults and children, depending on the condition being treated | Adults and children, depending on the condition being treated |
What are the main differences between Zoloft vs. Prozac?
Zoloft is the brand name for sertraline hydrochloride. Many people may be familiar with the brand-name version manufactured by Viatris, a Pfizer company. However, a generic version of Zoloft is available. Zoloft comes as 25 mg, 50 mg, and 100 mg oral tablets and as a 20 mg/mL oral solution. It is usually taken once daily.
Prozac, which Eli Lilly manufactures, is the brand name for fluoxetine. A generic version of Prozac is also widely available. Prozac is usually prescribed as a 10 mg, 20 mg, or 40 mg oral capsule taken daily. It was previously available as a delayed-release oral capsule taken weekly. However, Prozac’s delayed-release capsules have been discontinued in the United States.
Conditions treated by Zoloft vs. Prozac
Zoloft is commonly prescribed for the treatment of major depressive disorder, OCD, and panic disorder. However, it is also approved by the U.S. Food and Drug Administration (FDA) to treat social anxiety disorder, premenstrual dysphoric disorder (PMDD), and post-traumatic stress disorder (PTSD). In some cases, Zoloft may be used off-label for bipolar depression and an eating disorder called bulimia nervosa.
Like Zoloft, Prozac may be prescribed to treat major depressive disorder, OCD, and panic disorder. In addition, Prozac is FDA-approved to treat an eating disorder called bulimia nervosa. It is also approved for depressive episodes of bipolar I disorder when used with olanzapine. The active ingredient of Prozac may be used to treat PMDD, but it’s marketed under a different brand 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 |
| OCD | Yes | Yes |
| Panic disorder | Yes | Yes |
| PTSD | Yes | Off-label |
| Social anxiety disorder | Yes | Off-label |
| PMDD | Yes | Yes |
| Bulimia nervosa | Off-label | Yes |
| Generalized anxiety disorder | Off-label | Off-label |
| 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. Medication dosage forms are an important aspect of treatment, as some people may have certain preferences. For example, someone with trouble swallowing capsules may prefer a liquid or oral solution.
Dosages vary depending on the condition being treated, the person’s age, and other factors. Always consult a healthcare provider for the most appropriate dosage plan.
| 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: 25 or 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 |
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.
Prozac may cause insomnia if taken at bedtime, especially when treatment is first started. Therefore, healthcare providers typically recommend taking Prozac in the morning. On the other hand, Zoloft may be taken in the morning or evening.
Dosages in specific populations
A lower dosage of Zoloft and Prozac may be recommended in older adults 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 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 individuals 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
Insurance plans usually cover Zoloft. The prices will often be quite reasonable since it is available as a generic. However, the average retail cost of a 30-day supply of brand-name Zoloft is around $500. 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 $700. 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 | Varies | Varies |
| SingleCare cost | $6 | $ |
Common side effects of Zoloft vs. Prozac
Since Zoloft and Prozac are in the same class of medications, they both have similar side effects. Side effects from antidepressant medications 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% |
Frequency is not based on data from a head-to-head trial. This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more.
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. These side effects may include serotonin syndrome, allergic reactions, glaucoma, and an increased risk of bleeding. In addition, these medications may cause suicidal thoughts or behaviors, especially in children and adolescents.
If serious side effects occur, it may be necessary to seek immediate medical attention. The risk of serious side effects is usually increased in people taking other prescription drugs or people with pre-existing medical conditions.
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 |
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. The dosage should be tapered slowly with proper medical guidance when discontinuing these medications.
Zoloft and Prozac are in Pregnancy Category C and may cause harm to an unborn baby. They should only be used if the benefits outweigh the potential pregnancy risks. Consult a healthcare provider if you are pregnant or breastfeeding before taking an SSRI like Zoloft or Prozac.
Frequently asked questions about Zoloft vs. Prozac
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. For example, although both drugs are approved for major depression, OCD, and panic disorder, Zoloft is also approved for PTSD and social anxiety disorder. In contrast, Prozac is also approved for bulimia and depressive episodes of bipolar disorder. Zoloft is available as an oral tablet and liquid solution, while Prozac is available 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. Healthcare providers may recommend staying on antidepressants for at least 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 do 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 several weeks to experience the full therapeutic effects of these medications. If symptoms haven’t improved by six to 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 high blood pressure in the lungs in an infant. Some studies have linked SSRIs to skull defects in babies, especially when taken during the first trimester. 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 prescription 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.
Sources
- Zoloft highlights of prescribing information, U.S. Food and Drug Administration (2023)
- Prozac highlights of prescribing information, U.S. Food and Drug Administration (2023)
- Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression, International Clinical Psychopharmacology (1993)
- Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression, Journal of Affective Disorders (2000)
- What are the real risks of antidepressants?, Harvard Health (2021)
- A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients, European Psychiatry (1999)
- The FDA “Black Box warning on antidepressant suicide risk in young adults: More harm than benefits?, Frontiers in Psychiatry (2019)
- Going off antidepressants, Harvard Health (2022)
- Depression: Learn more – how effective are antidepressants?, InformedHealth.org (2006)
- Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries, The BMJ (2012)
- Depression and antidepressants during pregnancy: Craniofacial defects due to stem/Progenitor cell deregulation mediated by serotonin, Frontiers in Cell and Developmental Biology (2021)