Paxil vs. Zoloft: 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

Paxil (paroxetine) and Zoloft (sertraline) are SSRIs (selective serotonin reuptake inhibitors) that are indicated for the treatment of depression and other mental health conditions. An SSRI works by increasing serotonin levels in the brain, which helps improve symptoms. Both prescription drugs are approved by the Food and Drug Administration (FDA). Examples of other medications in the SSRI class are Prozac (fluoxetine), Celexa (citalopram), and Lexapro (escitalopram). Although Paxil and Zoloft are similar, they have some differences as well.

What are the main differences between Paxil and Zoloft?

Paxil and Zoloft are SSRI (selective serotonin reuptake inhibitor) medications. Both drugs are available in brand and generic. The generic name for Paxil is paroxetine, and the generic name for Zoloft is sertraline. Although dosing varies, a typical dose for Paxil is 20 mg daily, and a typical dose for Zoloft is 50 mg daily. Paxil is available in tablet form, as well as extended-release tablets, and suspension. Zoloft is available in tablet form and as a solution.

Conditions treated by Paxil and Zoloft

Paxil and Zoloft are both indicated for major depressive disorder (depression), obsessive-compulsive disorder, panic disorder, social anxiety disorder, posttraumatic stress disorder, and premenstrual dysphoric disorder. Paxil is also approved to treat generalized anxiety disorder. Zoloft is not FDA-approved for generalized anxiety disorder, but some healthcare providers prescribe it off-label for this use. 

Is Paxil or Zoloft more effective?

In a randomized, double-blind study comparing the two drugs for the treatment of panic disorder, Paxil and Zoloft were found to be equally effective; however, Zoloft was slightly better tolerated, and patients did better when discontinuing the drug. 

In another randomized, double-blind study of Paxil and Zoloft for 24 weeks, both drugs were similarly effective in improving the quality of life scores in patients with major depressive disorder. Paxil and Zoloft were also well-tolerated, with Zoloft patients having fewer side effects. 

Another study looked at Paxil and Zoloft, as well as Prozac, in patients with major depression and high levels of anxiety (anxious depression) and found all three drugs to be similarly effective and well-tolerated.

The most effective medication for you should only be determined by your healthcare provider, who can take into account your medical condition(s), history, and other medications you are taking that could interact with Paxil or Zoloft.

Coverage and cost comparison of Paxil vs. Zoloft

Generic Paxil (paroxetine) and generic Zoloft (sertraline) are usually covered under most insurance as well as Medicare prescription plans. Without insurance, a 30-day supply of 20 mg name-brand Paxil will cost around $327, and a 30-day supply of 50 mg brand-name Zoloft costs about $493. Insurance and Medicare copays vary by plan. Choosing the generic versions of these drugs will save a significant amount of money. You can pay $4-$16 for paroxetine and about $7-17 for sertraline. 

Common side effects of Paxil vs. Zoloft

The most common adverse effects of Paxil are nausea, drowsiness, headache, dry mouth, and weakness. The most common adverse effects of Zoloft are nausea, dry mouth, diarrhea, and insomnia. Both drugs have a similar list of side effects, as seen below, with varying percentages of patients experiencing these side effects. 

Consult your healthcare provider for a complete list of side effects.

Source: DailyMed (Paxil), DailyMed (Zoloft)

Drug interactions of Paxil vs. Zoloft

MAO inhibitors (monoamine oxidase inhibitor antidepressants) in combination with Paxil or Zoloft can be very dangerous and potentially fatal. The use of MAO inhibitors should be separated from SSRIs by at least 14 days. 

Using Paxil or Zoloft in combination with other drugs that increase serotonin, as well as with other SSRIs, SNRIs, or tricyclic antidepressants, can increase the risk of serotonin syndrome. Aspirin and other NSAIDs should not be used with Paxil or Zoloft as they can increase the risk of bleeding. 

Many other drugs may interact with Paxil or Zoloft. Consult your healthcare provider for a complete list of drug interactions.

Warnings of Paxil vs. Zoloft

All antidepressants, including Paxil and Zoloft, come with a black box warning, which is the strongest warning required by the FDA (Food and Drug Administration). Antidepressants increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults. Depression and other psychological disorders also increase the risk of suicide. 

Patients of any age who take antidepressants should be closely monitored for signs of changes in behavior, and suicidality, especially during the first few months of treatment and if any changes in dose occur. Families and caregivers should also monitor the patient, and notify the prescriber of any issues. 

Additionally, there are other warnings that come with both Paxil and Zoloft:

• Before treatment begins, the patient should be screened for bipolar disorder. Patients with bipolar disorder may initially have a depressive episode. Paxil or Zoloft will not work for bipolar disorder, and may actually worsen bipolar disorder. 
• The development of a serious, potentially life-threatening condition called serotonin syndrome has occurred with SSRI antidepressants. Symptoms of serotonin syndrome may include agitation, hallucinations, rapid heartbeat, dizziness, sweating, flushing, fluctuating blood pressure, tremor, incoordination, seizures, nausea, vomiting, or diarrhea. 
• The risk for serotonin syndrome increases when other drugs are taken together with Paxil or Zoloft that also increase serotonin, such as triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamines, and St. John’s Wort.
• The combination of Paxil or Zoloft with an MAOI (monoamine oxidase inhibitor) is dangerous and is contraindicated. Examples of MAOI include Eldepryl (selegiline), Azilect (rasagiline), Nardil (phenelzine), and Parnate (tranylcypromine). There should be a separation of 14 days between using an MAOI and an SSRI.
• Paxil or Zoloft should not be used with Mellaril (thioridazine); the combination could cause ventricular arrhythmia and lead to sudden death.
• Use with caution in patients that have seizures.
• When Paxil or Zoloft is discontinued, the medication should be gradually tapered and not stopped abruptly, to avoid withdrawal symptoms.
• Hyponatremia (low sodium in the blood) may occur, due to SIADH (syndrome of inappropriate antidiuretic hormone secretion). Patients who take diuretics or those who are dehydrated are at higher risk. 
• SSRI medications may increase the risk of bleeding. They should not generally be used in combination with aspirin or other NSAIDs such as ibuprofen or naproxen, or blood thinners such as Coumadin (warfarin). 
• Monitor for risk of bone fracture.
• Paxil or Zoloft may cause pupillary dilation and may trigger an angle-closure attack in patients with anatomically narrow angles.

Consult your healthcare provider for medical advice if you are pregnant, planning to become pregnant, or breastfeeding. 

Frequently asked questions about Paxil vs. Zoloft

What is Paxil?

Paxil (also known by its generic name paroxetine) is an FDA-approved medication in the SSRI drug class, that is used to treat major depressive disorder, OCD, and anxiety disorders. 

What is Zoloft?

Zoloft (sertraline) is an FDA-approved medication in the SSRI drug class, which is used to treat major depressive disorder as well as various anxiety disorders. 

Are Paxil and Zoloft the same?

Paxil and Zoloft are similar, but not the same. While they are both SSRIs and work in the same way, they have some differences, as described above. Examples of other SSRI drugs include Prozac (fluoxetine), Celexa (citalopram), Lexapro (escitalopram), Viibryd (vilazodone), and Luvox (fluvoxamine). 

Is Paxil or Zoloft better? / Is sertraline better than paroxetine?

Both drugs are well-tolerated and can be very effective in the treatment of depression as well as anxiety disorders. Ask your doctor if one of these drugs may be right for you.

Can I use Paxil or Zoloft while pregnant?

There are various possible risks to consider regarding antidepressant use during pregnancy. Either drug can cause complications if used in the third trimester of pregnancy. Paxil can also cause harm to the unborn baby if used in the first trimester. Ask your healthcare provider for medical advice. If you are already taking Paxil or Zoloft and find out that you are pregnant, contact your healthcare provider for medical advice. 

Can I use Paxil or Zoloft with alcohol?

The manufacturer’s information for both drugs indicates that patients should not drink alcohol while taking Paxil or Zoloft. 

Are Zoloft and sertraline the same thing?

Yes. Zoloft is the brand name of the medication. Sertraline is the generic name. Most patients take sertraline, the generic. 

Which antidepressants have the least side effects?

All antidepressants come with a list of warnings and side effects, as outlined above. However, because everyone is different, many people react differently to different antidepressants. Sometimes it takes a bit of trial and error to find the one that works best for you, with the least side effects. 

Is Paxil a good antidepressant?

All of the SSRI antidepressants have gone through extensive clinical trials to establish safety and efficacy. Consult your healthcare provider to see if Paxil is right for you.