Paxil vs Zoloft: Which is Right for Me?

By Latifa deGraft-Johnson, MD
Medically reviewed checkmarkMedically reviewed
March 16, 2022

Paxil and Zoloft are two antidepressants that may be prescribed to treat depression or other mood disorders.

Even though they both have the same treatment goal, there are some key differences between these two drugs.

In this article, we’ll explore how Paxil and Zoloft are similar, the ways they are different, their uses, and their side effects.

What is Paxil?

Paxil (paroxetine HCl) is a selective serotonin reuptake inhibitor (SSRI) that is available by prescription only.

It is approved by the Food and Drug Administration (FDA) to treat conditions such as depression, anxiety, post-traumatic stress disorder, and others.

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Paxil uses

Paxil is FDA-approved as a treatment for the following:

How Paxil works

As a drug in the SSRI class, Paxil helps to balance neurotransmitters in the brain.

Specifically, it helps decrease the reuptake of serotonin, leading to more balanced levels and supporting better mood, feelings of calm, and overall perception of well-being.

What is Zoloft?

Zoloft (sertraline HCl) is an FDA-approved medication for treating depression and other mood disorders.

Like Paxil, it is an SSRI.

Zoloft uses

Zoloft is FDA-approved as a treatment for the following:

  • Major depressive disorder (MDD)
  • Obsessive-compulsive disorder (OCD)
  • Panic disorder
  • Post-traumatic stress disorder (PTSD)
  • Social anxiety disorder
  • Premenstrual dysphoric disorder (PMDD)

How Zoloft works

Zoloft is another SSRI, like Paxil, and blocks the rapid clearance of serotonin from the brain.

This has mood-stabilizing effects and can reduce depression, anxiety, and other mood-related symptoms.

How Are They Similar?

Paxil and Zoloft have many similarities.

They both:

  • Are SSRI antidepressants
  • Support balanced serotonin levels in the brain
  • Have similar side effects
  • Are taken once daily
  • Are FDA-approved for treating depression, OCD, PTSD, and other mood-related disorders
  • Are both available as liquid or tablet form (although Paxil is also available in a controlled-release form)

Drug class

Paxil and Zoloft are selective serotonin reuptake inhibitors, also known as SSRIs.

They are a common class of antidepressants that help stabilize the number of neurotransmitters available to the brain.

They are called “selective” because they affect serotonin and not other neurotransmitters, like dopamine or norepinephrine.

Effectiveness at treating depression

In clinical trials, Paxil was found to be significantly more effective at treating depression in patients 18 and older when compared to placebo.

It led to improvements in depressed mood, sleep disturbance, and anxiety.

Patients who took Paxil had significantly lower relapse rates when compared to placebo.

It was found to be equally as effective for people of all genders.

Zoloft’s effectiveness at treating depression has also been validated by clinical trials.

It is often favored in comparison to other types.

Studies have found Zoloft to be effective for many types of depression and mood disorders, including postpartum depression.

There were no sex differences noted in how patients responded to treatment.

Both Paxil and Zoloft are shown by research to be effective pharmaceutical interventions for depression, anxiety, and other mood disorders.

How they work in comparison to each other depends largely on a person’s genetic makeup, health conditions, and other prescriptions that they take.

How Are They Different?

Paxil and Zoloft have many similarities, but they are not the same drug and are not used interchangeably.

Conditions treated

Paxil and Zoloft are both approved by the Food and Drug Administration (FDA) for treatment of the following:

  • Major depressive disorder
  • Obsessive-compulsive disorder (OCD)
  • Social anxiety disorder
  • Post-traumatic stress disorder (PTSD)
  • Panic disorder
  • Premenstrual dysphoric disorder (PMDD)

Paxil is also FDA-approved for treating generalized anxiety disorder (GAD) and vasomotor symptoms associated with menopause.

Zoloft is only approved for use in children and adolescents for the treatment of OCD, while Paxil is not FDA-approved for use in children.

Both drugs may be used for off-label purposes at the discretion of health care providers.

Off-label uses of Paxil may include:

  • OCD in children and adolescents
  • Social anxiety disorder in children and adolescents
  • Separation anxiety
  • Dysthymia
  • Body dysmorphic disorder
  • Postpartum depression
  • Premature ejaculation
  • Malignancy related pruritus that does not respond to standard treatment

Off-label uses of Zoloft may include:

  • Binge eating disorder
  • Body dysmorphic disorder
  • Bulimia nervosa
  • Generalized anxiety disorder (GAD)
  • Premature ejaculation

Standard dosage

Paxil and Zoloft have different dosages.

They are different drugs, so the dosages are not directly comparable.

Paxil is available in immediate-release and controlled-release formulations.

It is available as tablets or in liquid form. It may be taken with or without food.

  • Immediate-release: Doses start at 20 mg and increase in 10 mg weekly increments until a maximum of 50 mg per day is reached. Geriatric adults start at 10 mg with a max dose of 40 mg per day.
  • Controlled release: Doses start at 25 mg and increase in 12.5 mg weekly increments with a maximum of 62.5 mg per day. Geriatric adults start at 12.5 mg with a max dose of 25 mg per day.

Zoloft is available in oral tablets, capsules, and liquid solution. Absorption is best when taken with food.

  • Oral tablets: Available in 25 mg, 50 mg, or 100 mg
  • Oral capsules: Available in 150 mg and 200 mg
  • Liquid solution: Available as 20 mg/mL

Dosages for depression start at 50 mg per day for adults and are increased in 50 mg per day increments in weekly intervals as needed or until a maximum dosage of 200 mg per day is reached.

Potential side effects

Paxil and Zoloft have some similar side effects.

Common side effects of Paxil may include:

  • Nausea
  • Sleepiness
  • Weakness
  • Dizziness
  • Feeling anxious
  • Insomnia
  • Sexual problems
  • Sweating
  • Shaking
  • Loss of appetite
  • Dry mouth
  • Constipation
  • Yawning

Side effects of Zoloft may include:

Paxil Precautions

Like other antidepressants, Paxil comes with a black box warning.

If signs of increased agitation, worsening anxiety, panic attacks, extreme irritability, impulsiveness, or manic behavior occur, let your healthcare provider know.

If you or someone you love has thoughts of self-harm or experiences suicidal ideation, get medical help immediately.

This risk is most increased in children, adolescents and young adults, but can affect anyone at any age. 

The risks and benefits should be weighed with your healthcare provider.

Paxil is not safe for people with certain health conditions or who take specific medications.

If any of the following are applicable to you, Paxil may not be an appropriate prescription choice.

  • Takes MAOIs or has within the past 14 days
  • Takes thioridazine
  • Takes pimozide
  • Is sensitive to any ingredients in Paxil

Zoloft Precautions

Zoloft carries a black box warning, as well.

If you notice the following warning signs, let a healthcare provider know right away:

  • Agitation, aggression, or hostility
  • Increased or worsening anxiety
  • Panic attacks
  • Irritability
  • Insomnia
  • Impulsiveness
  • Unusual changes in behavior
  • Suicidal thoughts or discussion (this risk is greater in children, adolescents and young adults, but can affect any age.)
  • Restlessness
  • Manic behavior

Zoloft is contraindicated for people with certain health conditions or who take specific medications.

If any of the following apply, your doctor will not prescribe Zoloft:

  • Takes MAOIs or has within the past 14 days
  • Takes pimozide
  • Is sensitive to sertraline or any ingredients in Zoloft
  • Takes disulfiram (for liquid Zoloft only)
  • Liver disease or cirrhosis (Child-Pugh classes A, B, or C impairment)

Always let medical providers know the other prescriptions, OTC drugs, herbs, or supplements that you take so that you can avoid potentially serious side effects and interactions, like gastrointestinal bleeding, heart arrhythmias, serotonin syndrome, all of which can be life-threatening.

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When to See a Doctor for Depression

You should see your doctor if you are having any signs of depression, including persistent feelings of sadness, lack of motivation, or trouble caring about things that used to excite you.

Your doctor may not always recommend an antidepressant, but they will be able to help you find a care plan that works for you and supports your quality of life.

In addition, your healthcare provider will be able to discuss risks and benefits of treatment plan options that are available to you.

Frequently Asked Questions

Is Zoloft or Paxil better?
Zoloft and Paxil are in the same drug class but work slightly differently. Whether or not one works better for you depends on your individual response to the drug, your health conditions, your age, and other medications you may take.
Does Paxil have more side effects than Zoloft?
Paxil and Zoloft have a similar number of common side effects. You may or may not experience side effects while taking Paxil or Zoloft. How your body responds to one drug, including what side effects you experience, will be different from someone else. Zoloft has a greater risk of interactions with other medications, including over the counter medications that you may be taking. Please discuss with your healthcare provider to determine your best treatment options.
Is Paxil the best medication for anxiety?
Paxil is FDA-approved for the treatment of anxiety. Zoloft is FDA-approved for the treatment of panic disorder, social anxiety disorder, but has an off-label use for generalized anxiety disorder. There are many anxiolytic drugs, and your doctor will recommend the one that best meets your age, symptoms, and other circumstances.
Is Paxil the strongest SSRI?
Paroxetine (Paxil) is the most potent SSRI available, meaning that it has the strongest effect on preventing the reuptake of serotonin. Even at a lower dose, it may have a stronger effect on neurotransmitters than other SSRI drugs.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Latifa deGraft-Johnson, MD

Dr. Latifa deGraft-Johnson is a board-certified family medicine physician with 20 years of experience. She received her bachelor's degree from St. Louis University, her medical degree from Ross University, and completed her family medicine residency at the University of Florida. Her passion is in preventative medicine and empowering her patients with knowledge.