Paxil vs Zoloft: What’s the Difference?

Published on: 18 Oct 2023
Clinically Reviewed by Bisma Anwar, LMHC
Paxil vs. Zoloft

Paxil (Paroxetine) and Zoloft (Sertraline) are medications popular for treating mental health conditions like depression and various mood disorders. Both are in a class of drugs known as selective serotonin reuptake inhibitors (SSRIs), which are commonly used antidepressants. 

Trying to choose between using Paxil and Zoloft can leave many people feeling confused. It’s important to remember that selective serotonin reuptake inhibitor drugs can work differently for everyone — things like body chemistry and individual needs come into play when deciding which medication is most suitable. 

To make an informed decision about your treatment plan, it’s critical to understand the difference between Paxil and Zoloft. Before obtaining a Zoloft online prescription or getting a prescription for Paxil, you must look at their uses, side effects, and how they work. While your doctor should help you decide which drug will be most effective, you can continue reading to learn whether Paxil or Zoloft might be right for you.

Conditions They TreatMajor depressive disorder
Panic disorder
Generalized anxiety disorder
Major depressive disorder
Panic disorder
Some anxiety disorders
Common Side EffectsNausea
Sexual dysfunction
Risk of bleeding
Weight gain  
Nausea or vomiting
Dry mouth
Dizziness or lightheadedness
Sexual side effects
Weight change
Key ConsiderationsDrug interactions may occur

Increased risk of suicidal thoughts in some people

Available in brand name or generic
Can interact with other drugs

Safe at therapeutic levels; however, may exacerbate existing heart issues

Available in brand name or generic

Differences Between Paxil vs. Zoloft

To compare Paxil and Zoloft, it’s necessary to assess the differences between these drugs. Both SSRI antidepressant medications affect neurotransmitters in the brain to help maintain balance. Still, they work slightly differently, and which is best will depend on several factors. 

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Conditions they treat

While both drugs are antidepressants and treat some of the same conditions, there are also  some differences in others Paxil versus Zoloft can treat.

Paxil is FDA-approved to address symptoms of: 

Paxil off-label uses include:

Zoloft is approved by the FDA to treat: 

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

Zoloft off-label uses include:

  • Autism
  • Disordered eating
  • Generalized anxiety disorder (GAD)
  • Personality disorders

Note that off-label uses for any drug have been seen as effective, but they’re not FDA approved. 

Dosage amount

Dosage can vary between Paxil and Zoloft, and it’s important to take either drug exactly as prescribed. 

Paxil is available in either immediate or controlled release forms:

  • Immediate-release — Start with 10 – 20 mg, increased by 10 mg weekly if needed, only as advised by a doctor; maximum of 50 mg daily.  
  • Controlled release: Start with 12.5 – 25 mg, increased by 12.5 mg weekly if needed, only as advised by a doctor; maximum of 62.5 mg per day. 

Zoloft is available in the following dosages and forms:

  • Tablets — 25, 50, or 100 mgs
  • Capsule — 150 – 200 mg
  • Liquid — 20 mg/mL

Side effects

When we compare Paxil and Zoloft, we need to look at each drug’s side effects. While some reactions can be the same, the drugs can affect everyone differently.

Common side effects of Paxil:

  • Nausea
  • Weakness
  • Drowsiness 
  • Sexual dysfunction
  • Risk of bleeding
  • Weight gain  

Common side effects of Zoloft:

  • Nausea or vomiting
  • Diarrhea
  • Dry mouth
  • Headache
  • Dizziness or lightheadedness
  • Sexual side effects
  • Weight change

Does Paxil have less side effects than Zoloft?

Before deciding if Zoloft is better than Paxil, or vice versa, remember that Individual responses can vary. Factors like health conditions, age, and concurrent use of other medications can all impact how a drug affects someone. 

Some research suggests Zoloft may be tolerated better in certain people, but knowing which drug is best for you will ultimately be decided by you and your doctor.

Does Paxil or Zoloft make you gain weight?

  • Paxil: Not everyone will experience weight gain on Paxil, but it’s important to note that about 1% of people in clinical trials did see weight gain related to taking the drug. Some research suggests that weight gain is more likely with Paxil than with other SSRIs.  
  • Zoloft: Significant research shows that Zoloft weight gain is temporary and moderate. While it can be expected for people on antidepressants to see weight gain as a side effect, studies show that Zoloft may have less risk of causing significant weight gain than other antidepressants. 

Similarities Between Paxil & Zoloft

Paxil and Zoloft share several similarities in how they work, the conditions they treat, dosage, forms, and how they are administered. 

Similarities include both medications:

  • Are both in the SSRI class of drugs
  • Block reabsorption of serotonin into neurons
  • Increase the availability of serotonin levels in the brain to enhance mood regulation
  • Are used to treat major depressive disorder, obsessive-compulsive disorder, and panic disorder

How they work

SSRIs like Paxil and Zoloft work by altering levels of the neurotransmitter serotonin in the brain. Serotonin carries signals in the brain from nerve cell to nerve cell. It’s believed to impact emotions, mood, and sleep positively. SSRIs stop serotonin from being transported and reused, keeping higher serotonin levels available to improve symptoms of certain mental health conditions like depression, anxiety, and mood disorders. 

Anxiety and depression treatment

Paxil and Zoloft for anxiety work in the same way, but efficacy can differ for individual people. 

Paxil treats various forms of anxiety, including panic attacks, social anxiety, generalized anxiety disorder, and post-traumatic stress disorder. It can relieve irritability and restlessness, which anxiety often causes. Zoloft is also known to be effective in treating a variety of anxiety disorders, including obsessive-compulsive disorder. Research shows it can effectively treat extreme forms of social phobia.

Paxil and Zoloft can both regulate mood and treat some forms of depression. 

“Zoloft and Paxil are SSRIs working on serotonin, a major neurotransmitter. They work by increasing leads to resolving symptoms. These treat depression and anxiety, and the selection between Zoloft and Paxil is based on the severity of symptoms. The dose needed is a combination of meds, tolerability, and side effects. For severe anxiety disorders, PTSD, and OCD, higher doses are needed. Zoloft used in much higher doses is tolerated better.”

Talkspace psychiatrist Dr. Muhammad Munir

Determine if Paxil or Zoloft Is Right for You with Talkspace

Finding the right SSRI antidepressant medication to treat your mental health effectively can be overwhelming. Understanding how each drug functions, its potential side effects, and suitability for a specific condition takes time and patience. 

Online psychiatrists at Talkspace can help guide you through the process. Connect with licensed and experienced therapists who specialize in mental healthcare. Together, you can compare Paxil and Zoloft to figure out if one might be better for you and your circumstances.

Contact Talkspace today to learn more about the difference between Paxil and Zoloft treatment options.


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  2. Liebowitz MR, DeMartinis NA, Weihs K, et al. Efficacy of sertraline in severe generalized social anxiety disorder. The Journal of Clinical Psychiatry. 2003;64(7):785-792. doi:10.4088/jcp.v64n0708. Accessed August 20, 2023.
  3. Nevels RM, Gontkovsky ST, Williams BE. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacol Bull. 2016;46(1):77-104. Accessed August 20, 2023.
  4.  PAXIL- paroxetine hydrochloride tablet, film coated. U.S. Food and Drug Administration. Accessed August 20, 2023.  
  5. Deshmukh, MD R, Franco, MD K. Managing weight gain as a side effect of antidepressant therapy. Cleveland Clinic Journal of Medicine. 2003;70(7). Accessed August 20, 2023.
  6. Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: Population based cohort study. BMJ. Published online 2018. doi:10.1136/bmj.k1951. Accessed August 20, 2023.

Talkspace articles are written by experienced mental health-wellness contributors; they are grounded in scientific research and evidence-based practices. Articles are extensively reviewed by our team of clinical experts (therapists and psychiatrists of various specialties) to ensure content is accurate and on par with current industry standards.

Our goal at Talkspace is to provide the most up-to-date, valuable, and objective information on mental health-related topics in order to help readers make informed decisions.

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