Paxil Vs Zoloft | A Clinician’s Detailed Review
Written By Kobi Nathan, Pharm.D., M.Ed., CDP, BCGP, AGSF
Sleep Disorders
January 11, 2024

Paxil (generic name paroxetine) and Zoloft (generic name sertraline) are two medications belonging to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

Although they are similar in how they work in the brain to regulate mood, there are distinct differences between them.

In this article, I will review the benefits, side effects, similarities, and differences between Paxil vs Zoloft so you can decide which of the two agents may be best for you.

Key Takeaways

  • Paxil and Zoloft are both SSRIs commonly used to treat depression and anxiety, among other mental health conditions.
  • Both medications work by increasing levels of serotonin in the brain to improve mood and reduce anxiety.
  • Side effects of both medications range from mild to severe and may include drowsiness, dizziness, nausea, and sexual dysfunction.
  • Sertraline is better for older adults due to its tolerability, lower side effect profile, and effectiveness.
  • Older adults should not use Paxil, especially if they have dementia.

Paxil Vs Zoloft – Uses

Paxil Uses

Paxil is approved by the Food and Drug Administration (FDA) for treating the following conditions:

  • Major depressive disorder (MDD)
  • Obsessive-compulsive disorder (OCD)
  • Panic disorder (PD)
  • Social anxiety disorder (SAD)
  • Generalized anxiety disorder (GAD)
  • Posttraumatic stress disorder (PTSD)

Zoloft uses

Zoloft is FDA-approved for treating the following conditions:

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

If you want to learn more about the mental health conditions I have listed above, read my detailed article Anxiety vs PTSD.

Additionally, the SSRIs mentioned in this article are different from other medications also commonly prescribed to treat anxiety and depression, such as bupropion and hydroxyzine.

Bupropion works well when paired with an SSRI to manage depression but not anxiety.

Importantly, bupropion has positive sexual side effects which help counter the negative side effects seen with SSRI use.

To understand how increased serotonin levels can cause sexual dysfunction, watch this short informative video:

Similarities and Differences Between Paxil and Zoloft

Are Zoloft and Paxil Similar?

In several ways, paroxetine and sertraline are similar.

As I mentioned earlier, both drugs belong to the SSRI antidepressant class.

They work specifically to increase levels of the brain chemical serotonin, a neurotransmitter vital to regulating mood, appetite, sleep, fear, and sexual behavior, among other things.

Additionally, Paxil is available in both brand and generic formulations, as is sertraline.

Both are approved to treat the different forms of anxiety as well as depression.

 How are Paxil and Zoloft Different?

The table below highlights some of the key differences when comparing Paxil vs Zoloft:

Key Differences Between Paxil And Zoloft

Key Factors PaxilZoloft
Generic name?paroxetinesertraline
Dosage FormImmediate-release tablets
Extended-release tablets
Oral suspension
Tablets (once daily)
Oral solution
Typical dose range10-60 mg daily25-200 mg daily
Who is approved to take?Adults
Children treated for OCD

Dosages and Dosage Forms

To determine the appropriate dosages and dosage forms of Paxil and Zoloft, it’s important to consult with a healthcare provider.

Dosing for both medications typically starts low and gradually increases based on individual response and tolerance (Start low, go slow, go all the way).

Your healthcare provider will consider factors such as your condition’s severity, age, and any other medications you may be taking.

Older adults are especially vulnerable to drug adverse effects if medication initiation, dose escalation, and monitoring for efficacy and safety are not given the attention they deserve.

To understand how serious this issue is, read my article on polypharmacy.

Both Paxil and Zoloft are available in various dosage forms, including tablets, extended-release tablets, and suspension.

The choice of dosage form will depend on your specific needs and preferences.

It’s important to note that common side effects of both medications should be considered when determining the appropriate dosage and form.

Your healthcare provider will help you understand and manage any potential side effects related to the dosage and form of Paxil and Zoloft.

It is crucial to follow their guidance and communicate any concerns or changes in your symptoms.

Remember, only a healthcare provider can provide personalized and contextually relevant recommendations regarding the dosages and dosage forms of Zoloft.

Common side effects of Paxil and Zoloft

Both Paxil and Zoloft can cause the following common side effects:

As you can see above, you may experience drowsiness or insomnia.

The reason why this may seem paradoxical is that everyone responds to medications differently.

This can be seen especially with sertraline.

So, depending on how you respond to it, you may need to take your medication either in the morning if you experience insomnia with it or you may need to take it at bedtime if you experience drowsiness.

I write all about this in my article, Best time to take Zoloft.

Serious side effects of Paxil

As you begin taking paroxetine, you may experience side effects that are severe.

These include:

  • Confusion
  • Breathing difficulty
  • Seizures
  • Tremors
  • Racing or irregular heartbeat
  • Skin rash

Important clinical consideration:

Many providers hardly understand this, but I need to make an important comment about Paxil here.

In my clinical experience, Paxil is the least likely antidepressant that I will recommend for anyone.

It is especially dangerous for older adults.

There are 3 major reasons why I say this:

  1. You can experience severe withdrawal symptoms from missing even ONE dose of Paxil due to its short half-life! (Yes, I have seen this in my patients!)
  2. It interacts with many medications.
  3. It has high anticholinergic burden, which worsens dementia.


Serious side effects of Zoloft

Severe side effects of sertraline include:

  • Aggression
  • Confusion/Memory impairment
  • Severe muscle stiffness
  • Seizures
  • Hallucinations (Psychosis)

Here are some additional side effects of Zoloft vs Paxil to be aware of:

  1. Weight Gain: Paxil may cause more weight gain than Zoloft. It’s important to monitor your weight while taking these medications and discuss any concerns with your healthcare provider.
  2. Tapering Off: When discontinuing the drug, Zoloft is better tolerated than Paxil. This means that tapering off Zoloft may result in fewer withdrawal symptoms compared to Paxil. It’s always recommended to gradually reduce the dosage under the guidance of your healthcare provider.
  3. Additional Side Effects: Both medications may have side effects beyond those mentioned. If you experience any new or worsening symptoms, it’s important to consult your healthcare provider.

Warnings and Precautions

If you’re pregnant or planning to become pregnant, it’s important to discuss the potential risks and benefits of taking selective serotonin reuptake inhibitors with your healthcare provider.

It is also important to note that Zoloft or Paxil may interact with other medications, such as blood thinners and nonsteroidal anti-inflammatory drugs (NSAIDs).

Read this case report I published about a drug interaction in an older adult between sertraline and phenytoin, a common seizure medication.

Your healthcare provider will be able to determine if any potential drug interactions may occur and if any adjustments to your treatment plan are necessary.

Furthermore, if you experience any unusual or severe side effects while taking Paxil or Zoloft, it’s important to contact your healthcare provider immediately.

However, it’s important not to stop taking these medications abruptly without consulting your healthcare provider, as this may lead to withdrawal symptoms.

Your healthcare provider can guide you on safely discontinuing your antidepressant if needed.


In conclusion, when comparing Paxil and Zoloft, both medications have shown similar effectiveness in treating depression and other mental health conditions.

However, they do have common side effects, and there are some differences between paroxetine and sertraline.

It’s important to consider the difference in their half-lives and also the pregnancy classifications.

By discussing these factors with your healthcare provider, you can decide whether Zoloft or Paxil is better for you.

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