Effexor vs Zoloft: Which is Right for Me?

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

Although Effexor and Zoloft are both prescribed to treat depression, there are some major differences between the two drugs.

In this article, we will explore the ways that Effexor and Zoloft are similar and when they may be prescribed.

We’ll also go over how they are different, common dosages, and precautions to know when taking either medication.

Plus, we’ll discuss how you should know when you should see a doctor for symptoms of depression.

What is Effexor?

Effexor (venlafaxine hydrochloride) is a serotonin and norepinephrine reuptake inhibitor (SNRI), a class of antidepressant drugs.

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Effexor uses

Effexor is approved by the Food and Drug Administration (FDA) for treatment of the following:

How Effexor works

Effexor is a serotonin and norepinephrine reuptake inhibitor (SNRI).

It works by blocking the reuptake of the neurotransmitters serotonin and norepinephrine, increasing their levels in the brain. 

Both of these neurotransmitters are important in providing feelings of balance and energy in the brain and tend to be too low in people who experience symptoms of depression, anxiety, low mood, or fatigue.

What is Zoloft?

Zoloft (sertraline hydrochloride) is a selective serotonin reuptake inhibitor (SSRI) used to treat depression and other mood disorders.

Zoloft uses

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

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

How Zoloft works

Zoloft prevents the reuptake of serotonin, which leaves more of this calming, balancing neurotransmitter in the brain.

It does not impact the other neurotransmitters, norepinephrine and dopamine.

How Are They Similar?

Effexor and Zoloft have some similarities.

  • They are both antidepressants that are taken once per day.
  • They are both FDA-approved for treating depression, panic disorder, and social anxiety disorder.

Effectiveness at treating depression

In clinical trials, Effexor was found to be superior to a placebo at treating symptoms of depression, including cognitive disturbance and anxiety.

It also led to fewer relapses.

No differences were found between sexes.

Zoloft has also been shown to be effective for treating many types of depression and mood disorders, including postpartum depression.

Both Effexor and Zoloft are effective, FDA-approved pharmaceutical options for treating depression.

Clinical trials have validated their ability to address symptoms in major depressive disorder.

Since they are in different drug classes, they work differently and one drug may be less effective for an individual than the other.

Responses to antidepressants and other pharmaceuticals depend on a person’s genetic makeup, age, weight, overall health, and other medications they may take.

How Are They Different?

Effexor and Zoloft have quite a few differences.

Drug class

Effexor is a serotonin and norepinephrine reuptake inhibitor (SNRI), whereas Zoloft is a selective serotonin reuptake inhibitor (SSRI).

These medications both work to improve the brain’s access to neurotransmitters, but Effexor works on more than one (serotonin and norepinephrine), while Zoloft only affects serotonin.

However, this does not mean that one is better than the other. 

You and your healthcare provider will decide together which medication, if any, will be best suited for you, taking into account your medical history, side effects, and risks and benefits of the medication.

Conditions treated

Effexor and Zoloft are both approved by the FDA for the treatment of the following:

  • Major depressive disorder
  • Social anxiety disorder

Effexor is also FDA-approved to treat cataplexy.

Zoloft is also an approved treatment for obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, premenstrual dysphoric disorder (PMDD), and for the treatment of OCD in children.

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

Effexor’s off-label use may include:

  • Attention deficit disorder (ADD)
  • Fibromyalgia
  • Diabetic neuropathy
  • Complex pain syndromes
  • Hot flashes
  • Migraine prevention
  • PTSD
  • OCD
  • PMDD

Off-label uses of Zoloft may include:

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

Standard dosage

Effexor and Zoloft are dosed differently.

Effexor is available as a tablet, an extended-release tablet, and an extended-release capsule.

It may be taken with or without food.

Standard dosages are 75 mg for extended-release formulations and 150 mg for the tablet.

Zoloft is available in oral tablets, capsules, and liquid solution.

It is best absorbed when taken with food. Standard dosages may range from 25-200 mg.

Potential side effects

Common side effects of Effexor include:

Common side effects of Zoloft may include:

Effexor Precautions

As an antidepressant, Effexor comes with a serious warning that includes the potential risk for increased thoughts of self-harm or suicidality.

This is called a black box warning.

This risk is greater in children, adolescents and young adults, but can happen to anyone.

If you or someone you love is taking Effexor, monitor closely for the following warning signs that require immediate medical attention:

  • Unusual changes in behavior
  • Worsening symptoms
  • Thoughts or talk of self-harm

Effexor may not be safe to take for some people.

Contraindications for Effexor include:

  • Taking MAOIs (or discontinuing MAOIs within 14 days)
  • Allergies to any ingredients in Effexor formulations
  • Abrupt withdrawal

Caution is advised in the following concurrent medical problems:

  • Seizure disorder
  • Hyponatremia or low sodium, or SIADH
  • Liver or kidney impairment
  • Bipolar disorder
  • Hypertension
  • Chronic use of NSAIDs, aspirin, or other anti-clotting medications, or bleeding disorder
  • Interstitial lung disease
  • Glaucoma

Zoloft Precautions

Zoloft also carries the serious black box warning.

Let a healthcare provider know immediately if any of the following signs develop in someone taking Zoloft:

  • Agitation, aggression, or hostility
  • Increased or worsening anxiety
  • Panic attacks
  • Irritability
  • Insomnia
  • Impulsiveness
  • Unusual changes in behavior
  • Suicidal thoughts or discussion (this risk can be increased in children, adolescents, and young adults, but can happen to anyone)
  • Restlessness
  • Manic behavior

Zoloft is contraindicated for the following reasons:

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

Always let healthcare providers know anything else that you take—even OTC drugs, herbs, or supplements.

This will help to avoid potentially serious interactions, like gastrointestinal bleeding, heart arrhythmias, serotonin syndrome, all of which can be life-threatening.

Caution is advised in the following medical conditions:

  • Medications that can increase the risk for Long QT interval
  • Family or personal history of torsades de pointes or QT prolongation
  • Arrhythmias, heart disease, or history of heart attack
  • Seizure disorder
  • Bipolar disorder
  • Glaucoma
  • Eating disorders which can cause electrolyte abnormalities
  • Increased risk of bleeding – hereditary or medication-induced (NSAIDs, aspirin, anticoagulants)
  • Hyponatremia or SIADH

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When to See a Doctor for Depression

If you are experiencing signs of depression, low mood, or do not feel like yourself, speak with your doctor.

Some signs of depression do not always make you feel sad.

You may lose interest in things you previously enjoyed, feel agitated or easily angered more often, have changes in sleep patterns or eating habits, or engage in behaviors that are not consistent with your usual activity.

There are many treatment options available for depression, both prescription and non-medication.

You are not alone in your struggle.

Your doctor can help you understand what requires treatment and will help you find treatment options that support your mood, well-being, and quality of life.

Always keep your doctor updated with how you feel, even if you already take antidepressants.

If your mood or symptoms change at any point, you may need a higher dose or a different medication.

Never stop taking antidepressants without speaking to your doctor.

They require tapering to avoid serious reactions and symptom relapse.

How K Health Can Help

Think you might need a prescription for Effexor (Venlafaxine) or a prescription for Zoloft (Sertraline)?

K Health has clinicians standing by 24/7 to evaluate your symptoms and determine which prescription is right for you.

Get started with our free assessment, which will tell you in minutes if treatment could be a good fit. If yes, we’ll connect you right to a clinician who can prescribe medication and have it shipped right to your door.


Frequently Asked Questions

Is Effexor stronger than Zoloft?
Effexor and Zoloft are different medications. They are in two different classes of drugs. Effexor works to balance the neurotransmitters serotonin and norepinephrine, while Zoloft only affects serotonin. The strength of an antidepressant in addressing your symptoms depends on your health condition and the specifics of your situation.
Is Zoloft better than Effexor for anxiety?
Neither Zoloft nor Effexor are FDA approved for treating generalized anxiety disorder. Both are approved to treat social anxiety disorder, but only Zoloft has an off-label use for treating anxiety. Generally, Zoloft is better for addressing symptoms relating to generalized anxiety.
What's the difference between Zoloft and Effexor?
Zoloft and Effexor are in different drug classes. Zoloft is an SSRI, while Effexor is an SNRI. They are approved to treat different conditions and have generally different off-label uses. While they are both approved to treat depression and social anxiety disorder, much of the similarity ends there.
Is there a better antidepressant than Effexor?
The best antidepressant for you is the one that works. This can be dependent on dosage, type of medication, length of treatment, and how your body reacts to the medication. You and your doctor will create a treatment plan that will take into account the risks and benefits of the medication options, possible interactions with your other medications, your health history, and other factors. If you start medication, it can take up to 6-8 weeks to notice improvement. Please talk to your doctor or healthcare provider about the length of treatment and how to stop the medication in the future. There are many different drug classes and types of antidepressants within each class. Effexor is an SNRI drug. The most commonly prescribed antidepressants are SSRIs, which include drugs like Zoloft, Paxil, Prozac, Celexa, and Lexapro.
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.

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