Effexor vs Zoloft: What Are The Differences?

Kristin Hall

Reviewed by Kristin Hall, FNP

Written by Geoffrey C. Whittaker

Published 07/08/2022

Updated 07/09/2022

Antidepressants are a complicated medication — even the simplest definition uses words like “neurotransmitter” casually, and that can leave a lot of average people confused. 

It gets even harder when it’s your own mental health at stake in the matter — how are you supposed to advocate for yourself when you don’t know the first thing about the differences between TCAs and MAOIs and SNRIs and SSRIs? What even are MAOIs and SNRIs and SSRIs? How do you know whether your healthcare provider is making the right choice between two different pills? Norepinephrine vs serotonin, Effexor® vs Zoloft®?

Feeling anxious about medications is the common and obvious outcome when we don’t feel confident about the decisions we make — or are allowed to be made for us. 

If you’re struggling with this question yourself, you’ve probably been doing your fair share of Internet research to find the right answer. We may not have the “answer” for you, but we can help you clearly understand these two medications in comparison.

Let’s start with the most obvious question: what makes them different?

Let’s talk about sertraline and venlafaxine — the generic versions of Zoloft and Effexor, respectively. 

Sertraline is an antidepressant of the selective serotonin reuptake inhibitor, or SSRI, family. It’s generally considered safe and effective and works by helping you moderate the levels of serotonin available in your brain, thereby evening out your moods. 

Venlafaxine, which is not a fax machine manufacturer, but an SNRI (select norepinephrine reuptake inhibitor), moderates levels of serotonin and dopamine (which doesn’t get included in the initials) to help stabilize your moods.

That’s the mile-high view. Let’s get a little closer.

What Are Zoloft and Effexor Used For?

Both Zoloft and Effexor are used to treat depression symptoms and signs of depression in individuals suffering from depressive disorders, but this is where the similarities arguably stop. 

Zoloft can be prescribed for OCD (obsessive-compulsive disorder), panic disorder and PTSD (post-traumatic stress disorder). 

In an off-label capacity, it can also be prescribed to treat binge eating disorders and body dysmorphic disorders, as well as forms of bulimia and generalized anxiety disorder. 

It may also be used to treat premenstrual dysphoric disorder and social anxiety

Effexor, on the other hand, can be used for depression, social anxiety, ADD, neuropathy, hot flashes, migraines and PTSD.

Side Effects of Zoloft vs Effexor

Zoloft side effects include diarrhea, nausea, vomiting, constipation, insomnia or difficulty falling asleep, dry mouth and heartburn, weight changes, headaches, anxiety, change in libido, excess sweating or uncontrollable shaking. Rashes, confusion, difficulty breathing, abnormal bleeding or bruising and hallucinations are also possible. 

Effexor shares many of these common side effects, and may also result in weight loss, blurred vision or seizures.

Both medications can cause a potentially fatal condition called serotonin syndrome if stopped without care or caution, so be sure to speak to your healthcare provider before stopping either medication.

Dosages of Zoloft vs Effexor

Sertraline is an oral medication, and in tablet or capsule form it can be administered in doses between 25mg and 20mg. 

That may look very different depending on the purpose — OCD and depression treatment comes in around 50mg, whereas lower doses are where you’ll typically start for PTSD and SAD. 

Generally, dosage will increase by 50mg (or more) per week until your healthcare provider finds the ideal dosage.

Effexor is considered more of an SSRI at low doses — it’s not until higher doses that the norepinephrine effects come into play. 

Generally, oral venlafaxine is available from 25mg up to 225mg, depending on whether it’s regular or extended release. 

You’ll likely start taking 75mg, but never exceed 375mg for safety reasons.

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Which of these medications is right for you? It could be both. It could be neither. It could take time to answer that question. Medical conditions, frequency (and intensity) of depressive episodes and medical history are different for everyone.

In the big picture, no one medication is empirically better for your needs (or easier on side effects) than another. 

Depression isn’t a one-size-fits-all kind of mental health condition (there are few, if any, of those, anyway). When you have one of the many types of depression like major depression, your symptoms of depression might differ greatly from the next person’s. Even if they’re the same, your body and brain chemistry might require a different treatment to see results. 

And depression affects people differently. 

Some people experience sleep issues or irritability, weight fluctuations, increased risk-taking and plenty of other symptoms. Medications are designed to do one thing, but the right one is selected to help treat your symptoms through your brain.

What we’re getting at here is that you can’t figure out whether Zoloft or Effexor is right for you from reading about them here. You may need to try one and, if it fails to help you, try the other. You may end up with a different medication altogether by the time you find the right medication for your needs. 

And you know what? Medication might only be part of the total treatment package.

Let’s put pills aside for a second. Even if you find the right medication for your needs, depression and other mood disorders may not be treated effectively with medication alone. 

That’s why it’s common to see medical professionals create a tailored treatment package that includes not just medication, but therapy and lifestyle changes.

Therapy may be your best asset that doesn’t come in a pill bottle. These days, the go-to, proven therapeutic format is something called Cognitive Behavioral Therapy (CBT), which teaches depressed people how to recognize depressive thoughts and resist them, eventually learning to control them altogether.

Therapy is great for the mind part of things, but you can do more for your body than just take pills, too. 

Most health care providers will recommend at least some lifestyle changes if you’re diagnosed with depressive disorder. 

These may include improving your diet, increasing your exercise, getting more sleep, getting drunk less, putting a stop to smoking, and spending more time embracing your social life.

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Antidepressant drugs are an increasingly dense field of increasingly similar medications, and we’re likely meeting here because you’re preparing your information before taking a prescription for antidepressants. That’s good — it’s important to be educated and understand your options. 

What’s more important, though, is involving a healthcare professional in those conversations. 

Because your healthcare provider may see things you don’t, they’ll ultimately help you make the right choices and determine whether one medication or another offers your brain the best treatment.

If you’re ready to have those conversations, consider hers’ online psychiatry as a way to speak to a healthcare provider right now. 

Whether you get your mental health journey started with us or elsewhere, do it now. And keep an open mind — there are more effective medications than you think!

Learn about Effexor and another popular antidepressant here: Cymbalta vs Effexor: What Are The Similarities & Differences?

6 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

  1. Craft, L. L., & Perna, F. M. (2004). The Benefits of Exercise for the Clinically Depressed. Primary care companion to the Journal of clinical psychiatry, 6(3), 104–111.
  2. Ng, C. W., How, C. H., & Ng, Y. P. (2017). Managing depression in primary care. Singapore medical journal, 58(8), 459–466.
  3. Depression Basics. (n.d.). Retrieved January 08, 2021, from
  4. U.S. National Library of Medicine. (n.d.). Venlafaxine: MedlinePlus Drug Information. MedlinePlus.
  5. Singh HK, Saadabadi A. Sertraline. [Updated 2020 Nov 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
  6. U.S. National Library of Medicine. (n.d.). Sertraline: MedlinePlus Drug Information. MedlinePlus.

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Kristin Hall, FNP

Kristin Hall is a board-certified Family Nurse Practitioner with decades of experience in clinical practice and leadership. 

She has an extensive background in Family Medicine as both a front-line healthcare provider and clinical leader through her work as a primary care provider, retail health clinician and as Principal Investigator with the NIH

Certified through the American Nurses Credentialing Center, she brings her expertise in Family Medicine into your home by helping people improve their health and actively participate in their own healthcare. 

Kristin is a St. Louis native and earned her master’s degree in Nursing from St. Louis University, and is also a member of the American Academy of Nurse Practitioners. You can find Kristin on LinkedIn for more information.

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