11 Alternatives to Zoloft

Published on: 18 Oct 2023
Clinically Reviewed by Elizabeth Keohan, LCSW-C
11 Alternatives to Zoloft

Zoloft (or the generic version, sertraline) is an antidepressant in the class of drugs known as selective serotonin reuptake inhibitors (SSRIs). Zoloft is considered a first-line treatment for depression and some anxiety disorders. Still, while studies show it can be very effective in relieving symptoms for some people, Zoloft use isn’t right for everyone. The drug won’t necessarily work the same way for every person — things like age, weight, severity of symptoms, and other factors can change the results of a drug from person to person. 

If your doctor has prescribed Zoloft (sertraline) but you’re not seeing the outcome you want, the side effects are too much for you to handle, or you’re hoping to find a more natural way to address your mental health, it might be time to look into Zoloft alternatives. 

While one can find Zoloft online, many people today seek a holistic approach to treating their mental health — entirely or in addition to a traditional treatment plan. Fortunately, options are available if you want to find alternatives to Zoloft for anxiety and depression. Read on for information about Zoloft substitute options, both through medication and with natural methods.  

Alternative Medications to Zoloft

If you’re looking for a new medication because you have difficulty with Zoloft side effects or are experiencing subpar improvement in symptoms, there are other SSRI medications you can try. All SSRIs work the same way, but different drugs can produce different results. 

SSRIs you might want to try instead of Zoloft include:

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1. Prozac (fluoxetine)

Prozac is an effective SSRI that’s been prescribed for decades. Like Zoloft, Prozac blocks serotonin reuptake, increasing levels to improve mood and energy levels and regulate emotion. 

Prozac can be used for:

2. Celexa (citalopram)

Celexa is yet another antidepressant medication that’s widely used and typically an effective option for treating severe depression. Celexa can reduce symptoms of depression and other conditions by restoring chemical balance in the brain.

Celexa can be used for:

  • Major depressive disorder (MDD)
  • Generalized anxiety disorder (GAD) 
  • Obsessive-compulsive disorder (OCD)
  • Social phobia
  • Panic disorder
  • Post-traumatic stress disorder (PTSD)
  • Bulimia

3. Lexapro (escitalopram)

Lexapro is used to treat anxiety and severe depression in some people. It’s known to regulate mood and reduce depressive or anxiety symptoms.

Lexapro can be used for:

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

Some research shows Lexapro might improve insomnia or other sleep disorders.

4. Paxil (paroxetine)

Paxil, another SSRI antidepressant, is FDA-approved to treat several mental health conditions, including depression and certain anxiety disorders. In some people, Paxil relieves sadness and improves mood while reducing worry or anxiety. 

Paxil can be used for:

  • Major depressive disorder (MDD)
  • Obsessive-compulsive disorder (OCD)
  • Generalized anxiety disorder (GAD)
  • Premenstrual dysphoric disorder (PMDD)
  • Panic disorder
  • Post-traumatic stress disorder (PTSD)
  • OCD in children
  • Bipolar depression
  • Premenstrual syndrome
  • Irritable bowel syndrome

Alternatives to SSRIs to Replace Zoloft

SSRIs are not the only medication known to treat symptoms of anxiety or depression effectively. Several other classes of drugs can be effective for some people. If you’re looking for Zoloft alternatives that are not SSRIs, ask your doctor about the following classes of drugs.

5. Serotonin and norepinephrine reuptake inhibitors (SNRIs)

  • Cymbalta (duloxetine)
  • Pristiq (desvenlafaxine)
  • Effexor XR (venlafaxine)

6. Monoamine oxidase inhibitors (MAOIs)

  • Emsam (selegiline)
  • Parnate (tranylcypromine)
  • Marplan (isocarboxazid)

7. Tricyclic antidepressants (TCAs)

  • Norpramin (desipramine)
  • Pamelor (nortriptyline)

8. Atypical antidepressants

  • Wellbutrin (bupropion)
  • Remeron (mirtazapine)
  • Trazodone
  • Trintellix

Natural Alternatives to Zoloft

The popularity of natural treatments in the mental health field has increased over the years. Holistic approaches — including talk therapy, lifestyle modifications, and herbal supplements — may help alleviate symptoms related to mental health conditions without causing some of the side effects that Zoloft or other medications might have. 

9. Talk therapy (psychotherapy)

Talk therapy effectively treats depression, anxiety disorders, and other mental health conditions. Research shows that combining talk therapy with medication can produce far superior results than when one or the other is used alone. 

Cognitive behavioral therapy (CBT) has significantly improved the treatment of anxiety and depression. By identifying negative thought and behavior patterns, you can develop healthier coping mechanisms to change your reaction to people and situations.

10. Lifestyle changes

Making lifestyle changes — in addition to, or in an attempt to stop taking, medication — can profoundly impact overall well-being. For some people, an active approach to mental health can reduce or eliminate the need for other medicines.

Physical activity releases endorphins — the body’s natural mood enhancers — and has been found in studies to reduce stress and anxiety. Additionally, maintaining a focus on balanced nutrition ensures you get nutrients vital for brain function.

Other lifestyle changes that can be effective in managing symptoms of depression or anxiety include:

  • Maintaining a healthy sleep habit
  • Mindfulness practices like meditation
  • Yoga
  • Deep breathing exercises
  • Journaling 

11. Herbal supplements

The role of herbal supplements in treating depression and anxiety has become more popular. Some natural or herbal supplements that are believed to help reduce depression and anxiety symptoms potentially include:

*NOTE: You should not replace a prescribed treatment plan with herbal supplements without first talking to your doctor or mental healthcare provider. Never stop taking medication without discussing an appropriate taper plan to avoid Zoloft withdrawal

“Natural alternatives that have shown proven benefits similar to Zoloft include talk therapy and exercise. Talk therapy can help address the current stressors and provide coping skills to better the mood. Exercise can boost endorphins, provide better sleep and improve energy. All of these exercise benefits can help to alleviate symptoms of depression and anxiety.”

Talkspace psychiatrist Dr. Dion Metzger

Considerations for Switching to a Zoloft Alternative

Before switching any aspect of your prescribed treatment plan, it’s essential to talk to your doctor. You can discuss potential alternatives to Zoloft for anxiety, depression, or other mental health conditions. 

Before switching from Zoloft to another antidepressant or form of treatment, several factors must be considered.

Evaluate current health status

Current health plays an integral role in determining which medication would be best for treating your symptoms. It’s also important to disclose any current prescription drugs you’re taking to your doctor, so they can evaluate potential adverse side effects if you combine existing medications with a new regimen.

Side effects can be especially critical if you have specific health conditions like heart disease or diabetes. Even if you previously did so, review your full medical history with your healthcare provider as you discuss alternatives to Zoloft.

Look at potential side effects

All medications and even supplements have the potential for side effects, and not all known side effects will be felt by everyone. Side effects can range from mild inconveniences – like dry mouth or drowsiness, to severe concerns – like weight gain or sexual dysfunction, to serious or life-threatening concerns — like allergic reactions, chest pain, or thoughts of suicide. 

Understanding a drug’s unique profile and warnings can help manage expectations as you compare one drug against another to evaluate the benefits against any potential side effects you might experience.

Determine the efficacy of new medication or treatment

People can respond very differently to the same medication. Biological body chemistry, genetics, weight, age, and severity of symptoms can all impact the efficacy of any drug. In short, what works great for one person may not work at all for another.  

Be sure to talk to your doctor about what you should expect from a new medication or treatment, including how long it will typically take before you start seeing results. This will help you monitor how well a new treatment plan is working.

Evaluate the cost

Cost can be a huge barrier to treatment for many people. It’s important to know that the cost of medications can vary depending on whether they’re brand-name or generic, the dosage, and where you fill them. 

Sometimes, the same drug at different pharmacies — even in the same town — can have different prices. Be sure to ask your pharmacy for an estimate on cost before you fill a prescription and inquire about drug manufacturer discounts, coupon cards, or other ways to reduce the price of a new drug if cost is a factor.

Find the Right Alternative with Talkspace Psychiatry

Navigating alternatives to Zoloft can be a long and confusing process. Talkspace can help you with the transition. 

If you’re looking for a Zoloft substitute but aren’t sure where to start, Talkspace offers professional guidance and support from licensed online psychiatrists skilled in managing mental health condition treatment plans. Whether you need help treating depression, panic disorder, obsessive-compulsive disorder, or other mental health conditions, Talkspace is here to help. Reach out to Talkspace today.  


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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.

Articles contain trusted third-party sources that are either directly linked to in the text or listed at the bottom to take readers directly to the source.

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