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Key takeaways
Zoloft is an antidepressant medication called an SSRI. It’s FDA-approved to treat depression, anxiety, obsessive-compulsive disorder, and other psychiatric medical conditions.
Antidepressants don’t always work, and the adverse effects can sometimes be hard to live with. Switching to another drug requires the medical advice of a healthcare professional.
Alternatives to Zoloft include other antidepressants or anxiety medications.
Zoloft (sertraline) is a brand-name prescription antidepressant that treats depression or anxiety. As a selective serotonin reuptake inhibitor (SSRI), Zoloft increases serotonin levels in the brain to improve mood. Along with major depressive disorder (MDD), Zoloft also treats panic disorder (PD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD). Zoloft may not work for everyone. In cases where Zoloft doesn’t work or causes intolerable side effects, a healthcare provider may suggest a different type of antidepressant or anxiety medication or a nonpharmaceutical treatment.
What can I take instead of Zoloft?
Alternative prescription medications that treat depression include other types of SSRIs, other classes of antidepressants such as serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, atypical antipsychotics, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). For anxiety, treatment options include other SSRIs, SNRIs, buspirone, TCAs, and benzodiazepines. These options may be more suitable for certain individuals due to their different uses, side effect profiles, and dosages.
Compare Zoloft alternatives |
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|---|---|---|---|
| Drug name | Price without insurance | SingleCare price | Savings options |
| Zoloft | $544 for 30, 50 mg tablets | $9 for 30, 50 mg tablets of generic sertraline at Kroger | See latest prices |
| Lexapro (escitalopram) | $564 for 30, 10 mg tablets | $9 for 30, 10 mg tablets of generic escitalopram at Kroger | See latest prices |
| Fluoxetine | $68 for 30, 20 mg capsules | $6 for 30, 20 mg capsules of generic fluoxetine at Kroger | See latest prices |
| Effexor XR (venlafaxine extended-release) | $779 for 30, 150 mg capsules | $6 for 30, 150 mg capsules of generic venlafaxine ER at Kroger | See latest prices |
| Duloxetine | $229 for 30, 60 mg capsules | $8 for 30, 60 mg capsules of generic duloxetine at Kroger | See latest prices |
| Wellbutrin XL | $3,636 for 30, 300 mg tablets | $9 for 30, 300 mg tablets of generic bupropion ER at Kroger | See latest prices |
| Paxil | $756 for 30, 20 mg tablets | $4 for 30, 20 mg tablets of generic paroxetine at Walmart | See latest prices |
| Celexa (citalopram) | $407 for 30, 20 mg tablets | $6 for 30, 20 mg tablets of generic citalopram at Kroger | See latest prices |
| Pristiq (desvenlafaxine ER) | $543 for 30, 100 mg extended-release tablets | $18 for 30, 100 mg tablets of generic desvenlafaxine ER at Kroger | See latest prices |
| Trintellix
(vortioxetine) |
$677 for 30, 20 mg tablets | $466 for 30, 20 mg tablets of brand-name Trintellix at Kroger | See latest prices |
| Viibryd | $434 for 30, 40 mg tablets | $36 for 30, 40 mg tablets of generic vilazodone at CVS Pharmacy | See latest prices |
| Trazodone | $38 for 30, 50 mg tablets | $6 for 30, 50 mg tablets of generic trazodone at Kroger | See latest prices |
| Remeron | $246 for 30, 15 mg tablets | $9 for 30, 15 mg tablets of generic mirtazapine at Kroger | See latest prices |
| Amitriptyline | $27 for 30, 25 mg tablets | $4 for 30, 25 mg tablets of generic amitriptyline at Walmart | See latest prices |
| Buspirone | $46 for 60, 5 mg tablets | $5 for 60, 5 mg tablets of generic buspirone at Kroger | See latest prices |
Prescription drug prices often change. These are the most accurate medication prices at the time of publishing in ZIP code 23666 as of 12/16/2025. The listed price without insurance references the price of brand-name drugs (unless otherwise specified). The listed SingleCare price references the price of generic drugs if available. Click the link under “Savings options” to see the latest drug prices.
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Top 5 Zoloft alternatives
Any of the prescription medications above may be prescribed if Zoloft is not working for anxiety or depression. However, the following prescription drugs are some of the most common alternatives.
1. Lexapro (escitalopram)
Zoloft and Lexapro are both SSRIs indicated for the treatment of depression. Lexapro is also FDA-approved to treat generalized anxiety disorder. Because both medications belong to the same drug class, they have similar side effects such as headache, nausea, and insomnia. Lexapro was shown in some, but not all, clinical studies to be more effective in treating depression and better tolerated than Zoloft. The standard dose for Lexapro is 10 mg daily with a maximum dose of 20 mg per day.
RELATED: Lexapro vs. Zoloft
2. Fluoxetine
Better known as Prozac, its original but discontinued brand-name version, fluoxetine is another SSRI medication that works in the same way as Zoloft to increase serotonin activity. Like Zoloft, fluoxetine is approved by the Food and Drug Administration (FDA) to treat depression, panic disorder, and OCD. Additionally, fluoxetine is approved to reduce binge-eating and vomiting in people with bulimia nervosa. Both drugs are similar in effectiveness for depressive symptoms, but Prozac has a lower risk of causing diarrhea compared to Zoloft. The standard dose for Prozac is 20 mg daily and should not exceed 80 mg per day.
RELATED: Prozac vs. Zoloft
3. Effexor or Effexor XL (venlafaxine)
If an SSRI like Zoloft does not improve symptoms, your healthcare provider may suggest trying a different class of antidepressants called SNRIs. These drugs increase levels of norepinephrine as well as serotonin, so they may be more effective for some patients. Effexor XR is one such medication that is indicated for the treatment of depression and anxiety disorders. SNRIs overall are associated with certain specific side effects more frequently than SSRIs; Effexor XR, in particular, may increase blood pressure, more so when given at higher doses, with the usual dose range going from 75 to 225 mg per day (extended-release version).
RELATED: Effexor vs. Zoloft
4. Duloxetine
Duloxetine is another SNRI medication, but people may know it better under its original but discontinued brand name, Cymbalta. Unlike Zoloft, duloxetine is also prescribed for nerve pain or chronic pain in addition to depression and anxiety. Therefore, Cymbalta may be more therapeutic in individuals who have both depression and pain symptoms. Common side effects of duloxetine include gastrointestinal disturbances and headache, but it is generally well-tolerated. Cymbalta is usually started at a dose of 30 to 60 mg daily.
RELATED: Cymbalta vs. Zoloft
5. Wellbutrin or Wellbutrin XL (bupropion)
Wellbutrin XL has a different mechanism of action than Zoloft. It’s a norepinephrine and dopamine reuptake inhibitor (DNRI). DNRIs are typically stimulants, so bupropion doesn’t have many of the sedative effects of other antidepressants. It is also less likely to cause sexual dysfunction or weight gain. In fact, people on Wellbutrin are more likely to lose weight than to gain weight, a common side effect of antidepressants. Wellbutrin XL has a typical dose of 150 to 300 mg daily, and it may be more suitable for certain patients due to its different side effect profile.
RELATED: Wellbutrin vs. Zoloft
Over-the-counter depression or anxiety medications
There are many over-the-counter medications and supplements that promise improved mood. Some do work, but not enough to adequately relieve the symptoms of clinical depressive or anxiety disorders. The American Psychiatric Association (APA) guidelines for treating major depressive disorder only recommend St. John’s wort. In a 2008 systematic review of its use in patients with major depression, St. John’s wort was found to be similarly effective as standard antidepressants. However, this supplement has significant drug interactions and can reduce the effectiveness of other drugs when taken together.
Other possible OTC supplements that may improve mood include creatinine, carnitine, glycyrrhizic acid, omega-3 fatty acids, S-adenosyl-L-methionine (SAMe), and zinc. The evidence for the effectiveness of these supplements is not definitive, so they are not recommended in the APA guidelines. Because supplements are not reliable and may have drug interactions, always get medical advice from a healthcare professional before starting any new supplements.
Natural alternatives to Zoloft
There are several natural alternatives to Zoloft that may offer some relief from depression and anxiety:
- Talk therapy: Speaking with a mental health specialist can improve depression and anxiety symptoms and provide an important addition or alternative to drug therapy. The most effective psychotherapy, and one widely recommended in the APA guidelines, is cognitive-behavioral therapy (CBT), which focuses on changing negative thoughts and behaviors.
- Exercise: Regular exercise has been shown to boost endorphins, improve sleep, and increase serotonin function in the brain.
- Sleep: Adopting good sleep hygiene can significantly improve the quality of sleep, which in turn greatly enhances mood.
- Dietary changes: A diet high in omega-3 fats and tryptophan could be associated with better mood.
- Alternative treatments: The APA guidelines suggest considering yoga, acupuncture, or bright light therapy as possibly helpful for depression.
For clinical mood disorders or serious mental health conditions like OCD, natural remedies are not a replacement for diagnosis and treatment from a medical professional. Consult a healthcare provider for medical advice before starting any natural therapies.
RELATED: The best diet for depression
How to switch to a Zoloft alternative
If Zoloft is not working well for you or improving your quality of life, it may be time to switch to an alternative. However, there are several things to consider before deciding to make this change. Alternative medications may have different side effects and benefits, and some treatments may fit your lifestyle and values more than others. Cost is another factor to think about because depression treatments are usually given long-term. Before making any medication changes, talk to your healthcare provider about the following:
- Side effects experienced with the current medication
- What symptoms did not get better on the current medication
- Any part of your lifestyle or schedule that makes one treatment option easier than another
- If you are interested in supplements or alternative remedies that might help your symptoms
- The cost of any potential medication or therapy
To avoid withdrawal symptoms, a gradual reduction in dose is often recommended instead of abrupt discontinuation. Make sure to follow your healthcare provider’s instructions about how to safely taper off Zoloft. Your healthcare provider can also help you navigate different treatment options to find the right one that suits your needs and goals.
Choosing the right path for depression treatment
Depression treatment always starts with talking with a healthcare professional. The key insight about depression is that patients aren’t thinking or acting the way they normally do, so it helps to listen to the medical advice of a trained professional. For clinical depression, often the best way to start is with pharmaceutical treatment. It will take a while to get the right drug and dosage that balances effectiveness with possible side effects. Pills are often not enough, so a commitment to psychotherapy is key to overcoming clinical depression. All of this takes time. The drugs take weeks or months. Psychotherapy can take longer. The only way to succeed is to continue to work with your healthcare team on finding the best treatment regimen for you.
Expert takeaway
“Based on a long track record of safety and effectiveness, Zoloft ranks among the commonly prescribed antidepressants, as well as drugs overall, in the country,” says Chad Shaffer, MD, member of the SingleCare Medical Board. “When it is ineffective or not tolerated, a trial of a different SSRI, if two have not already been tried, an SNRI, or bupropion is often recommended.”
The SingleCare prices in this article are the most accurate at the time of publishing in ZIP code 23666 as of 12/16/2025. Prices vary by pharmacy. Visit our Zoloft coupon page for updated Zoloft prices near you.
- A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?, International Clinical Psychopharmacology (2014)
- Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: A randomized trial, JAMA (2001)
- Risks of digestive system side-effects of selective serotonin reuptake inhibitors in patients with depression: A network meta-analysis, Therapeutics and Clinical Risk Management (2022)
- Long-term weight change after initiating second-generation antidepressants, Journal of Clinical Medicine (2016)
- APA Clinical practice guideline for the treatment of depression across three age cohorts, American Psychiatric Association (2019)
- St. John’s wort for major depression, Cochrane Database of Systematic Reviews (2008)
- A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder, The American Journal of Psychiatry (2012)
- Acetyl-l-carnitine supplementation and the treatment of depressive symptoms: A systematic review and meta-analysis, Biopsychosocial Science and Medicine (2018)
- Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial, Journal of Affective Disorders (2020)
- International Society for Nutritional Psychiatry research practice guidelines for omega-3 fatty acids in the treatment of major depressive disorder, Psychotherapy and Psychosomatics (2019)
- Practice guideline for the treatment of Major Depressive Disorder, 3rd ed., American Psychiatric Association (2010)
- Efficacy of adding nutritional supplements in unipolar depression: A systematic review and meta-analysis, European Neuropsychopharmacology (2017)
- Tryptophan intake in the US adult population is not related to liver or kidney function but is associated with depression and sleep outcomes, Journal of Nutrition (2016)