Key takeaways

Zoloft (sertraline) is prescribed for various disorders, including depression and anxiety, but it may not be effective for everyone. Alternatives include Lexapro, Prozac, Effexor, Cymbalta, and Wellbutrin.
Only 60% to 70% of patients respond to antidepressant therapy like Zoloft, prompting the exploration of other antidepressants or natural remedies to alleviate symptoms.
Alternatives to Zoloft include other SSRIs, SNRIs, atypical antidepressants, TCAs, MAOIs, and natural options like St. John’s wort, SAMe, omega-3 fatty acids, and vitamin D supplements.
Transitioning to a Zoloft alternative requires careful consideration of side effects, lifestyle compatibility, cost, and potential withdrawal symptoms. A gradual dose reduction is recommended to minimize discontinuation syndrome.

Individuals with depression or anxiety may be prescribed a medication called Zoloft (sertraline). Zoloft belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which increase 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 fact, only 60% to 70% of patients with depression respond to antidepressant therapy. For others, Zoloft does not effectively treat symptoms of depression or it can cause significant drug interactions. Serious side effects such as suicidal thoughts, serotonin syndrome, bleeding, and seizures may also occur. In these cases, a healthcare provider may suggest a different type of antidepressant to try. There are also non-medicine treatments and natural alternatives to Zoloft that help ease depressive feelings and improve quality of life.

What can I take in place of Zoloft?

There are other options available to treat depression and anxiety disorders that do not improve with Zoloft. These alternative prescription medications include other types of SSRIs or other classes of antidepressants such as serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). These options may be more suitable for certain individuals due to their different uses, side effect profiles, and dosages.

Compare Zoloft alternatives
Drug name	Uses	Side effects	Dosage	Get coupon
Zoloft (sertraline)	Depression, anxiety, OCD, PTSD, PMDD	Diarrhea, dizziness, dry mouth, headache, insomnia, nausea	50-200 mg daily	Get Zoloft coupons
Celexa (citalopram)	Depression	Diarrhea, dry mouth, insomnia, nausea, sweating, tremor	20-40 mg daily	Get Celexa coupons
Cymbalta (duloxetine)	Depression, anxiety, pain	Constipation, drowsiness, dry mouth, fatigue, sweating	40-60 mg daily	Get Cymbalta coupons
Desyrel (trazodone)	Depression	Fatigue, sedation, sexual dysfunction, weight loss	150-400 mg daily in divided doses	Get Desyrel coupons
Effexor XR (venlafaxine)	Depression, anxiety	Constipation, drowsiness, dry mouth, nausea, sweating	75-225 mg daily	Get Effexor XR coupons
Lexapro (escitalopram)	Depression, anxiety	Diarrhea, dry mouth, headache, insomnia, nausea, sweating	10-20 mg daily	Get Lexapro coupons
Marplan (isocarboxazid)	Depression	Drowsiness, dry mouth, headache, high blood pressure	20-60 mg daily in divided doses	Get Marplan coupons
Pamelor (nortriptyline)	Depression	Constipation, blurred vision, dry mouth, urinary retention	25 mg three or four times daily	Get Pamelor coupons
Paxil (paroxetine)	Depression, anxiety, OCD, PTSD, PMDD	Dizziness, dry mouth, insomnia, nausea, sweating, tremor	10-60 mg daily	Get Paxil coupons
Pristiq (desvenlafaxine)	Depression	Constipation, dizziness, insomnia, nausea, sweating	50 mg daily	Get Pristiq coupons
Prozac (fluoxetine)	Depression, anxiety, OCD, PMDD, bulimia	Diarrhea, dry mouth, headache, insomnia, nausea	10-80 mg daily	Get Prozac coupons
Trintellix (vortioxetine)	Depression	Constipation, diarrhea, dizziness, dry mouth, nausea, vomiting	10-20 mg daily	Get Trintellix coupons
Wellbutrin XL (bupropion)	Depression, seasonal depression	Constipation, dry mouth, headache, insomnia, nausea	300 mg daily	Get Wellbutrin XL coupons
Xanax (alprazolam)	Anxiety	Confusion, drowsiness, memory problems, weight gain	0.25 mg three times daily	Get Xanax coupons

Other alternatives to Zoloft

Top 5 Zoloft alternatives

Any of the antidepressants above may be prescribed if Zoloft is not working for anxiety or depression. However, the following prescription drugs are the most common alternatives.

1. Lexapro

Zoloft and Lexapro are both SSRIs indicated for the treatment of depression. Lexapro is also used for 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 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. Prozac

Prozac is another SSRI medication that works in the same way as Zoloft to increase serotonin activity. Prozac and Zoloft are both approved by the Food and Drug Administration (FDA) to treat depression, panic disorder, OCD, and PMDD. Additionally, Prozac is approved for the eating disorder 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

If an SSRI like Zoloft does not improve symptoms, your healthcare provider may suggest trying a different class of antidepressants called SNRIs. SNRIs increase levels of norepinephrine as well as serotonin, so they may be more effective for some patients. Effexor is one such medication that is indicated for the treatment of depression and anxiety disorders. SNRIs overall are associated with more frequent side effects than SSRIs, and Effexor, in particular, may increase blood pressure when given at high doses up to 225 mg per day (extended-release version).

RELATED: Effexor vs. Zoloft

4. Cymbalta

Cymbalta is another SNRI medication. Unlike Zoloft, Cymbalta is also approved to treat nerve pain and 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 Cymbalta include gastrointestinal disturbances and headache, but it is generally well-tolerated. Cymbalta is usually started at a dose of 40 to 60 mg daily.

RELATED: Cymbalta vs. Zoloft

5. Wellbutrin

Wellbutrin has a different mechanism of action than Zoloft and works as a dopamine and norepinephrine reuptake inhibitor. What’s unique about Wellbutrin is that it is less likely to cause weight gain or sexual dysfunction compared to other antidepressant drugs. In a clinical study comparing antidepressant use and weight changes, Wellbutrin was found to cause weight loss and Zoloft was associated with weight gain. Wellbutrin XL has a target dose of 300 mg daily, and it may be more suitable for certain patients due to its better side effect profile.

RELATED: Wellbutrin vs. Zoloft

Natural alternatives to Zoloft

There are several natural alternatives to Zoloft that may offer some relief of depression and anxiety. “Natural antidepressants refer to herbal and other remedies that occur in nature or which your body could produce itself,” says Carrie Lam, MD, family physician at Lam Clinic in California. “Much evidence-based literature suggests that natural antidepressants are effective in dealing with depression and other mental health issues like anxiety.”

Some common natural antidepressants include the following vitamins, supplements, and alternative remedies:

St. John’s wort: One herbal supplement that elevates mood is St. John’s wort. In a 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.
S-adenosyl-L-methionine (SAMe): SAMe is a compound that occurs naturally in the body and has been studied as a supplement to treat osteoarthritis and depression. Evidence of its efficacy is promising but inconclusive. However, SAMe has been shown to cause fewer side effects and drug interactions compared to prescription drugs.
Omega-3 fatty acids: Individuals with mental health issues may have low levels of omega-3 fatty acids. Omega-3s are found in fish oil, and populations that consume large amounts of fatty fish have a lower prevalence of mood disorders. Omega-3s are available in supplements and foods such as salmon, mackerel, and flaxseed.
Vitamin D: “A lack of vitamin D is one of the most common contributors to depression. Vitamin D deficiency is pretty common because most people don’t get enough vitamin D,” says Stephanie Seitz, ND, a naturopathic doctor at Natural Kid Doc in Arizona. “Your body can create vitamin D so sunlight and supplements are a natural alternative to antidepressants.”
Talk therapy: Speaking with a mental health specialist can improve depression and anxiety symptoms and provide an important addition or alternative to drug therapy. One common type of talk therapy 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.

Natural remedies are not a replacement for diagnosis and treatment from a medical professional. Natural does not always mean safe, and many dietary supplements are not monitored by the FDA in the same way prescriptions drugs are. In addition, herbal supplements can interfere with other medications and cause dangerous interactions. Consult your healthcare provider for medical advice before starting any natural therapies.

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 you experienced while taking your current medication
What symptoms did not get better on your 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 (generic drugs are typically cheaper than brand-name versions)

It’s also important to consider the risks of stopping Zoloft before switching to an alternative medication. “Many people experience withdrawal symptoms while weaning off antidepressant medications,” Dr. Lam says. These withdrawal symptoms occur during discontinuation syndrome when Zoloft is stopped abruptly. Common signs of discontinuation syndrome include:

Nausea
Sweating
Irritability
Dizziness
Tremor
Anxiety
Confusion
Insomnia
Flu-like symptoms

To avoid Zoloft withdrawal, a gradual reduction in dose is 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.