Zoloft alternatives may be considered for the treatment of mental health conditions such as depression, anxiety, and others. Other medications within the same class, selective serotonin reuptake inhibitors (SSRI), can be used, as well as medications from other classes. All have their benefits and places within treatment since treatment looks different from person to person. Non-medication options such as therapy, dietary changes, and over-the-counter options treatments may also help with depressive symptoms.
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Reasons to Consider a Zoloft Alternative
There are many reasons why a person would consider an alternative to Zoloft, an antidepressant with the active ingredient sertraline.1 While medications may provide symptom relief for some mental health conditions, they are not ‘one size fits all’ treatments. At times, a patient must consider switching to another medication because of side effects or an inadequate response to the medication.
Patients may also have preexisting conditions or other medications that conflict with the medication that they are trying to start. Depending on the condition that is to be treated, some patients may switch from Zoloft to a medication within the same class of medication, or they can try other similar antidepressants to manage their symptoms.
Other SSRIs as Zoloft Alternatives
Selective serotonin reuptake inhibitors (SSRIs) are often the first class of medications used in the treatment of depression and other psychiatric disorders, mainly due to their safety, efficacy, and tolerability, especially in comparison to older classes like MAOIs and TCAs. Outside of Zoloft, other SSRIs serve as potential alternatives. Just like Zoloft, other SSRIs tend to have similar side effects, with gastrointestinal disturbances being the most common, such as nausea and diarrhea.
This class of medication is also known to potentially cause sleep disturbances and sexual dysfunction as side effects.1,2 Many SSRIs hold multiple indications, being used to treat different disorders, and they can differ from each other. Some treat depression, while others are only used for specific disorders, such as fluvoxamine (discontinued brand name Luvox) for obsessive-compulsive disorder (OCD).
Comparing SSRIs Efficacy & Side Effects
All SSRIs are similarly effective for treating depression. Similar side effects exist between them as well due to their shared class, but some medications may be more likely to cause certain adverse effects. For example, Paxil may be more likely to cause a side effect of sexual dysfunction compared to the other SSRIs.
All of these medications can be used for depression, although it should be noted that fluvoxamine is indicated for OCD, but it can still be prescribed off-label for depression if your doctor thinks it will be beneficial for you. The response an individual has to a medication can vary from person to person, so it is important that treatments are personalized for best results.
The table below compares antidepressant alternatives to Zoloft:* 1,2,3,4,5,6,7,8
Medication Form | Common side effects | Special Considerations | |
---|---|---|---|
Sertraline (Zoloft) | Oral tablet (Zoloft, generic): 25 mg, 50 mg, 100 mg Oral capsule (generic): 150 mg, 200 mg Oral solution (Zoloft, generic): 20 mg/ml | •Nausea •Diarrhea/loose stool •Tremor •Indigestion and decreased appetite •Increased sweating •Decreased libido •Ejaculation difficulty | •Cannot be used with MAOIs or within 14 days of stopping one •Cannot be used with pimozide |
Citalopram (Celexa) | Oral tablet (Celexa, generic): 10 mg, 20 mg, 40 mg Oral capsule (generic): 30 mg Oral solution (generic): 10 mg/5 mL | •Nausea •Diarrhea •Dry Mouth •Drowsiness •Insomnia •Sweating | •Cannot be used with MAOIs or within 14 days of stopping one •Cannot be used with pimozide |
Escitalopram (Lexapro) | Oral tablet (Lexapro, generic): 5 mg, 10 mg, 20 mg Oral solution (generic): 5 mg/5 mL | •Nausea •Diarrhea •Insomnia •Drowsiness •Ejaculation difficulty •Shaking | •Cannot be used with MAOIs or within 14 days of stopping one •Cannot be used with pimozide |
Fluoxetine (Prozac, Prozac Weekly, Sarafem) | Oral tablet (generic): 10 mg, 20 mg, 60 mg Oral tablet (Sarafem): 10 mg, 15 mg, 20 mg Oral capsule (Prozac, generic): 10 mg, 20 mg, 40 mg Oral capsule, delayed release (Prozac Weekly, generic): 90 mg Oral solution (generic): 20 mg/5mL | •Nausea •Drowsiness •Insomnia •Decreased libido •Ejaculation difficulty | •Cannot be used with MAOIs or within 14 days of stopping one •Cannot be used with pimozide or thioridazine |
Paroxetine (Paxil, Paxil CR, Pexeva, Brisdelle) | Oral tablet, immediate-release (Paxil, Pexeva, generic): 10 mg, 20 mg, 30 mg, 40 mg Oral capsule (Brisdelle, generic): 7.5 mg Oral tablet, controlled release (Paxil CR): 12.5 mg, 25 mg, 37.5 mg Oral suspension (Paxil, generic): 10mg/5mL | •Dry mouth •Headache •Sedation •Drowsiness •Ejaculation difficulty | •Cannot be used with MAOIs or within 14 days of stopping one •Cannot be used with pimozide or thioridazine •Paroxetine should not be used in pregnant women |
Fluvoxamine | Oral tablet, immediate-release : 25 mg, 50 mg, 100 mg Oral capsule, extended-release: 100 mg, 150 mg | •Nausea •Headache •Dry mouth •Diarrhea •Dizziness •Abnormal physical weakness or lack of energy | •Cannot be used with MAOIs or within 14 days of stopping one |
*All medications can cause side effects which can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and understand the potential side effects and benefits of any medication.
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SNRIs as Zoloft Alternatives
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are another class of antidepressants that can be used instead of Zoloft. They work similarly to SSRIs, leaving more natural chemicals available for the body to use to manage symptoms. The difference is that instead of just working on serotonin like an SSRI, SNRIs work with both serotonin and norepinephrine.
Like SSRIs, SNRIs are associated with less serious side effects. Compared with SSRIs, the SNRI class tends to cause more nausea, insomnia, dry mouth, and rarely elevated blood pressure.9
Medications belonging to this class include Cymbalta (duloxetine), Effexor (Venlafaxine), Pristiq (desvenlafaxine), and Fetzima (levomilnacipran). All of these medications can be used for depression, with Effexor having the added indications of generalized anxiety disorder, panic disorder, and social phobia. Cymbalta is unique in that it can also be used to treat anxiety and nerve or pain conditions like fibromyalgia and diabetic peripheral neuropathy.
Pristiq was shown to be comparable to Effexor and SSRIs, and Fetzima is known to be more potent and may be a possible treatment option for those with major depressive disorder who cannot tolerate other SNRIs.10
Atypical Antidepressants as Zoloft Alternatives
Atypical antidepressants are medications that do not formally fit into other categories, often working in multiple ways to help manage conditions. These medications include Wellbutrin (bupropion) and Remeron (mirtazapine). Wellbutrin works similarly to SSRIs and SNRIs, preventing the reuptake and diminished action of chemicals, specifically dopamine and norepinephrine. Remeron blocks certain receptors, leading to an increase in norepinephrine and dopamine.
They may be prescribed as alternatives to SSRIs and SNRIs. Atypicals may also be used with consideration of other effects they have on patients, such as Wellbutrin giving patients more energy and Remeron helping a patient gain weight or sleep.
Wellbutrin has the benefit of having little to no sexual dysfunction or weight gain associated with it, but it cannot be used in patients with eating disorders. It may also cause more side effects like insomnia and anxiety. Remeron causes side effects like weight gain and drowsiness.10
TCAs & MAOIs as Zoloft Alternatives
Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) were some of the first antidepressants to become available as treatments. They fell out of favor due to their larger potential for side effects, but they still have a place in mental health treatment today. Often, these medications are used when the newer antidepressants are contraindicated, ineffective, or intolerable for a patient.
MAOIs use has dietary restrictions where patients need to limit the amount of high-tyramine foods they consume, which can be found in fermented foods. There is potential for a severe increase in blood pressure due to MAOIs blocking the breakdown of tyramine.
MAOIs may also cause sexual dysfunction and carry a warning of serotonin syndrome, which is a life-threatening condition. TCAs are known to have dehydrating effects, causing side effects like urinary retention, dry mouth, and constipation. TCAs also carry a risk for seizures, a change of heart rhythm, and a form of low blood pressure that happens when standing up from lying or sitting.10,11
How to Get a Prescription for Alternatives to Zoloft
Antidepressants are available by prescription only. They can be prescribed by licensed physicians or by other health care providers who are authorized under their supervision to prescribe antidepressants. To get a prescription for antidepressants, your physician will conduct an exam to assess your symptoms and may have you do lab work to rule out underlying conditions or contraindications. Once on the medication, your dosing may change depending on your response to it.
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Over-the-Counter Alternatives to Zoloft
A common question about Zoloft alternatives is about using supplements or herbal remedies as treatments. They are largely accessible and may appeal to those who are looking for natural alternatives to Zoloft. While limited in evidence for their efficacy and safety, they may hold benefits for some. However, some herbals and supplements may interact with medications, potentially resulting in less effective treatments or unintended side effects. If you are interested in starting an over-the-counter supplement, consult your doctor or pharmacist.
Over-the-counter Zoloft alternatives include:*
St John’s Wort
In some studies, St John’s wort has been found to reduce depressive symptoms in those with mild-to-moderate depression with comparable efficacy and safety compared to SSRIs. There is limited evidence of the efficacy and safety of St John’s wort in depression, and if it would be beneficial for patients with severe depression, high suicidality, or suicide risk.12,13 This herbal is also well-known for interacting with many medications, potentially causing medications to not work as intended and causing side effects.14
Vitamin B
Vitamin B is required in many functions in the body, and deficiencies may result in a multitude of problems, including brain functioning, anemia, and depression symptoms.15 There is no concrete evidence showing that Vitamin B12 has positive effects on depression, but lower levels of B12 have been associated with a higher risk of developing depression.
Omega-3 Fatty Acids
It is suggested that omega-3 fatty acids may offer some benefit to those with depression. More studies are needed to determine how effective Omega-3 really is, but it is thought to help with inflammation as well as improve depressive symptoms.16
5-HTP
5-Hydroxytryptophan (5-HTP) is an amino acid that can be converted to serotonin in the body and is produced from the seeds of a plant.17 It is possibly effective for depression in some people, but caution should be had as it can interact with medications like SSRIs, sedatives, and opioids. These interactions can be serious and may require medical intervention.
SAMe
S-adenosylmethionine, SAMe, is a naturally occurring chemical found in the body. There have been studies on SAMe in depression that showed evidence of benefit, but the evidence is not conclusive as these were not quality studies. This substance may interact with some medication or dietary supplements, and may not be safe for people with bipolar disorder.18
*Dietary supplements (including vitamins, supplements, herbs, and natural medicines) are not regulated the same way as medications by the FDA. Before being sold to the public, these products do not have the same clinical trials to determine their safety and efficacy. You should consult your doctor or pharmacist before starting any new dietary supplement.
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The Role of Therapy & Lifestyle Changes in Managing Depression
Medications are not the only methods for treating depression. Psychotherapy and lifestyle modifications are important methods for improving symptoms of depression. These methods alone, and especially in combination with medications, are useful in helping you manage your emotions, change your way of thinking, and teach you how to make choices that are helpful for your situation. Together with lifestyle changes, you may be able to increase the likelihood of improved depressive symptoms.
Effective therapy options for depression include:19
Psychodynamic Therapy
Psychodynamic therapy focuses on your unconscious thoughts and early experiences and helps you understand current challenges, improve self-awareness, and support you in developing skills to function. The goal of psychodynamic therapy in depression is to help you develop a greater tolerance for uncomfortable feelings and to build a reliance on yourself, rather than others, to handle negative emotions or feel good.
Cognitive Behavioral Therapy (CBT)
CBT is an evidence-based form of psychotherapy that is helpful for those with depression. It is a goal-based therapy that helps you change unhelpful and unhealthy habits. CBT is used to give you skills to help you manage your thoughts and behaviors.
Dialectical Behavior Therapy (DBT)
DBT for depression helps patients develop skills to support themselves, identifying what is and isn’t within their control. DBT focuses on helping people accept the realities of their lives and teaching them to change their lives and unhelpful behaviors.
Supportive Therapy
This therapy is meant to provide support, helping the patient to explore and understand their current situations by providing empathy and supportive listening. It focuses on helping a person to cope with life’s stressors and enable them to make choices in regard to these situations. In depression, supportive therapy can help you better understand the challenges you face and empower you to handle them better.
Interpersonal Psychotherapy (IPT)
Interpersonal therapy (IPT) aims to improve your relationship with others by teaching you strategies to effectively communicate your emotions and needs. With depression, your social and emotional functioning are evaluated by a therapist, and they eventually work with you to identify strategies to help improve problem areas and improve your relationships, all with the goal of reducing depressive symptoms.
Important lifestyle changes for managing depression include:20
- Diet: People with mental health conditions should try to have balanced diets, limiting the amount of refined sugar they consume. Diets high in refined sugars are associated with worsening symptoms.
- Exercise: Being physically active can help to reduce symptoms of anxiety and depression, and increase overall mood. Some medications can be associated with side effects like weight gain, which regular exercise can help to manage.
- Avoid substance abuse and smoking: Drugs and alcohol are often used to cope with symptoms of mental conditions like depression, but these substances can actually worsen symptoms and potentially create more problems. For example, taking antidepressants with certain illicit drugs can increase your risk of a potentially life-threatening condition called Serotonin Syndrome. Recreational drugs should be avoided, and alcohol should be limited.
- Get a good night’s sleep: Sleep habits and mental health conditions are often connected, which can become a cycle if one of them is not taken care of. Practicing good sleep hygiene can help to keep a more consistent sleep schedule.
- Have a support system: Having a mental condition can be isolating and overwhelming. Having a reliable support system to help provide relief and a sense of community during trying times.
Questions to Ask Your Healthcare Team About Zoloft Alternatives
When starting a new medication, you should consult your doctor and pharmacist to ensure your therapy works as intended. Before obtaining a prescription, attend your appointment with a list of questions to ask your doctor or psychiatrist. Be sure to let your doctors and pharmacist know if you change or start any medications.
Questions to ask your care team about Zoloft alternatives include:
- Is it safe to take antidepressants with my other medications?
- Am I at risk for side effects from antidepressants or supplements if I am already taking other medications, such as anti-anxiety medication?
- What antidepressants should I consider for fewer side effects?
- Will my symptoms get better without medication?
- How long should I try an antidepressant before deciding it is not for me?
- How is this medication compared to Zoloft?
- How do natural remedies compare to Zoloft?
- Can I take natural remedies alongside my antidepressant?
- What lifestyle changes can I make to help manage my mood?
- What are signs that I should consider an alternative to my antidepressant?
In My Experience
Choosing Therapy strives to provide our readers with mental health content that is accurate and actionable. We have high standards for what can be cited within our articles. Acceptable sources include government agencies, universities and colleges, scholarly journals, industry and professional associations, and other high-integrity sources of mental health journalism. Learn more by reviewing our full editorial policy.
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Ferguson J. M. (2001). SSRI Antidepressant Medications: Adverse Effects and Tolerability. Primary care companion to the Journal of clinical psychiatry. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181155/
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Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK554406/
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ZOLOFT- sertraline hydrochloride solution, concentrate. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm -
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DailyMed. (2023). Paxil- paroxetine. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm
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DailyMed. (2023). FLUVOXAMINE MALEATE capsule, extended-release. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm
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Sansone, R. A., & Sansone, L. A. (2014). Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innovations in clinical neuroscience. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008300/
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Santarsieri, D., & Schwartz, T. L. (2015). Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs in context. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630974/
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Sheffler ZM, Patel P, Abdijadid S. Antidepressants. [Updated 2023]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK538182/
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Ng, Q. X., Venkatanarayanan, N., & Ho, C. Y. (2017). Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. Journal of affective disorders. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28064110/
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Zhao, X., Zhang, H., Wu, Y., & Yu, C. (2023). The efficacy and safety of St. John’s wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials. Advances in clinical and experimental medicine: official organ Wroclaw Medical University. Retrieved from https://pubmed.ncbi.nlm.nih.gov/36226689/
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Nicolussi, S., Drewe, J., Butterweck, V., & Meyer Zu Schwabedissen, H. E. (2020). Clinical relevance of St. John’s wort drug interactions revisited. British journal of pharmacology. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31742659/
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Sangle, P., Sandhu, O., Aftab, Z., Anthony, A. T., & Khan, S. (2020). Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression. Cureus.
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Liao, Y., Xie, B., Zhang, H., He, Q., Guo, L., Subramanieapillai, M., Fan, B., Lu, C., & McIntyre, R. S. (2019). Efficacy of omega-3 PUFAs in depression: A meta-analysis. Translational psychiatry. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31383846/
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S-Adenosyl-L-Methionine (SAME): In depth. (2017). NCCIH. Retrieved from https://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth
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