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Trintellix Alternatives (vortioxetine)

Last Updated on January 10, 2024 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Michael Loes MD

The difference in cost between the prescription antidepressant Trintellix© vs natural Trintellix alternatives is mind-boggling, especially as inflation rages across the world. But for those whose focus rests on actual healing, the differences may be even more profound. Read on for strategic Trintellix alternatives for treating depression, loss of interest in life, and other manifestations without the troubling side effects associated with SSRIs.

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What is Trintellix?

Trintellix is a pricey SSRI (serotonergic) medication the FDA approved in 2013 for treating major depression in adults. Trintellix runs roughly $450 a month, compared to under $10/month for comparative SSRI products like fluoxetine (Prozac©) or sertraline (Zoloft©).2 But there may be other costs to consider.

Perhaps to help justify the price tag, the drugmaker attempted to prove the drug was not only effective in reducing depressive symptoms better than its cohort of other SSRIs but claimed that Trintellix might also improve cognitive function or “cloudy thinking.” Clinical trials failed to prove the case and drug regulators denied the claim.34 As a result, Trintellix is currently marketed as an “alternative” SSRI in the case of “treatment resistive depression,” as a drug of last resort rather than a first-line treatment.5

The Trintellix label discloses the same black box warning as all other antidepressants of increasing suicidality, which is most prevalent in the 24 and under age range. Hence, it only gained approval for ages 25 and up.1 Some experts in the field of mental health consider antidepressants, in general, do not make people happier, and the efficacy of these drugs remains unproven.14 Additionally, more information about Trintellix’s adverse effects will be presented below.

Natural Alternatives to Trintellix

Natural Alternatives to Trintellix include:
  • natural holistic alternatives to trintellixCBT and other forms of counseling 8
  • Lifestyle changes, replacing toxic habits with beneficial activities 31,38
  • Exercise 19-21
  • Diet modification 17,31,37
  • Bright light therapy 35
  • Neurotoxin removal 32,33
  • Support for healthy microbiome function through diet and supplementation 36
  • Orthomolecular medicine, replenishing vitamins, minerals, and use of herbal proven remedies 4,6,17,25-30,37

There are many other natural alternatives to Trintellix to consider either before starting a prescription, or that can be useful as part of a carefully monitored program to wean off Trintellix as comfortably as possible. More information follows on these subjects.

Why Consider Trintellix Alternatives?

The cost of treatment, the efficacy of treatment, and potential drug-induced side effects are three major issues that deserve careful consideration. Aside from the cost-benefit of Trintellix alternatives, Trintellix alternative treatments may be more desirable in that holistic or drug-free therapies do not induce devastating side effects that are associated with prescription drugs. One need not be forced into a trade-off of overall health and wellness for a modicum of relief (if any) in treating lingering depression.

Clinical trials on many Trintellix alternative treatments show at least as great if not better results than drug-based treatment outcomes. Herbal remedies such as St. John’s Wort, hypericum, passionflower, and many other non-pharmacological strategies have shown great promise in clinical trials. Further information on diet and supplementation options to consider is detailed below.

Trintellix Side Effects

Reported Trintellix side effects on the drug insert include:
  • trintellix black box warningSuicide risk:  most prominently in children and young adults to age 24.
  • Clinical worsening:  this category includes symptoms such as panic attacks, insomnia, hostility, irritability, anxiety, akathisia, impulsivity, aggressiveness, hypomania, and mania.
  • Worsened depression:  where treatment emergent depression occurs or worsens the prescribing information indicates the drug should possibly be discontinued.
  • Serotonin syndrome:  a potentially fatal reaction featuring high fever, disorientation, profuse sweating, coma, and unconsciousness. Trintellix is often used as an alternative medication where other antidepressants were without efficacy, so switching to Trintellix from another medication may present elevated risks of too much serotonin in the system, resulting in serotonin syndrome, and must be carefully monitored.
  • Gastrointestinal bleeding:  can lead to life-threatening hemorrhages.
  • Treatment-emergent hypomania (lasts for up to 4 days) or mania (lasts for 7 days or more).
  • Angle-closure glaucoma:  a condition where fluids around the iris are not able to drain properly, causing pressure in the eyes, blurred vision, severe head and eye pain, and sudden blindness. Angle-closure glaucoma requires immediate medical attention.
  • Angioedema:  a reaction to medication that causes hive-like swelling under the skin and mucous membranes. If breathing becomes constricted, the condition may become life-threatening.

Can Natural Alternatives to Trintellix Help Avoid Side Effects?

Research has shown that non-pharmacological treatments for depression can be very effective, with the added benefit of not producing the adverse effects associated with antidepressants. According to research published in the Australian and New Zealand Journal of Psychiatry, 75% of prescriptions for antidepressant medications come from GPs, rather than mental health practitioners.24

While GPs do an excellent job in diagnosing and treating physical infections, injuries, broken bones, and other physical ailments, why should anyone expect them to be mental health experts too? These physicians are not trained in mental health. Could this be why the majority of patients coming to a doctor for help with depression receive a quick prescription, and no information is given about alternatives to Trintellix? One would be well-advised to consult with professionals who are adequately informed about both drugs AND drug-free alternatives to Trintellix. And why do so many patients tell us that they were never informed about possible side effects of the medications they were prescribed? Could it be because the doctors themselves were never informed in medical school? 4,39

Therapy as an Alternative to Trintellix

Therapy is never a one-size-fits-all affair. Despite feeling perhaps fragile and unsure about making correct treatment choices, one can take time to actually interview a number of potential therapists before embarking on a course of treatment, to establish confidence or lack thereof, and assess if they are a good fit for you.

An interesting study published in the Journal of Psychotherapy Practice and Research found that, given the opportunity to choose between therapists, 75% of patients did not ultimately choose the first available therapist.7

While we tend to think of counseling in a one-on-one setting, take time to consider additional modes of therapy as there are quite a number of approaches available. Here are some examples:

  • Group sessions vs private sessions
  • Virtual therapy accessed on-line
  • Cognitive-behavioral counseling (CBT) 8
  • Trauma and grief counseling
  • Vocational-related counseling such as stress management or exploring more satisfying career choices
  • Therapy designed for seniors, single parents, family counseling, or other personal interests either in peer-support-group or private settings

Dietary Changes and Supplements as Alternatives to Trintellix

essential nutrition as alternatives to trintellixIn the middle of a mental health crisis, it may not be the first thing that comes to mind to modify the diet. Root causes for mental symptoms are often overlooked and not investigated at all. A diagnosis or label is not synonymous with a solution and may feel more like a dead end.

However, a deficiency in certain vitamins confirmed by testing has been frequently correlated with patients suffering symptoms of depression, insomnia, and other unwanted symptoms. Replenishing vitamins and minerals has been found highly efficacious as a treatment option for depression (and other symptoms) and is a much-researched alternative to Trintellix. Drugs may simply mask symptoms and are not designed to fix the root cause. Here are some examples of dietary changes including supplementation that may provide effective alternatives to Trintellix or other antidepressants:

  • Supplements shown in clinical trials to help relieve depression:  St John’s Wort, hypericum, saffron extracts, passionflower, quercetin, B vitamins, vitamin C, vitamin D, magnesium, Omega-3 fatty acids, tryptophan, zinc, probiotics.4,6,17,25-30
  • Improve diet:  eat organic where possible to avoid toxic pesticides, choose unprocessed foods without the neurotoxic chemicals used in commercial processing, consume food-based probiotics like sauerkraut or yogurt, avoid sugars and refined carbs that spike blood sugar resulting in fatigue and low mood, incorporate daily intake of fresh fruits and vegetables — fruits and vegetables are rich sources of vital nutrients such as magnesium, zinc, calcium, folic acid, potassium, and many others.17,31

Lifestyle Changes as an Alternative to Trintellix

trintellix alternative lifestyle changesChange can be difficult. What we decide one day would be helpful, often gets discarded because of exhaustion, fatigue, self-sabotage, lack of support, or lack of self-discipline in carrying through on our best intentions. Whether one uses the services of a lifestyle coach, or simply begins to thoughtfully re-design one’s lifestyle and day-to-day activities, there are many potential benefits to be had in making such changes. You may feel overwhelmed today. Tomorrow, can you be a bit more proactive? Consider these examples:

  • Regular, good-quality sleep. Remove blue light and electronics from the bedroom, keep the bedroom well ventilated, and use dust-free pillows and a comfortable mattress. Avoid caffeine some hours before retiring. Explore natural and herbal sleep remedies such as 5THP, melatonin, magnolia, rosemary, ginseng, and angelica root. Many of the following interventions will also have positive spill-over impacts on the quality of sleep, and this can greatly benefit one’s mental health.15,16
  • Strive for eating healthy foods and don’t skip meals. Some examples of dietary recommendations are given in more detail in the earlier section entitled “Dietary Changes and Supplements as Alternatives to Trintellix.”
  • Dissolve or at least distance yourself from toxic relationships.10
  • Make new friends, and spend more time with people you like.9
  • If you dislike your job, consider a career change.11
  • If financial stress is on your list, seek financial advice and begin a plan to work it out. 11
  • Volunteer activities: helping others is considered by some to be life’s “secret sauce” that leads to authentic happiness, profound satisfaction, and even a longer lifespan.18
  • Daily or regular exercise — outdoor walks, swimming, Tai Chi, Qi gong, yoga, dance! 19-21
  • If you dislike where you live, consider moving.22
  • Check for possible toxic exposures: mercury amalgams, mycotoxins from mold, off-gassing carpets and furniture, toxic cookware, chemicals in cleaning products or personal hygiene items, etc. in the home or workplace and remove the source, or in the case of irreparable exposure situations, such as living next to a chemical plant, consider relocating if there is no other option.32,33
  • Religion and spirituality have shown practical, positive effects on mental health in clinical trials.12
  • Pick an enjoyable hobby, art project, or resurrect an activity you liked in the past.23
  • Dedicate some time to listening to music you love — neuroscience claims it can be dramatically transformational.13

Even small changes can reap great rewards, so start as small as you like, and remember that self-compassion is also highly therapeutic.8 Realize there is no perfect person or perfect life anywhere on earth, and we all have experienced failures somewhere in our lives. You don’t have to ignore or succumb to the things that you wish to change but find difficult to overcome. Take a moment to consider if it’s possible to be less self-critical and demanding of yourself. Could you be kinder to yourself, just as you would wish others to be kind to you? And practice self-compassion just as much as you would also wish to be kind and benevolent to others?

Effective Trintellix Alternatives at Alternative to Meds Center

holistic treatment substance abuse sedona drug rehabAlternatives to Trintellix have been combined into a multi-faceted program, using therapies such as those outlined plus many more. We apply clinically proven techniques to reduce stress, worry, depression, insomnia, and anxiety, while at the same time offering safe and comfortable drug withdrawal where needed.

Alternative to Meds is a nurturing, pristine, and compassionate facility nestled in the majestic Red Rocks in Sedona Arizona. Your inquiry is welcome and we will be happy to give you additional information on the details of our holistic programs as well as insurance coverage and any other questions you or your loved one may have. Contact us today for more information on alternatives to Trintellix and how these principles may change your life and help you finally recover your natural mental health without prescription drugs.


1. FDA drug label Trintellix (vortixetine tablets) Initial US approval 2013 [cited 2022 June 14]

2. Trintellix Drugmaker’s Price Information [cited 2022 June 14]

3. Mahableshwarkar AR, Jacobsen PL, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015 Jun;232(12):2061-70. doi: 10.1007/s00213-014-3839-0. Epub 2015 Jan 11. PMID: 25575488; PMCID: PMC4432084. [cited 2022 June 14]

4. Josey ES, Tackett RL. St. John’s wort: a new alternative for depression? Int J Clin Pharmacol Ther. 1999 Mar;37(3):111-9. PMID: 10190758. [cited 2022 June 14]

5. Brignone M, Diamand F, Painchault C, Takyar S. Efficacy and tolerability of switching therapy to vortioxetine versus other antidepressants in patients with major depressive disorder. Curr Med Res Opin. 2016;32(2):351-66. doi: 10.1185/03007995.2015.1128404. PMID: 26637048. [cited 2022 June 14]

6. Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer’s disease. J Nutr Biochem. 2009 Apr;20(4):269-75. doi: 10.1016/j.jnutbio.2008.03.002. Epub 2008 Jul 7. PMID: 18602817; PMCID: PMC2737260. [cited 2022 June 14]

7. Alexander LB, Barber JP, Luborsky L, Crits-Christoph P, Auerbach A. On what bases do patients choose their therapists?J Psychother Pract Res. 1993;2(2):135-146. [cited 2022 June 14]

8. Neff KD. The Role of Self-Compassion in Development: A Healthier Way to Relate to Oneself. Hum Dev. 2009;52(4):211-214. doi:10.1159/000215071 [cited 2022 June 14]

9. Cacioppo JT, Cacioppo S. Social Relationships and Health: The Toxic Effects of Perceived Social IsolationSoc Personal Psychol Compass. 2014;8(2):58-72. doi:10.1111/spc3.12087 [cited 2022 June 14]

10. Markey CN, Markey PM. Personality, relationships, and health. J Pers. 2014 Dec;82(6):467-71. doi: 10.1111/jopy.12080. Epub 2014 Feb 8. PMID: 24299020. [cited 2022 June 14]

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12. Gonçalves JP, Lucchetti G, Menezes PR, Vallada H. Religious and spiritual interventions in mental health care: a systematic review and meta-analysis of randomized controlled clinical trials. Psychol Med. 2015 Oct;45(14):2937-49. doi: 10.1017/S0033291715001166. Epub 2015 Jul 23. PMID: 26200715; PMCID: PMC4595860. [cited 2022 June 14]

13. Särkämö T, Soto D. Music listening after stroke: beneficial effects and potential neural mechanisms. Ann N Y Acad Sci. 2012 Apr;1252:266-81. doi: 10.1111/j.1749-6632.2011.06405.x. PMID: 22524369. [[cited 2022 June 14]

14. Ioannidis, J.P. Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?Philos Ethics Humanit Med 3, 14 (2008). [cited 2022 June 14]

15. Irish LA, Kline CE, Gunn HE, Buysse DJ, Hall MH. The role of sleep hygiene in promoting public health: A review of empirical evidenceSleep Med Rev. 2015;22:23-36. doi:10.1016/j.smrv.2014.10.001 [cited 2022 June 14]

16. Hu Z, Oh S, Ha TW, Hong JT, Oh KW [2018] Sleep-Aids Derived from Natural Products. Biomolecules and Therapeutics, 26(4), 343-349. [cited 2022 June 14]

17. Ljungberg T, Bondza E, Lethin C. Evidence of the Importance of Dietary Habits Regarding Depressive Symptoms and DepressionInt J Environ Res Public Health. 2020;17(5):1616. Published 2020 Mar 2. doi:10.3390/ijerph17051616 [cited 2022 June 14]

18. Musick MA, Wilson J. Volunteering and depression: the role of psychological and social resources in different age groups. Soc Sci Med. 2003 Jan;56(2):259-69. doi: 10.1016/s0277-9536(02)00025-4. PMID: 12473312. [cited 2022 June 14]

19. Wang F, Lee EK, Wu T, Benson H, Fricchione G, Wang W, Yeung AS. The effects of tai chi on depression, anxiety, and psychological well-being: a systematic review and meta-analysis. Int J Behav Med. 2014 Aug;21(4):605-17. doi: 10.1007/s12529-013-9351-9. PMID: 24078491. [cited 2022 June 14]

20. Peluso MA, Guerra de Andrade LH. Physical activity and mental health: the association between exercise and mood. Clinics (Sao Paulo). 2005 Feb;60(1):61-70. doi: 10.1590/s1807-59322005000100012. Epub 2005 Mar 1. PMID: 15838583. [cited 2022 June 14]

21. Schuch FB, Vancampfort D, Firth J, Rosenbaum S, Ward PB, Silva ES, Hallgren M, Ponce De Leon A, Dunn AL, Deslandes AC, Fleck MP, Carvalho AF, Stubbs B. Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies. Am J Psychiatry. 2018 Jul 1;175(7):631-648. doi: 10.1176/appi.ajp.2018.17111194. Epub 2018 Apr 25. PMID: 29690792. [cited 2022 June 14]

22. Purtle J, Nelson KL, Yang Y, Langellier B, Stankov I, Diez Roux AV. Urban-Rural Differences in Older Adult Depression: A Systematic Review and Meta-analysis of Comparative Studies. Am J Prev Med. 2019 Apr;56(4):603-613. doi: 10.1016/j.amepre.2018.11.008. Epub 2019 Feb 16. PMID: 30777704. [cited 2022 June 14]

23. Jensen A, Bonde LO. The use of arts interventions for mental health and wellbeing in health settings. Perspect Public Health. 2018 Jul;138(4):209-214. doi: 10.1177/1757913918772602. Epub 2018 Apr 30. Erratum in: Perspect Public Health. 2018 Sep;138(5):288. PMID: 29708025. [cited 2022 June 14]

24. McManus P, Mant A, Mitchell P, Britt H, Dudley J. Use of antidepressants by general practitioners and psychiatrists in Australia. Aust N Z J Psychiatry. 2003 Apr;37(2):184-9. doi: 10.1046/j.1440-1614.2003.01132.x. PMID: 12656957. [cited 2022 June 14]

25. Guan Y, Wang J, Wu X, Song L, Wang Y, Gong M, Li B. Quercetin reverses chronic unpredictable mild stress-induced depression-like behavior in vivo by involving nuclear factor-E2-related factor 2. Brain Res. 2021 Dec 1;1772:147661. doi: 10.1016/j.brainres.2021.147661. Epub 2021 Sep 13. PMID: 34529966. [cited 2022 June 14]

26. von Känel R, Fardad N, Steurer N, Horak N, Hindermann E, Fischer F, Gessler K. Vitamin D Deficiency and Depressive Symptomatology in Psychiatric Patients Hospitalized with a Current Depressive Episode: A Factor Analytic Study. PLoS One. 2015 Sep 23;10(9):e0138550. doi: 10.1371/journal.pone.0138550. PMID: 26397113; PMCID: PMC4580407. [cited 2022 June 14]

27. Szafrański T. Leki ziolowe w leczeniu depresji–aktualny stan wiedzy [Herbal remedies in depression–state of the art]. Psychiatr Pol. 2014 Jan-Feb;48(1):59-73. Polish. PMID: 24946435. [cited 2022 June 14]

28. Janda K, Wojtkowska K, Jakubczyk K, Antoniewicz J, Skonieczna-Żydecka K. Passiflora incarnata in Neuropsychiatric Disorders-A Systematic ReviewNutrients. 2020;12(12):3894. Published 2020 Dec 19. doi:10.3390/nu12123894 [cited 2022 June 14]

29. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. J Affect Disord. 2017 Mar 1;210:211-221. doi: 10.1016/j.jad.2016.12.048. Epub 2017 Jan 3. PMID: 28064110. [cited 2022 June 14]

30. Martínez-Cengotitabengoa M, González-Pinto A. Nutritional supplements in depressive disorders. Actas Esp Psiquiatr. 2017 Sep;45(Supplement):8-15. Epub 2017 Sep 1. PMID: 29171639. [cited 2022 June 14]

31. Samadian F, Dalili N, Jamalian A. Lifestyle Modifications to Prevent and Control Hypertension. Iran J Kidney Dis. 2016 Sep;10(5):237-263. PMID: 27721223. [cited 2022 June 14]

32. Genuis SJ. Toxic causes of mental illness are overlooked. Neurotoxicology. 2008 Nov;29(6):1147-9. doi: 10.1016/j.neuro.2008.06.005. Epub 2008 Jun 24. PMID: 18621076. [cited 2022 June 14]

33. Genuis SJ. Toxicant exposure and mental health–individual, social, and public health considerations. J Forensic Sci. 2009 Mar;54(2):474-7. doi: 10.1111/j.1556-4029.2008.00973.x. Epub 2009 Jan 31. PMID: 19187449. [cited 2022 June 14]

34. FDA Briefing Document Supplemental Drug Approval Vortioxetine for reatment of Cognitive Dysfunction in Major Depression Disorder published Feb 3 2016 [cited 2022 June 14]

35. Campbell PD, Miller AM, Woesner ME. Bright Light Therapy: Seasonal Affective Disorder and BeyondEinstein J Biol Med. 2017;32:E13-E25. [cited 2022 June 14]

36. Osadchiy V, Martin CR, Mayer EA. The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications. Clin Gastroenterol Hepatol. 2019 Jan;17(2):322-332. doi: 10.1016/j.cgh.2018.10.002. Epub 2018 Oct 4. PMID: 30292888; PMCID: PMC6999848. [cited 2022 June 14]

37. Wang J, Um P, Dickerman BA, Liu J. Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications. Nutrients. 2018 May 9;10(5):584. doi: 10.3390/nu10050584. PMID: 29747386; PMCID: PMC5986464. [cited 2022 June 14]

38. Yang SY, Fu SH, Chen KL, Hsieh PL, Lin PH. Relationships between depression, health‑related behaviors, and internet addiction in female junior college students. PLoS One. 2019 Aug 9;14(8):e0220784. doi: 10.1371/journal.pone.0220784. PMID: 31398212; PMCID: PMC6688785. [cited 2023 June 5]

39. Kerwick S, Jones R, Mann A, Goldberg D. Mental health care training priorities in general practice. Br J Gen Pract. 1997 Apr;47(417):225-7. PMID: 9196965; PMCID: PMC1312947. [cited 2023 June 5]

Originally Published April 22, 2022 by Diane Ridaeus

This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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Trintellix Alternatives (vortioxetine)
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Nothing on this Website is intended to be taken as medical advice. The information provided on the website is intended to encourage, not replace, direct patient-health professional relationships. Always consult with your doctor before altering your medications. Adding nutritional supplements may alter the effect of medication. Any medication changes should be done only after proper evaluation and under medical supervision.

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