TL;DR

  • Antidepressants work only slightly better than placebo, with strong evidence of publication bias.
  • Side effects and risks (including violence and suicide) are documented.
  • Inflammation, stress, and nutrient deficiencies play major roles in depression and anxiety.
  • SSRIs may worsen the microbiome, fueling inflammation.
  • Nutrients like thiamin, vitamin D, omega-3s, magnesium, and trace lithium show promise.
  • Lifestyle changes and anti-inflammatory nutrition strongly influence outcomes.

Antidepressant Effectiveness

Studies show antidepressants are not as effective as widely believed.

  • 40–60 out of 100 patients report improvement in 6–8 weeks, according to the British Medical Journal【1】.
  • Even these numbers may be inflated due to publication bias. A review in Psychotherapy and Psychosomatics noted that antidepressants are only marginally better than placebo【2】.

Despite limited effectiveness, 17% of Americans take antidepressants, generating $17.4 billion annually.

Reported side effects include:

  • Headache, nausea, dry mouth, drowsiness, insomnia, weight gain
  • Agitation, rash, diarrhea, restlessness, sexual dysfunction

In 2004, studies linked SSRIs to teen suicide, leading to an FDA black box warning.

Research Linking SSRIs to Violence

Since SSRIs entered the market in 1987 (starting with Prozac), rates of violence and mass shootings have surged. Research shows:

  • Antidepressants double the risk of events leading to suicide and violence in healthy adults【4】.
  • A Swedish registry study linked SSRIs with higher violent crime rates【3】.

Industry defenders point out that 97% of patients in the study did not show violent behavior. But with 35 million Americans on SSRIs, that still leaves over 1 million at risk.

Withdrawal Risks

Stopping SSRIs abruptly can trigger severe withdrawal:

  • Flu-like symptoms, fatigue, headaches, sweating
  • Nightmares, nausea, dizziness, “brain zaps” (shock-like sensations)
  • Irritability, agitation, aggression, anxiety

Onset: 2–4 days after stopping
Duration: 1–3 weeks (sometimes longer, peaking in the first week)

Inflammation and the Brain

Inflammation is a major factor in mental health.

  • High CRP = poorer antidepressant response and more cognitive problems【5】.
  • People with depression and anxiety have more inflammatory chemicals circulating in the blood (like CRP, IL-6, and TNF-α)【6】.
  • PTSD patients show elevated inflammatory markers【10】.

Inflammation disrupts serotonin production, and makes quinolinic acid (a neurotoxin) instead. This is linked to Alzheimer’s, autism, and suicide【11】【12】.

SSRIs may worsen inflammation via the microbiome:

“SSRIs affect enteric neurons and have antimicrobial properties, disrupting microbial balance.” (Front Psychiatry, 2021)【13】

Stress and the HPA Axis

Chronic stress causes the body to make excess cortisol.【14】【15】. This leads to:

  • Anxiety
  • Inflammation
  • Sympathetic nervous system overdrive

Stress is a long-established trigger for anxiety and depression【16–20】.

Nutrient Factors in Mental Health

Thiamin

  • Deficiency is under-diagnosed but common.
  • Found in 30% of psychiatric patients【21】.
  • Supplementation improves mood, memory, and anxiety【22】【23】.

Lithium Orotate

  • Low-dose trace lithium, not the high-dose drug lithium carbonate.
  • Shown to reduce aggression, suicide, and violence【24】【25】.
  • Supports neuroprotection (Bcl-2 proteins)【26】.
  • Areas with lithium in drinking water show lower violence and suicide rates.

Other Nutrients

  • B vitamins improve depression【27】.
  • Vitamin D deficiency is linked to depression【28】【29】.
  • DHA (omega-3) deficits occur in depressed patients【30】.
  • Exercise often outperforms medication【31】【32】.
  • Magnesium improves mood【33】【34】.

Practical Options (Educational Only)

You don’t treat depression—you support the patient with tools to lower inflammation, balance stress, and supply missing nutrients.

Suggestions from clinical practice:

  • Anti-Inflammation Diet – reduces the single biggest driver of depression/anxiety. Try the Roadmap to Health.
  • Daily Stress Formula (Pure Encapsulations) – herbs + vitamins to reduce cortisol.
  • BenfoMax (200 mg thiamin) – addresses deficiency-linked depression.
  • Lithium Orotate (1 mg) – mood stabilizing trace mineral.

If results are limited, deeper testing (stool analysis, thyroid, food sensitivities) may help. Work with doctors trained in natural healthcare for personalized guidance.

FAQs

Q: Do antidepressants really work?
A: Evidence shows they are only marginally better than placebo, with high risk of publication bias.

Q: Can antidepressants cause violence?
A: Some studies link SSRIs with higher violent crime and suicide-related behaviors in some patients.

Q: Why is inflammation so important?
A: Inflammation disrupts serotonin metabolism, fuels neurotoxins like quinolinic acid, and is consistently found elevated in depression and anxiety.

Q: What nutrients are most linked to mental health?
A: Thiamin, vitamin D, B vitamins, omega-3s (DHA), magnesium, and trace lithium show strong associations.

Q: Should I stop my antidepressant?
A: No. SSRIs can cause severe withdrawal. Only stop or adjust medication with a prescribing clinician.

References

Footnotes

  1. (Br J Psychiatry. 2011 Jan;198(1):11-6, sup 1) Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis
  2. Psychother Psychosom (2010) 79 (5): 267–279. Efficacy and Effectiveness of Antidepressants: Current Status of Research
  3. Eur Neuropsychopharmacol. 2020 Jul; 36: 1–9. Associations between selective serotonin reuptake inhibitors and violent crime in adolescents, young, and older adults – a Swedish register-based study
  4. J R Soc Med. 2016 Oct;109(10):381-392 Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers
  5. Brain Behav Immun. 2012 Jan;26(1):90-5 Treatment response and cognitive impairment in major depression: association with C-reactive protein
  6. Psychoneuroendocrinology 2013 Sep; 38(9): 1573-85 Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA)
  7. Brain Behav Immun. 2015 Jul;47:193-200 Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation
  8. Anxiety in relation to inflammation and coagulation markers, among healthy adults: the ATTICA study Atherosclerosis. 2006 Apr;185(2):320-6.
  9. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond Neuropsychopharmacology. 2017 Jan;42(1):254-270.
  10. Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression Lancet Psychiatry. 2015 Nov;2(11):1002-12
  11. Redox Rep. 2002;7(4):199-206. Implications of the kynurenine pathway and quinolinic acid in Alzheimer’s disease
  12. J Alzheimers Dis. 2018;62(2):523-547 Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines
  13. Front Psychiatry. 2021; 12: 682868. Serotonin Reuptake Inhibitors and the Gut Microbiome: Significance of the Gut Microbiome in Relation to Mechanism of Action, Treatment Response, Side Effects, and Tachyphylaxis
  14. Prim Care Companion J Clin Psychiatry. 2001; 3(4): 151–155. The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians
  15. J Affect Disord. 2018 Jun;233:45-67. Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review
  16. Patriquin M.A., Mathew S.J. The Neurobiological Mechanisms of Generalized Anxiety Disorder and Chronic Stress. Chronic. Stress (Thousand Oaks) 2017;1
  17. Lin E., Tsai S.J. Gene-Environment Interactions and Role of Epigenetics in Anxiety Disorders. Adv. Exp. Med. Biol. 2020;1191:93–102.
  18. Conway C.C., Rutter L.A., Brown T.A. Chronic environmental stress and the temporal course of depression and panic disorder: A trait-state-occasion modeling approach. J. Abnorm. Psychol. 2016;125:53–63.
  19. Wade S.L., Monroe S.M., Michelson L.K. Chronic life stress and treatment outcome in agoraphobia with panic attacks. Am. J. Psychiatry. 1993;150:1491–1495.
  20. Patriquin M.A., Mathew S.J. The Neurobiological Mechanisms of Generalized Anxiety Disorder and Chronic Stress. Chronic. Stress (Thousand Oaks) 2017;1
  21. Thiamine, riboflavin and pyridoxine deficiency in psychiatric in-patients. Br. J. Psychiatry 1982, 141, 271–272.
  22. Adjuvant thiamine improved standard treatment in patients with major depressive disorder: Results from a randomized, double-blind, and placebo-controlled clinical trial. Eur. Arch. Psychiatry Clin. Neurosci. 2016, 266, 695–702.
  23. The impact of thiamine treatment on generalized anxiety disorder. Int. J. Clin. Med. 2011, 2, 439.
  24. Biol Trace Elem Res. 1990 May;25(2):105-13 Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions
  25. J Am Coll Nutr. 2002;21(1):14–21. Lithium: occurrence, dietary intakes, nutritional essentiality.
  26. J Clin Psychiatry 2000;61(Suppl 9):82-96. 18. Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness
  27. Psychosomatic Medicine October 2010 72:763-768 Dietary folate, riboflavin, vitamin B-6, and vitamin B-12 and depressive symptoms in early adolescence: the Ryukyus Child Health Study
  28. Asia Pac J Clin Nutr. 2019;28(4):689-694. Vitamin D and depression: mechanisms, determination and application
  29. British Journal of Psychiatry (Epublished ahead of print, July 12, 2012)
  30. Biological Psychiatry (1 July 2007; Volume 62, Issue 1, Pages 17-24 Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder
  31. Am J Prev Med. 2005 Jan;28(1):1-8 Exercise treatment for depression: efficacy and dose response
  32. J Affect Disord. 2017 Feb;209:188-194 Exercise is an effective treatment for positive valence symptoms in major depression
  33. PLoS One. 2017 Jun 27;12(6):e0180067. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial
  34. Stress Health. 2021 Dec;37(5):1000-1009. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial