Recommendations

Supplements

Below is a summary of supplements discussed as adjuncts in psychiatric practice, along with the current evidence. Their effects are generally small to moderate, and none of them replaces treatment.

This list is for information only. Use the supplements listed here ONLY if your doctor has specifically recommended them for you. They can interact with your medication; do not start them on your own and do not stop your current treatment.

  • 1) Saffron

    Note: Do not use if there is a possibility that you are pregnant.

    A meta-analysis incorporating 34 randomized controlled trials and using GRADE to assess the evidence reports that saffron significantly reduces depression scale scores compared with placebo (Mahmoudi et al., 2026). A meta-analysis of 8 trials directly comparing saffron with SSRIs found no significant difference between the two groups, with fewer adverse effects in the saffron group (Shafiee et al., 2025) — however, these trials were small and short-term; they are insufficient to conclude that saffron can replace SSRIs.

    Systematic reviews show that saffron significantly reduces anxiety scores compared with placebo (Marx et al., 2019).

    Studies have reported mild to moderate improvements in sleep quality and insomnia scores (PSQI, ISI) (Lian et al., 2022).

  • 2) NAC (N-acetylcysteine)

    Meta-reviews have identified it as a promising adjunctive agent for depression and other mood disorders (Fernandes et al., 2016).

    Daily doses in studies range from 1000–3000 mg, with treatment durations of 8–24 weeks (Peng et al., 2024). The effect is small (SMD = -0.24) and most pronounced in patients with bipolar disorder; it is used as an adjunctive agent, not as a standalone treatment.

    There is evidence supporting its recommendation for significantly reducing negative symptoms and overall symptom severity in schizophrenia (Yolland et al., 2020).

  • 3) Omega-3 (EPA-predominant)

    The formulations found effective in depression are EPA-predominant. The ISNPR guideline recommends pure EPA or formulations with an EPA/DHA ratio greater than 2, at a daily dose providing 1–2 g of EPA (Guu et al., 2019). Meta-analyses also show that the effect becomes more pronounced as the proportion of EPA increases (Liao et al., 2019). No antidepressant effect has been demonstrated for DHA-predominant formulations.

    Limitations of the evidence: A Cochrane review found that omega-3 has a small effect on depression, with low-certainty evidence; it should be considered an adjunct, not a standalone treatment (Appleton et al., 2021).

  • 4) Citicoline

    Its effects in psychiatry are adjunctive, and the evidence remains limited. It has mainly been studied in depression, negative symptoms of schizophrenia, and addiction.

    Evidence for its psychiatric use is limited to two small randomized trials; there is no meta-analytic evidence (Roohi-Azizi et al., 2017; Brown and Gabrielson, 2012).

  • 5) L-methylfolate (high dose)

    L-methylfolate (15 mg/day) added to an antidepressant has been shown to increase response rates in major depression unresponsive to SSRIs (Papakostas et al., 2012); a meta-analysis found a small to moderate effect (Maruf et al., 2022).

  • 6) Vitamin D and B vitamins (especially folate and B12)

    We do not specify a target blood level: The Endocrine Society's 2024 guideline does not recommend routine vitamin D testing or setting targets based on blood levels in the general adult population (Demay et al., 2024). If a deficiency is identified, replacement therapy is prescribed at your physician's discretion.

    A dose-response meta-analysis found that vitamin D supplementation has a small effect on depression scores, with limited certainty of evidence (Ghaemi et al., 2024). There is no evidence that folate or B12 alone treats depression; benefits are seen primarily in people with deficiencies and when used as adjunctive treatment (Almeida et al., 2015; Young et al., 2019).

  • 7) Probiotics

    There is growing, but still mixed, evidence that adjunctive probiotics may produce small to moderate reductions in depressive symptoms and improve cognitive function in major depression (Asad et al., 2025; Liu et al., 2019) — 23 randomized trials, 1401 patients; the effect is small, and consistency across studies is low.

  • 8) Magnesium

    Observational studies show an association between magnesium status and sleep quality, but randomized trials have yielded conflicting results, and the certainty of evidence is low (Arab et al., 2023; Mah and Pitre, 2021).

    • In older patients with insomnia, 500 mg/day of magnesium oxide for 8 weeks was reported to significantly improve sleep duration, sleep efficiency, sleep onset latency, and melatonin levels (Abbasi et al., 2012).
    • In healthy young to middle-aged adults reporting poor sleep, 250 mg/day of magnesium bisglycinate reduced insomnia scores compared with placebo, with a significant but small effect (Schuster et al., 2025).
    • The L-threonate form, taken at 1 g/day for 21 days, was reported to improve deep and REM sleep, daytime energy, and productivity (Hausenblas et al., 2024).
    FormSettings in which it stands out
    Magnesium oxidePrimary insomnia in older adults, postoperative patients
    Magnesium citrateInsomnia in older adults
    Magnesium bisglycinateHealthy adults with poor sleep quality
    Magnesium L-threonatePeople with poor sleep accompanied by cognitive or mood complaints

    Study doses are generally 250–500 mg/day of elemental magnesium, taken in the evening or before bedtime for 4–8 weeks. Better-absorbed forms: bisglycinate, citrate, L-threonate. A budget-friendly form supported by evidence: oxide. People with renal failure or serious cardiac arrhythmias should use it only under medical supervision.

Reminder: use these supplements only if your doctor recommends them, and never change your current treatment on your own.

Kaynaklar

  1. Mahmoudi R, Mohammadi-Sartang M, Servatyari K, ve ark. Effect of saffron on depression, anxiety and mood disorder: a GRADE assessed systematic review and meta-analysis of 34 randomized controlled trials. Nutritional Neuroscience. 2026;29(7):816-837. https://doi.org/10.1080/1028415X.2025.2602153 · PMID: 41693488
  2. Shafiee A, Jafarabady K, Seighali N, ve ark. Effect of Saffron Versus Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment of Depression and Anxiety: A Meta-analysis of Randomized Controlled Trials. Nutrition Reviews. 2025;83(3):e751-e761. https://doi.org/10.1093/nutrit/nuae076 · PMID: 38913392
  3. Marx W, Lane M, Rocks T, ve ark. Effect of saffron supplementation on symptoms of depression and anxiety: a systematic review and meta-analysis. Nutrition Reviews. 2019;77(8):557-571. https://doi.org/10.1093/nutrit/nuz023 · PMID: 31135916
  4. Lian J, Zhong Y, Li H, ve ark. Effects of saffron supplementation on improving sleep quality: a meta-analysis of randomized controlled trials. Sleep Medicine. 2022;92:24-33. https://doi.org/10.1016/j.sleep.2022.03.001 · PMID: 35325766
  5. Peng TR, Lin HH, Tseng TL, ve ark. Efficacy of N-acetylcysteine for patients with depression: An updated systematic review and meta-analysis. General Hospital Psychiatry. 2024;91:151-159. https://doi.org/10.1016/j.genhosppsych.2024.10.018 · PMID: 39504621
  6. Fernandes BS, Dean OM, Dodd S, ve ark. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. Journal of Clinical Psychiatry. 2016;77(4):e457-e466. https://doi.org/10.4088/JCP.15r09984 · PMID: 27137430
  7. Yolland CO, Hanratty D, Neill E, ve ark. Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia. Australian & New Zealand Journal of Psychiatry. 2020;54(5):453-466. https://doi.org/10.1177/0004867419893439 · PMID: 31826654
  8. Guu TW, Mischoulon D, Sarris J, ve ark. International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder. Psychotherapy and Psychosomatics. 2019;88(5):263-273. https://doi.org/10.1159/000502652 · PMID: 31480057
  9. Liao Y, Xie B, Zhang H, ve ark. Efficacy of omega-3 PUFAs in depression: A meta-analysis. Translational Psychiatry. 2019;9(1):190. https://doi.org/10.1038/s41398-019-0515-5 · PMID: 31383846
  10. Appleton KM, Voyias PD, Sallis HM, ve ark. Omega-3 fatty acids for depression in adults. Cochrane Database of Systematic Reviews. 2021;11(11):CD004692. https://doi.org/10.1002/14651858.CD004692.pub5 · PMID: 34817851
  11. Roohi-Azizi M, Arabzadeh S, Amidfar M, ve ark. Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. Clinical Neuropharmacology. 2017;40(1):1-5. https://doi.org/10.1097/WNF.0000000000000185 · PMID: 28085707
  12. Brown ES, Gabrielson B. A randomized, double-blind, placebo-controlled trial of citicoline for bipolar and unipolar depression and methamphetamine dependence. Journal of Affective Disorders. 2012;143(1-3):257-260. https://doi.org/10.1016/j.jad.2012.05.006 · PMID: 22974472
  13. Maruf AA, Poweleit EA, Brown LC, ve ark. Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders. Pharmacopsychiatry. 2022;55(3):139-147. https://doi.org/10.1055/a-1681-2047 · PMID: 34794190
  14. Papakostas GI, Shelton RC, Zajecka JM, ve ark. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. American Journal of Psychiatry. 2012;169(12):1267-1274. https://doi.org/10.1176/appi.ajp.2012.11071114 · PMID: 23212058
  15. Ghaemi S, Zeraattalab-Motlagh S, Jayedi A, ve ark. The effect of vitamin D supplementation on depression: a systematic review and dose-response meta-analysis of randomized controlled trials. Psychological Medicine. 2024;54(15):3999-4008. https://doi.org/10.1017/S0033291724001697 · PMID: 39552387
  16. Demay MB, Pittas AG, Bikle DD, ve ark. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism. 2024;109(8):1907-1947. https://doi.org/10.1210/clinem/dgae290 · PMID: 38828931
  17. Holick MF, Binkley NC, Bischoff-Ferrari HA, ve ark. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2011;96(7):1911-1930. https://doi.org/10.1210/jc.2011-0385 · PMID: 21646368
  18. Almeida OP, Ford AH, Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. International Psychogeriatrics. 2015;27(5):727-737. https://doi.org/10.1017/S1041610215000046 · PMID: 25644193
  19. Young LM, Pipingas A, White DJ, ve ark. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals. Nutrients. 2019;11(9):2232. https://doi.org/10.3390/nu11092232 · PMID: 31527485
  20. Asad A, Kirk M, Zhu S, ve ark. Effects of Prebiotics and Probiotics on Symptoms of Depression and Anxiety in Clinically Diagnosed Samples: Systematic Review and Meta-analysis of Randomized Controlled Trials. Nutrition Reviews. 2025;83(7):e1504-e1520. https://doi.org/10.1093/nutrit/nuae177 · PMID: 39731509
  21. Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neuroscience & Biobehavioral Reviews. 2019;102:13-23. https://doi.org/10.1016/j.neubiorev.2019.03.023 · PMID: 31004628
  22. Arab A, Rafie N, Amani R, ve ark. The Role of Magnesium in Sleep Health: a Systematic Review of Available Literature. Biological Trace Element Research. 2023;201(1):121-128. https://doi.org/10.1007/s12011-022-03162-1 · PMID: 35184264
  23. Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC Complementary Medicine and Therapies. 2021;21(1):125. https://doi.org/10.1186/s12906-021-03297-z · PMID: 33865376
  24. Abbasi B, Kimiagar M, Sadeghniiat K, ve ark. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences. 2012;17(12):1161-1169. PMID: 23853635
  25. Schuster J, Cycelskij I, Lopresti A, ve ark. Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial. Nature and Science of Sleep. 2025;17:2027-2040. https://doi.org/10.2147/NSS.S524348 · PMID: 40918053
  26. Hausenblas HA, Lynch T, Hooper S, ve ark. Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial. Sleep Medicine: X. 2024;8:100121. https://doi.org/10.1016/j.sleepx.2024.100121 · PMID: 39252819

The literature search for this text was conducted using the PubMed database.

Sitenin son güncellemesi: 8 Kasım 2026 · Site editörü: Doç. Dr. Alişan Burak Yaşar, info@alisanburak.com