Published Support for Hedonia

Here we present key publications that support the use of Hedonia nutrients in depression.

These studies are mostly clinical studies testing nutritional intervention at relevant doses and duration. Additional epidemiological studies and meta-analyses are included as appropriate.

HedoniaUSA has produced a medical dossier describing in detail the literature supporting Hedonia as a medical food for the nutritional management of depression. For a copy of this, please write to

Hedonia box, blister pack, and capsules

Folate Publications

Morris et al in 2003 studied approximately 3000 volunteers in the US, showing that those with depression had a lower blood folate level than those without depression. This important work establishes the claim that depression is related to a deficiency in folate levels.

Furthermore, there is an association of certain genetic variations in the MTHFR gene which supports use of L-methylfolate as an intervention. This is supported by the studies by Kelly, Lewis, Stengler and Wan.

The meta-analysis and review by Sarris shows that across the studies performed with L-methylfolate there is a significant effect on depression.

Abou-Saleh, M. T., and A. Coppen. “Serum and Red Blood Cell Folate in Depression.” Acta Psychiatr Scand 80, no. 1 (Jul 1989): 78-82.

Alpert, J. E., D. Mischoulon, G. E. Rubenstein, K. Bottonari, A. A. Nierenberg, and M. Fava. “Folinic Acid (Leucovorin) as an Adjunctive Treatment for Ssri-Refractory Depression.” Ann Clin Psychiatry 14, no. 1 (Mar 2002): 33-8.

Colson, N. J., H. L. Naug, E. Nikbakht, P. Zhang, and J. McCormack. “The Impact of Mthfr 677 C/T Genotypes on Folate Status Markers: A Meta-Analysis of Folic Acid Intervention Studies.” Eur J Nutr 56, no. 1 (Feb 2017): 247-60.

Dartois, L. L., D. L. Stutzman, and M. Morrow. “L-Methylfolate Augmentation to Antidepressants for Adolescents with Treatment-Resistant Depression: A Case Series.” J Child Adolesc Psychopharmacol 29, no. 5 (Jun 2019): 386-91.

Freeman, M. P., G. M. Savella, T. R. Church, L. Góez-Mogollón, A. Z. Sosinsky, O. B. Noe, A. Kaimal, and L. S. Cohen. “A Prenatal Supplement with Methylfolate for the Treatment and Prevention of Depression in Women Trying to Conceive and During Pregnancy.” Ann Clin Psychiatry 31, no. 1 (Feb 2019): 4-16.

Ginsberg, L. D., A. Y. Oubre, and Y. A. Daoud. “L-Methylfolate Plus Ssri or Snri from Treatment Initiation Compared to Ssri or Snri Monotherapy in a Major Depressive Episode.” Innov Clin Neurosci 8, no. 1 (Jan 2011): 19-28.

Godfrey, P. S., B. K. Toone, M. W. Carney, T. G. Flynn, T. Bottiglieri, M. Laundy, I. Chanarin, and E. H. Reynolds. “Enhancement of Recovery from Psychiatric Illness by Methylfolate.” Lancet 336, no. 8712 (Aug 18 1990): 392-5.

Kelly, C. B., A. P. McDonnell, T. G. Johnston, C. Mulholland, S. J. Cooper, D. McMaster, A. Evans, and A. S. Whitehead. “The Mthfr C677t Polymorphism Is Associated with Depressive Episodes in Patients from Northern Ireland.” J Psychopharmacol 18, no. 4 (Dec 2004): 567-71.

Lewis, S. J., R. Araya, S. Leary, G. D. Smith, and A. Ness. “Folic Acid Supplementation During Pregnancy May Protect against Depression 21 Months after Pregnancy, an Effect Modified by Mthfr C677t Genotype.” Eur J Clin Nutr 66, no. 1 (Jan 2012): 97-103.

Lewis, S. J., D. A. Lawlor, G. Davey Smith, R. Araya, N. Timpson, I. N. Day, and S. Ebrahim. “The Thermolabile Variant of Mthfr Is Associated with Depression in the British Women’s Heart and Health Study and a Meta-Analysis.” Mol Psychiatry 11, no. 4 (Apr 2006): 352-60.

Morris, M. S., M. Fava, P. F. Jacques, J. Selhub, and I. H. Rosenberg. “Depression and Folate Status in the US Population.” Psychother Psychosom 72, no. 2 (Mar-Apr 2003): 80-7.

Murakami, K., T. Mizoue, S. Sasaki, M. Ohta, M. Sato, Y. Matsushita, and N. Mishima. “Dietary Intake of Folate, Other B Vitamins, and Omega-3 Polyunsaturated Fatty Acids in Relation to Depressive Symptoms in Japanese Adults.” Nutrition 24, no. 2 (Feb 2008): 140-7.

Nierenberg, A. A., R. Montana, G. Kinrys, T. Deckersbach, S. Dufour, and J. H. Baek. “L-Methylfolate for Bipolar I Depressive Episodes: An Open Trial Proof-of-Concept Registry.” J Affect Disord 207 (Jan 1 2017): 429-33.

Papakostas, G. I., R. C. Shelton, J. M. Zajecka, T. Bottiglieri, J. Roffman, C. Cassiello, S. M. Stahl, and M. Fava. “Effect of Adjunctive L-Methylfolate 15 Mg among Inadequate Responders to Ssris in Depressed Patients Who Were Stratified by Biomarker Levels and Genotype: Results from a Randomized Clinical Trial.” J Clin Psychiatry 75, no. 8 (Aug 2014): 855-63.

Papakostas, G. I., R. C. Shelton, J. M. Zajecka, B. Etemad, K. Rickels, A. Clain, L. Baer, E. D. Dalton, G. R. Sacco, D. Schoenfeld, M. Pencina, A. Meisner, T. Bottiglieri, E. Nelson, D. Mischoulon, J. E. Alpert, J. G. Barbee, S. Zisook, and M. Fava. “L-Methylfolate as Adjunctive Therapy for Ssri-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials.” Am J Psychiatry 169, no. 12 (Dec 2012): 1267-74.

Ramos, M. I., L. H. Allen, M. N. Haan, R. Green, and J. W. Miller. “Plasma Folate Concentrations Are Associated with Depressive Symptoms in Elderly Latina Women Despite Folic Acid Fortification.” Am J Clin Nutr 80, no. 4 (Oct 2004): 1024-8.

Roberts, E., B. Carter, and A. H. Young. “Caveat Emptor: Folate in Unipolar Depressive Illness, a Systematic Review and Meta-Analysis.” J Psychopharmacol 32, no. 4 (Apr 2018): 377-84.

Sarris, J., J. Murphy, D. Mischoulon, G. I. Papakostas, M. Fava, M. Berk, and C. H. Ng. “Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses.” Am J Psychiatry 173, no. 6 (Jun 1 2016): 575-87.

Shelton, R. C., M. J. Pencina, L. W. Barrentine, J. A. Ruiz, M. Fava, J. M. Zajecka, and G. I. Papakostas. “Association of Obesity and Inflammatory Marker Levels on Treatment Outcome: Results from a Double-Blind, Randomized Study of Adjunctive L-Methylfolate Calcium in Patients with Mdd Who Are Inadequate Responders to Ssris.” J Clin Psychiatry 76, no. 12 (Dec 2015): 1635-41.

Shelton, R. C., J. Sloan Manning, L. W. Barrentine, and E. V. Tipa. “Assessing Effects of L-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial.” Prim Care Companion CNS Disord 15, no. 4 (2013).

Stengler, M. “The Role of Folate and Mthfr Polymorphisms in the Treatment of Depression.” Altern Ther Health Med 27, no. 2 (Mar 2021): 53-57.

Tolmunen, T., J. Hintikka, A. Ruusunen, S. Voutilainen, A. Tanskanen, V. P. Valkonen, H. Viinamäki, G. A. Kaplan, and J. T. Salonen. “Dietary Folate and the Risk of Depression in Finnish Middle-Aged Men. A Prospective Follow-up Study.” Psychother Psychosom 73, no. 6 (Nov-Dec 2004): 334-9.

Tolmunen, T., S. Voutilainen, J. Hintikka, T. Rissanen, A. Tanskanen, H. Viinamäki, G. A. Kaplan, and J. T. Salonen. “Dietary Folate and Depressive Symptoms Are Associated in Middle-Aged Finnish Men.” J Nutr 133, no. 10 (Oct 2003): 3233-6.

Wade, R. L., S. L. Kindermann, Q. Hou, and M. E. Thase. “Comparative Assessment of Adherence Measures and Resource Use in Ssri/Snri-Treated Patients with Depression Using Second-Generation Antipsychotics or L-Methylfolate as Adjunctive Therapy.” J Manag Care Pharm 20, no. 1 (Jan 2014): 76-85.

Wan, L., Y. Li, Z. Zhang, Z. Sun, Y. He, and R. Li. “Methylenetetrahydrofolate Reductase and Psychiatric Diseases.” Transl Psychiatry 8, no. 1 (Nov 5 2018): 242.

Zajecka, J. M., M. Fava, R. C. Shelton, L. W. Barrentine, P. Young, and G. I. Papakostas. “Long-Term Efficacy, Safety, and Tolerability of L-Methylfolate Calcium 15 Mg as Adjunctive Therapy with Selective Serotonin Reuptake Inhibitors: A 12-Month, Open-Label Study Following a Placebo-Controlled Acute Study.” J Clin Psychiatry 77, no. 5 (May 2016): 654-60.

Omega-3 Publications

Carney et al show that the baseline O3 index is related to outcome – this supports the nutritionally defined O3 index is related to depression.


Amini, M., F. Bahmani, F. Foroozanfard, Z. Vahedpoor, A. Ghaderi, M. Taghizadeh, H. Karbassizadeh, and Z. Asemi. “The Effects of Fish Oil Omega-3 Fatty Acid Supplementation on Mental Health Parameters and Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.” J Psychosom Obstet Gynaecol  (Sep 19 2018): 1-9.

Carney, R. M., B. C. Steinmeyer, K. E. Freedland, E. H. Rubin, M. W. Rich, and W. S. Harris. “Baseline Blood Levels of Omega-3 and Depression Remission: A Secondary Analysis of Data from a Placebo-Controlled Trial of Omega-3 Supplements.” J Clin Psychiatry 77, no. 2 (Feb 2016): e138-43.

Chang, J. P., S. S. Chang, H. T. Yang, H. T. Chen, Y. C. Chien, B. Yang, H. Su, and K. P. Su. “Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Diseases Comorbid Major Depressive Disorder – Results from a Randomized Controlled Trial.” Brain Behav Immun 85 (Mar 2020): 14-20.

Dashti-Khavidaki, S., A. Gharekhani, M. R. Khatami, E. S. Miri, H. Khalili, E. Razeghi, S. S. Hashemi-Nazari, and M. A. Mansournia. “Effects of Omega-3 Fatty Acids on Depression and Quality of Life in Maintenance Hemodialysis Patients.” Am J Ther 21, no. 4 (Jul-Aug 2014): 275-87.

Fristad, M. A., A. T. Vesco, A. S. Young, K. Z. Healy, E. S. Nader, W. Gardner, A. M. Seidenfeld, H. L. Wolfson, and L. E. Arnold. “Pilot Randomized Controlled Trial of Omega-3 and Individual-Family Psychoeducational Psychotherapy for Children and Adolescents with Depression.” J Clin Child Adolesc Psychol 48, no. sup1 (2019): S105-s18.

Ganança, L., H. C. Galfalvy, M. A. Oquendo, A. Hezghia, T. B. Cooper, J. J. Mann, and M. E. Sublette. “Lipid Correlates of Antidepressant Response to Omega-3 Polyunsaturated Fatty Acid Supplementation: A Pilot Study.” Prostaglandins Leukot Essent Fatty Acids 119 (Apr 2017): 38-44.

Haberka, M., K. Mizia-Stec, M. Mizia, K. Gieszczyk, A. Chmiel, K. Sitnik-Warchulska, and Z. Gąsior. “Effects of N-3 Polyunsaturated Fatty Acids on Depressive Symptoms, Anxiety and Emotional State in Patients with Acute Myocardial Infarction.” Pharmacol Rep 65, no. 1 (2013): 59-68.

Hashimoto, M., S. Kato, Y. Tanabe, M. Katakura, A. A. Mamun, M. Ohno, S. Hossain, K. Onoda, S. Yamaguchi, and O. Shido. “Beneficial Effects of Dietary Docosahexaenoic Acid Intervention on Cognitive Function and Mental Health of the Oldest Elderly in Japanese Care Facilities and Nursing Homes.” Geriatr Gerontol Int 17, no. 2 (Feb 2017): 330-37.

Jahangard, L., A. Sadeghi, M. Ahmadpanah, E. Holsboer-Trachsler, D. Sadeghi Bahmani, M. Haghighi, and S. Brand. “Influence of Adjuvant Omega-3-Polyunsaturated Fatty Acids on Depression, Sleep, and Emotion Regulation among Outpatients with Major Depressive Disorders – Results from a Double-Blind, Randomized and Placebo-Controlled Clinical Trial.” J Psychiatr Res 107 (Dec 2018): 48-56.

Jamilian, M., M. Samimi, N. Mirhosseini, F. Afshar Ebrahimi, E. Aghadavod, R. Talaee, S. Jafarnejad, S. Hashemi Dizaji, and Z. Asemi. “The Influences of Vitamin D and Omega-3 Co-Supplementation on Clinical, Metabolic and Genetic Parameters in Women with Polycystic Ovary Syndrome.” J Affect Disord 238 (Oct 1 2018): 32-38.

Jamilian, M., A. Shojaei, M. Samimi, F. Afshar Ebrahimi, E. Aghadavod, M. Karamali, M. Taghizadeh, H. Jamilian, S. Alaeinasab, S. Jafarnejad, and Z. Asemi. “The Effects of Omega-3 and Vitamin E Co-Supplementation on Parameters of Mental Health and Gene Expression Related to Insulin and Inflammation in Subjects with Polycystic Ovary Syndrome.” J Affect Disord 229 (Mar 15 2018): 41-47.

Jiang, W., D. J. Whellan, K. F. Adams, M. A. Babyak, S. H. Boyle, J. L. Wilson, C. B. Patel, J. G. Rogers, W. S. Harris, and C. M. O’Connor. “Long-Chain Omega-3 Fatty Acid Supplements in Depressed Heart failure patients: Results of the Ocean Trial.” JACC Heart Fail 6, no. 10 (Oct 2018): 833-43.

Kaviani, M., L. Saniee, S. Azima, F. Sharif, and M. Sayadi. “The Effect of Omega-3 Fatty Acid Supplementation on Maternal Depression During Pregnancy: A Double Blind Randomized Controlled Clinical Trial.” Int J Community Based Nurs Midwifery 2, no. 3 (Jul 2014): 142-7.

Keenan, K., A. E. Hipwell, J. Bortner, A. Hoffmann, and R. McAloon. “Association between Fatty Acid Supplementation and Prenatal Stress in African Americans: A Randomized Controlled Trial.” Obstet Gynecol 124, no. 6 (Dec 2014): 1080-87.

Keshavarz, S. A., S. A. Mostafavi, S. Akhondzadeh, M. R. Mohammadi, S. Hosseini, M. R. Eshraghian, and M. Chamari. “Omega-3 Supplementation Effects on Body Weight and Depression among Dieter Women with Co-Morbidity of Depression and Obesity Compared with the Placebo: A Randomized Clinical Trial.” Clin Nutr ESPEN 25 (Jun 2018): 37-43.

Khajehnasiri, F., S. Akhondzadeh, S. B. Mortazavi, A. Allameh, G. Sotoudeh, A. Khavanin, and Z. Zamanian. “Are Supplementation of Omega-3 and Ascorbic Acid Effective in Reducing Oxidative Stress and Depression among Depressed Shift Workers?”, Int J Vitam Nutr Res 85, no. 5-6 (Dec 2015): 299-310.

Masoumi, S. Z., F. Kazemi, S. Tavakolian, A. Rahimi, K. Oshvandi, A. Soltanian, and F. Shobeiri. “Effect of Citalopram in Combination with Omega-3 on Depression in Post-Menopausal Women: A Triple Blind Randomized Controlled Trial.” J Clin Diagn Res 10, no. 10 (Oct 2016): Qc01-qc05.

Mazereeuw, G., N. Herrmann, A. C. Andreazza, G. Scola, D. W. L. Ma, P. I. Oh, and K. L. Lanctôt. “Oxidative Stress Predicts Depressive Symptom Changes with Omega-3 Fatty Acid Treatment in Coronary Artery Disease Patients.” Brain Behav Immun 60 (Feb 2017): 136-41.

McNamara, R. K., J. Strimpfel, R. Jandacek, T. Rider, P. Tso, J. A. Welge, J. R. Strawn, and M. P. Delbello. “Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with Ssri-Resistant Major Depressive Disorder.” PharmaNutrition 2, no. 2 (Apr 1 2014): 38-46.

Nishi, D., K. P. Su, K. Usuda, J. P. Chang, K. Hamazaki, T. Ishima, Y. Sano, H. Ito, K. Isaka, Y. Tachibana, S. Tanigaki, T. Suzuki, K. Hashimoto, and Y. J. Matsuoka. “Plasma Estradiol Levels and Antidepressant Effects of Omega-3 Fatty Acids in Pregnant Women.” Brain Behav Immun 85 (Mar 2020): 29-34.

Parletta, N., D. Zarnowiecki, J. Cho, A. Wilson, S. Bogomolova, A. Villani, C. Itsiopoulos, T. Niyonsenga, S. Blunden, B. Meyer, L. Segal, B. T. Baune, and K. O’Dea. “A Mediterranean-Style Dietary Intervention Supplemented with Fish Oil Improves Diet Quality and Mental Health in People with Depression: A Randomized Controlled Trial (Helfimed).” Nutr Neurosci 22, no. 7 (Jul 2019): 474-87.

Rapaport, M. H., A. A. Nierenberg, P. J. Schettler, B. Kinkead, A. Cardoos, R. Walker, and D. Mischoulon. “Inflammation as a Predictive Biomarker for Response to Omega-3 Fatty Acids in Major Depressive Disorder: A Proof-of-Concept Study.” Mol Psychiatry 21, no. 1 (Jan 2016): 71-9.

Ravi, S., H. Khalili, L. Abbasian, M. Arbabi, and P. Ghaeli. “Effect of Omega-3 Fatty Acids on Depressive Symptoms in Hiv-Positive Individuals: A Randomized, Placebo-Controlled Clinical Trial.” Ann Pharmacother 50, no. 10 (Oct 2016): 797-807.

Smith, D. J., J. Sarris, N. Dowling, M. O’Connor, and C. H. Ng. “Adjunctive Low-Dose Docosahexaenoic Acid (Dha) for Major Depression: An Open-Label Pilot Trial.” Nutr Neurosci 21, no. 3 (Apr 2018): 224-28.

Su, K. P., H. C. Lai, H. T. Yang, W. P. Su, C. Y. Peng, J. P. Chang, H. C. Chang, and C. M. Pariante. “Omega-3 Fatty Acids in the Prevention of Interferon-Alpha-Induced Depression: Results from a Randomized, Controlled Trial.” Biol Psychiatry 76, no. 7 (Oct 1 2014): 559-66.

Trebatická, J., Z. Hradečná, F. Böhmer, M. Vaváková, I. Waczulíková, I. Garaiova, J. Luha, I. Škodáček, J. Šuba, and Z. Ďuračková. “Emulsified Omega-3 Fatty-Acids Modulate the Symptoms of Depressive Disorder in Children and Adolescents: A Pilot Study.” Child Adolesc Psychiatry Ment Health 11 (2017): 30.

Tu, C. H., C. M. Chen, C. C. Yang, P. Gałecki, and K. P. Su. “Brain Responses to Emotional Stimuli after Eicosapentaenoic Acid and Docosahexaenoic Acid Treatments in Major Depressive Disorder: Toward Personalized Medicine with Anti-Inflammatory Nutraceuticals.” J Pers Med 10, no. 4 (Dec 16 2020).

Vesco, A. T., A. S. Young, L. E. Arnold, and M. A. Fristad. “Omega-3 Supplementation Associated with Improved Parent-Rated Executive Function in Youth with Mood Disorders: Secondary Analyses of the Omega 3 and Therapy (Oats) Trials.” J Child Psychol Psychiatry 59, no. 6 (Jun 2018): 628-36.

Young, A. S., L. E. Arnold, H. L. Wolfson, and M. A. Fristad. “Psychoeducational Psychotherapy and Omega-3 Supplementation Improve Co-Occurring Behavioral Problems in Youth with Depression: Results from a Pilot Rct.” J Abnorm Child Psychol 45, no. 5 (Jul 2017): 1025-37.

SAMe Publications

Alpert, J. E., G. Papakostas, D. Mischoulon, J. J. Worthington, 3rd, T. Petersen, Y. Mahal, A. Burns, T. Bottiglieri, A. A. Nierenberg, and M. Fava. “S-Adenosyl-L-Methionine (Same) as an Adjunct for Resistant Major Depressive Disorder: An Open Trial Following Partial or Nonresponse to Selective Serotonin Reuptake Inhibitors or Venlafaxine.” J Clin Psychopharmacol 24, no. 6 (Dec 2004): 661-4.

De Berardis, D., S. Marini, N. Serroni, G. Rapini, F. Iasevoli, A. Valchera, M. Signorelli, E. Aguglia, G. Perna, A. Salone, G. Di Iorio, G. Martinotti, and M. Di Giannantonio. “S-Adenosyl-L-Methionine Augmentation in Patients with Stage Ii Treatment-Resistant Major Depressive Disorder: An Open Label, Fixed Dose, Single-Blind Study.” ScientificWorldJournal 2013 (2013): 204649.

Delle Chiaie, R., P. Pancheri, and P. Scapicchio. “Efficacy and Tolerability of Oral and Intramuscular S-Adenosyl-L-Methionine 1,4-Butanedisulfonate (Same) in the Treatment of Major Depression: Comparison with Imipramine in 2 Multicenter Studies.” Am J Clin Nutr 76, no. 5 (Nov 2002): 1172s-6s.

Di Rocco, A., J. D. Rogers, R. Brown, P. Werner, and T. Bottiglieri. “S-Adenosyl-Methionine Improves Depression in Patients with Parkinson’s Disease in an Open-Label Clinical Trial.” Mov Disord 15, no. 6 (Nov 2000): 1225-9.<1225::aid-mds1025>;2-a.

Kalman, D. S., S. Feldman, R. R. Vazquez, and D. R. Krieger. “A Prospective Randomized Double-Blind Study Evaluating Up165 and S-Adenosyl-L-Methionine on Depression, Anxiety and Psychological Well-Being.” Foods 4, no. 2 (May 8 2015): 130-39.

Levkovitz, Y., J. E. Alpert, C. E. Brintz, D. Mischoulon, and G. I. Papakostas. “Effects of S-Adenosylmethionine Augmentation of Serotonin-Reuptake Inhibitor Antidepressants on Cognitive Symptoms of Major Depressive Disorder.” Eur Psychiatry 27, no. 7 (Oct 2012): 518-21.

Mischoulon, D., L. H. Price, L. L. Carpenter, A. R. Tyrka, G. I. Papakostas, L. Baer, C. M. Dording, A. J. Clain, K. Durham, R. Walker, E. Ludington, and M. Fava. “A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of S-Adenosyl-L-Methionine (Same) Versus Escitalopram in Major Depressive Disorder.” J Clin Psychiatry 75, no. 4 (Apr 2014): 370-6.

Pancheri, P., P. Scapicchio, and R. D. Chiaie. “A Double-Blind, Randomized Parallel-Group, Efficacy and Safety Study of Intramuscular S-Adenosyl-L-Methionine 1,4-Butanedisulphonate (Same) Versus Imipramine in Patients with Major Depressive Disorder.” Int J Neuropsychopharmacol 5, no. 4 (Dec 2002): 287-94.

Papakostas, G. I., D. Mischoulon, I. Shyu, J. E. Alpert, and M. Fava. “S-Adenosyl Methionine (Same) Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders with Major Depressive Disorder: A Double-Blind, Randomized Clinical Trial.” Am J Psychiatry 167, no. 8 (Aug 2010): 942-8.

Rosenbaum, J. F., M. Fava, W. E. Falk, M. H. Pollack, L. S. Cohen, B. M. Cohen, and G. S. Zubenko. “The Antidepressant Potential of Oral S-Adenosyl-L-Methionine.” Acta Psychiatr Scand 81, no. 5 (May 1990): 432-6.

Saccarello, A., P. Montarsolo, I. Massardo, R. Picciotto, A. Pedemonte, R. Castagnaro, P. C. Brasesco, V. Guida, P. Picco, P. Fioravanti, R. Montisci, I. Schiavetti, and A. Vanelli. “Oral Administration of S-Adenosylmethionine (Same) and Lactobacillus Plantarum Heal9 Improves the Mild-to-Moderate Symptoms of Depression: A Randomized, Double-Blind, Placebo-Controlled Study.” Prim Care Companion CNS Disord 22, no. 4 (Jun 25 2020).

Sakurai, H., L. Carpenter L, R. Tyrka A, L. H. Price, I. Papakostas G, C. M. Dording, A. S. Yeung, C. Cusin, E. Ludington, R. Bernard-Negron, M. Fava, and D. Mischoulon. “Dose Increase of S-Adenosyl-Methionine and Escitalopram in a Randomized Clinical Trial for Major Depressive Disorder.” J Affect Disord 262 (Feb 1 2020): 118-25.

Salmaggi, P., G. M. Bressa, G. Nicchia, M. Coniglio, P. La Greca, and C. Le Grazie. “Double-Blind, Placebo-Controlled Study of S-Adenosyl-L-Methionine in Depressed Postmenopausal Women.” Psychother Psychosom 59, no. 1 (1993): 34-40.

Sarris, J., J. Murphy, C. Stough, D. Mischoulon, C. Bousman, P. MacDonald, L. Adams, S. Nazareth, G. Oliver, L. Cribb, K. Savage, R. Menon, S. Chamoli, M. Berk, C. H. Ng, and G. J. Byrne. “S-Adenosylmethionine (Same) Monotherapy for Depression: An 8-Week Double-Blind, Randomised, Controlled Trial.” Psychopharmacology (Berl) 237, no. 1 (Jan 2020): 209-18.

Sarris, J., G. I. Papakostas, O. Vitolo, M. Fava, and D. Mischoulon. “S-Adenosyl Methionine (Same) Versus Escitalopram and Placebo in Major Depression Rct: Efficacy and Effects of Histamine and Carnitine as Moderators of Response.” J Affect Disord 164 (Aug 2014): 76-81.

Sarris, J., L. H. Price, L. L. Carpenter, A. R. Tyrka, C. H. Ng, G. I. Papakostas, A. Jaeger, M. Fava, and D. Mischoulon. “Is S-Adenosyl Methionine (Same) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial.” Pharmacopsychiatry 48, no. 4-5 (Jul 2015): 141-4.

Hedonia® is classified (and regulated) in the USA as a medical food product.

Hedonia is intended to be used under medical supervision alongside an individual’s physician-directed treatment.

Each gel-capsule contains a total omega-3 triglyceride content of 640mg of which EPA is 400mg, 400mg of Adonat® Premium SAMe Stabilized PowdeR, and 3.75mg of Quatrefolic® ((6S)-5-methyltetrahydrofolic acid).


Mono and diglycerides of fatty acids, Lemon natural flavor, sunflower lecithin, gelatin, Firming agent: glycerol, colorant: Titanium dioxide, Coloring: allura red, yellow-orange, and brilliant blue FCF