The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials

World Psychiatry

Volumn 18, Issue 3, 2019, Pages 308-324

  Firth, Joseph ^a,b,c   Teasdale, Scott B ^d,e   Allott, Kelly ^c,f   Siskind, Dan ^g,h   Marx, Wolfgang ⁱ   Cotter, Jack ^j   Veronese, Nicola ^k,l   Schuch, Felipe ^m   Smith, Lee ⁿ   Solmi, Marco ^o,p   Carvalho, André F ^q,r   Vancampfort, Davy ^s,t   Berk, Michael ^f,i   Stubbs, Brendon ^u,v   Sarris, Jerome ^a,w  

^a WESTERN SYDNEY UNIVERSITY   (Australia)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d UNIVERSITY OF NEW SOUTH WALES   (Australia)

^e SOUTH EASTERN SYDNEY LOCAL HEALTH DISTRICT   (Australia)

^f THE NATIONAL CENTRE OF EXCELLENCE IN YOUTH MENTAL HEALTH   (Australia)

^g Metro South Addiction and Mental Health Service   (Australia)

^h UNIVERSITY OF QUEENSLAND   (Australia)

ⁱ DEAKIN UNIVERSITY   (Australia)

^j CAMBRIDGE COGNITION   (United Kingdom)

^k CNR   (Italy)

^l NATIONAL INSTITUTE FOR DIGESTIVE DISEASES   (Italy)

^m FEDERAL UNIVERSITY OF SANTA MARIA   (Brazil)

ⁿ ANGLIA RUSKIN UNIVERSITY   (United Kingdom)

^o UNIVERSITY OF PADOVA   (Italy)

^p UNIVERSITY OF PADUA MEDICAL SCHOOL   (Italy)

^q CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^r UNIVERSITY OF TORONTO   (Canada)

^s KU LEUVEN DEPARTMENT OF REHABILITATION SCIENCES   (Belgium)

^t UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^u SOUTH LONDON AND MAUDSLEY NHS FOUNDATION TRUST   (United Kingdom)

^v KING'S COLLEGE LONDON   (United Kingdom)

^w UNIVERSITY OF MELBOURNE   (Australia)

more..

Author keywords

adjunctive treatment; attention deficit hyperactivity disorder; depression; eicosapentaenoic acid; methylfolate; N acetylcysteine; Nutrient supplements; omega 3; polyunsaturated fatty acids; schizophrenia; vitamin D

Indexed keywords

ACETYLCYSTEINE; AMINO ACID; ANTIOXIDANT; DOCOSAHEXAENOIC ACID; FOLIC ACID; FOLINIC ACID; ICOSAPENTAENOIC ACID; INOSITOL; LINOLEIC ACID; MINERAL; NUTRITION SUPPLEMENT; OMEGA 3 FATTY ACID; POLYUNSATURATED FATTY ACID; PREBIOTIC AGENT; PROBIOTIC AGENT; PSYCHOTROPIC AGENT; SARCOSINE; VITAMIN; VITAMIN D;

ANTIOXIDANT ACTIVITY; ANXIETY DISORDER; ARTICLE; ATTENTION DEFICIT DISORDER; BIPOLAR DISORDER; CALORIC INTAKE; COGNITIVE DEFECT; DEPRESSION; DIET SUPPLEMENTATION; DIETARY INTAKE; DRUG EFFICACY; DRUG SAFETY; HAMILTON ANXIETY SCALE; HUMAN; MAJOR DEPRESSION; MENTAL DISEASE; MENTAL HEALTH; META ANALYSIS; MILD COGNITIVE IMPAIRMENT; MOOD DISORDER; OUTCOME ASSESSMENT; PREMENSTRUAL DYSPHORIC DISORDER; PRIORITY JOURNAL; PSYCHOSIS; QUALITY CONTROL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SCHIZOPHRENIA; SYSTEMATIC REVIEW; TARDIVE DYSKINESIA;

EID: 85068232792     PISSN: 17238617     EISSN: 20515545     Source Type: Journal    
DOI: 10.1002/wps.20672     Document Type: Article

References (110)

1. Firth J, Stubbs B, Teasdale SB et al. Diet as a hot topic in psychiatry: a population-scale study of nutritional intake and inflammatory potential in severe mental illness. World Psychiatry 2018;17:365-7.
2. Teasdale SB, Ward PB, Samaras K et al. Dietary intake of people with severe mental illness: systematic review and meta-analysis. Br J Psychiatry 2019;214:251-9.
3. van den Berk-Clark C, Secrest S, Walls J et al. Association between posttraumatic stress disorder and lack of exercise, poor diet, obesity, and co-occuring smoking: a systematic review and meta-analysis. Health Psychol 2018;37:407-16.
4. Woo H, Kim D, Hong Y-S et al. Dietary patterns in children with attention deficit/hyperactivity disorder (ADHD). Nutrients 2014;6:1539-53.
5. Howard AL, Robinson M, Smith GJ et al. ADHD is associated with a “Western” dietary pattern in adolescents. J Atten Disord 2011;15:403-11.
6. Jacka FN, Cherbuin N, Anstey KJ et al. Does reverse causality explain the relationship between diet and depression? J Affect Disord 2015;175:248-50.
7. Salvi V, Mencacci C, Barone-Adesi F. H1-histamine receptor affinity predicts weight gain with antidepressants. Eur Neuropsychopharmacol 2016;26:1673-7.
8. Firth J, Teasdale SB, Jackson SE et al. Do reductions in ghrelin contribute towards antipsychotic-induced weight gain? Schizophr Res (in press).
9. Tolkien K, Bradburn S, Murgatroyd C. An anti-inflammatory diet as a potential intervention for depressive disorders: a systematic review and meta-analysis. Clin Nutr (in press).
10. Lassale C, Batty GD, Baghdadli A et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry 2019;24:965-86.
11. Firth J, Carney R, Stubbs B et al. Nutritional deficiencies and clinical correlates in first-episode psychosis: a systematic review and meta-analysis. Schizophr Bull 2018;44:1275-92.
12. Swinburn BA, Kraak VI, Allender S et al. The global syndemic of obesity, undernutrition, and climate change: the Lancet Commission report. Lancet 2019;393:791-846.
13. GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2019;393:1958-72.
14. Sarris J, Logan AC, Akbaraly TN et al. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry 2015;2:271-4.
15. Sarris J, Logan AC, Akbaraly TN et al. International Society for Nutritional Psychiatry Research consensus position statement: nutritional medicine in modern psychiatry. World Psychiatry 2015;14:370-1.
16. Fernstrom JD. Can nutrient supplements modify brain function? Am J Clin Nutr 2000;71:1669S-73S.
17. Kantor ED, Rehm CD, Du M et al. Trends in dietary supplement use among US adults from 1999-2012. JAMA 2016;316:1464-74.
18. Wactawski-Wende J, Kotchen JM, Anderson GL et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684-96.
19. Jenkins DJ, Spence JD, Giovannucci EL et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71:2570-84.
20. Lonn E, Bosch J, Yusuf S et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-47.
21. Pitkin RM. Folate and neural tube defects. Am J Clin Nutr 2007;85:285S-8S.
22. Lederle FA. Oral cobalamin for pernicious anemia: medicine's best kept secret? JAMA 1991;265: 94-5.
23. Ala A, Walker AP, Ashkan K et al. Wilson's disease. Lancet 2007;369:397-408.
24. Siscovick DS, Barringer TA, Fretts AM et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American Heart Association. Circulation 2017;135:e867-84.
25. Berk M, Jacka FN. Diet and depression – from confirmation to implementation. JAMA 2019;321:842-3.
26. Berk M, Williams LJ, Jacka FN et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 2013;11:200.
27. Miller BJ, Buckley P, Seabolt W et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011;70:663-71.
28. Berk M, Kapczinski F, Andreazza A et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 2011;35:804-17.
29. Irwin MR, Piber D. Insomnia and inflammation: a two hit model of depression risk and prevention. World Psychiatry 2018;17:359-61.
30. Köhler CA, Freitas TH, Stubbs B et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol 2018;55:4195-4206.
31. Schuch FB, Deslandes AC, Stubbs B et al. Neurobiological effects of exercise on major depressive disorder: a systematic review. Neurosci Biobehav Rev 2016;61:1-11.
32. Dodd S, Dean O, Copolov DL et al. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther 2008;8:1955-62.
33. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002;21:495-505.
34. Swardfager W, Herrmann N, Mazereeuw G et al. Zinc in depression: a meta-analysis. Biol Psychiatry 2013;74:872-8.
35. Joe P, Petrilli M, Malaspina D et al. Zinc in schizophrenia: a meta-analysis. Gen Hosp Psychiatry 2018;53:19-24.
36. Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol Commun Health 2007;61:631-7.
37. Belbasis L, Kohler CA, Stefanis N et al. Risk factors and peripheral biomarkers for schizophrenia spectrum disorders: an umbrella review of meta-analyses. Acta Psychiatr Scand 2018;137:88-97.
38. Anglin RES, Samaan Z, Walter SD et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry 2013;202:100-7.
39. Murri MB, Respino M, Masotti M et al. Vitamin D and psychosis: mini meta-analysis. Schizophr Res 2013;150:235-9.
40. Lally J, Ajnakina O, Singh N et al. Vitamin D and clinical symptoms in first episode psychosis (FEP): a prospective cohort study. Schizophr Res 2019;204:381-8.
41. Zheng P, Zeng B, Liu M et al. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci Adv 2019;5:eaau8317.
42. Valles-Colomer M, Falony G, Darzi Y et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol 2019;4:623-32.
43. Biesalski HK. Nutrition meets the microbiome: micronutrients and the microbiota. Ann NY Acad Sci 2016;1372:53-64.
44. Delzenne NM, Neyrinck AM, Bäckhed F et al. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol 2011;7:639.
45. Dash S, Clarke G, Berk M et al. The gut microbiome and diet in psychiatry: focus on depression. Curr Opin Psychiatry 2015;28:1-6.
46. Kaplan BJ, Rucklidge JJ, Romijn A et al. The emerging field of nutritional mental health: inflammation, the microbiome, oxidative stress, and mitochondrial function. Clin Psychol Sci 2015;3:964-80.
47. Bot M, Brouwer IA, Roca M et al. Effect of multinutrient supplementation and food-related behavioral activation therapy on prevention of major depressive disorder among overweight or obese adults with subsyndromal depressive symptoms: the MooDFOOD randomized clinical trial. JAMA 2019;321:858-68.
48. Freedman R, Hunter SK, Hoffman MC. Prenatal primary prevention of mental illness by micronutrient supplements in pregnancy. Am J Psychiatry 2018;175:607-19.
49. Moher D, Liberati A, Tetzlaff J et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.
50. Shea BJ, Reeves BC, Wells G et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017;358:j4008.
51. Hallahan B, Ryan T, Hibbeln JR et al. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. Br J Psychiatry 2016;209:192-201.
52. Bergman H, Walker DM, Nikolakopoulou A et al. Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia. Health Technol Assess 2017;21:1-218.
53. Firth J, Stubbs B, Sarris J et al. The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis. Psychol Med 2017;47:1515-27.
54. Sakuma K, Matsunaga S, Nomura I et al. Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis. Psychopharmacology 2018:235:2303-14.
55. Fusar-Poli P, Berger G. Eicosapentaenoic acid interventions in schizophrenia: meta-analysis of randomized, placebo-controlled studies. J Clin Psychopharmacol 2012;32:179-85.
56. Zheng W, Zhang QE, Cai DB et al. N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials. Acta Psychiatr Scand 2018;137:391-400.
57. Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 2011;25:859-85.
58. Siskind DJ, Lee M, Ravindran A et al. Augmentation strategies for clozapine refractory schizophrenia: a systematic review and meta-analysis. Aust N Z J Psychiatry 2018;52:751-67.
59. Grosso G, Pajak A, Marventano S et al. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One 2014;9:e96905.
60. Davies C, Cipriani A, Ioannidis JPA et al. Lack of evidence to favor specific preventive interventions in psychosis: a network meta-analysis. World Psychiatry 2018;17:196-209.
61. Devoe DJ, Farris MS, Townes P et al. Attenuated psychotic symptom interventions in youth at risk of psychosis: a systematic review and meta-analysis. Early Interv Psychiatry 2019;13:3-17.
62. Devoe DJ, Peterson A, Addington J. Negative symptom interventions in youth at risk of psychosis: a systematic review and network meta-analysis. Schizophr Bull 2018;44:807-23.
63. Devoe DJ, Farris MS, Townes P et al. Interventions and social functioning in youth at risk of psychosis: a systematic review and meta-analysis. Early Interv Psychiatry 2019;13:169-80.
64. Mocking RJ, Harmsen I, Assies J et al. Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry 2016;6:e756.
65. Schefft C, Kilarski LL, Bschor T et al. Efficacy of adding nutritional supplements in unipolar depression: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2017;27:1090-109.
66. Bae JH, Kim G. Systematic review and meta-analysis of omega-3-fatty acids in elderly patients with depression. Nutr Res 2018;50:1-9.
67. Roberts E, Carter B, Young AH. Caveat emptor: folate in unipolar depressive illness, a systematic review and meta-analysis. J Psychopharmacol 2018;32:377-84.
68. Mukai T, Kishi T, Matsuda Y et al. A meta-analysis of inositol for depression and anxiety disorders. Hum Psychopharmacol 2014;29:55-63.
69. Vellekkatt F, Menon V. Efficacy of vitamin D supplementation in major depression: a meta-analysis of randomized controlled trials. J Postgrad Med 2019;65:74-80.
70. Phelan D, Molero P, Martinez-Gonzalez MA et al. Magnesium and mood disorders: systematic review and meta-analysis. BJPsych Open 2018;4:167-79.
71. Ng QX, Peters C, Ho CYX et al. A meta-analysis of the use of probiotics to alleviate depressive symptoms. J Affect Disord 2018;228:13-9.
72. Fernandes BS, Dean OM, Dodd S et al. N-acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry 2016;77:e457-e66.
73. Sarris J, Murphy J, Mischoulon D et al. Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Am J Psychiatry 2016;173:575-87.
74. Couto JP, Moreira R. Oral N-acetylcysteine in the treatment of obsessive-compulsive disorder: a systematic review of the clinical evidence. Prog Neuropsychopharmacol Biol Psychiatry 2018;86:245-54.
75. Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry 2012;73:81-6.
76. Rosenblat JD, Kakar R, Berk M et al. Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Disord 2016;18:89-101.
77. Puri BK, Martins JG. Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids 2014;90:179-89.
78. Goode AP, Coeytaux RR, Maslow GR et al. Nonpharmacologic treatments for attention-deficit/hyperactivity disorder: a systematic review. Pediatrics 2018;141:e20180094.
79. Hawkey E, Nigg JT. Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev 2014;34:496-505.
80. Cooper RE, Tye C, Kuntsi J et al. The effect of omega-3 polyunsaturated fatty acid supplementation on emotional dysregulation, oppositional behaviour and conduct problems in ADHD: a systematic review and meta-analysis. J Affect Disord 2016;190:474-82.
81. Chang JPC, Su KP, Mondelli V et al. Omega-3 polyunsaturated fatty acids in youths with attention deficit hyperactivity disorder: a systematic review and meta-analysis of clinical trials and biological studies. Neuropsychopharmacology 2018;43:534-45.
82. Cooper RE, Tye C, Kuntsi J et al. Omega-3 polyunsaturated fatty acid supplementation and cognition: a systematic review and meta-analysis. J Psychopharmacol 2015;29:753-63.
83. Rapaport MH, Nierenberg AA, Schettler PJ et al. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Mol Psychiatry 2016;21:71-9.
84. Jiang W, Whellan DJ, Adams KF et al. Long-chain omega-3 fatty acid supplements in depressed heart failure patients: results of the OCEAN trial. JACC Heart Fail 2018;6:833-43.
85. Pawełczyk T, Grancow-Grabka M, Kotlicka-Antczak M et al. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res 2016;73:34-44.
86. Robinson DG, Gallego JA, John M et al. A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone. Schizophr Res 2019;204:295-303.
87. Pawełczyk T, Piatkowska-Janko E, Bogorodzki P et al. Omega-3 fatty acid supplementation may prevent loss of gray matter thickness in the left parieto-occipital cortex in first episode schizophrenia: a secondary outcome analysis of the OFFER randomized controlled study. Schizophr Res 2018;195:168-75.
88. Firth J, Rosenbaum S, Ward PB et al. Adjunctive nutrients in first-episode psychosis: a systematic review of efficacy, tolerability and neurobiological mechanisms. Early Interv Psychiatry 2018;12:774-83.
89. Farah A. The role of L-methylfolate in depressive disorders. CNS Spectr 2009;14:2-7.
90. Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry 2009;70:12-7.
91. Roffman JL, Petruzzi LJ, Tanner AS et al. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry 2018;23:316-22.
92. Kakar MS, Jehangir S, Mustafa M et al. Therapeutic efficacy of combination therapy of l-methylfolate and escitalopram in depression. Pak Armed Forces Med J 2017;67:976-81.
93. Rainka M, Aladeen T, Westphal E et al. L-methylfolate calcium in adolescents and children: a retrospective analysis. Presented at the Annual Meeting of the American Academy of Neurology, Los Angeles, April 2018.
94. Breier A, Liffick E, Hummer TA et al. Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders. Schizophr Res 2018;199:395-402.
95. Yolland CO, Phillipou A, Castle DJ et al. Improvement of cognitive function in schizophrenia with N-acetylcysteine: a theoretical review. Nutr Neurosci (in press).
96. Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci 2011;36:78-86.
97. Moghaddam B, Javitt DJN. From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology 2012;37:4-15.
98. Zhang HX, Hyrc K, Thio LL. The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine. J Physiol 2009;587:3207-20.
99. Slyepchenko A, Maes M, Jacka FN et al. Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities. Psychother Psychosom 2017;86:31-46.
100. Zheng P, Zeng B, Zhou C et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry 2016;21:786-96.
101. Cheung SG, Goldenthal AR, Uhlemann A-C et al. Systematic review of gut microbiota and major depression. Front Psychiatry 2019;10:34.
102. Kao A, Safarikova J, Marquardt T et al. Pro-cognitive effect of a prebiotic in psychosis: a double blind placebo controlled cross-over study. Schizophr Res 2019;208:460-1.
103. Liu NH, Daumit GL, Dua T et al. Excess of mortality in person with severe mental disorders: a multilevel intervention framework and priorities for clinical practice, policy and research agendas. World Psychiatry 2017;16:30-40.
104. Reedy J, Krebs-Smith SM, Miller PE et al. Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults. J Nutr 2014;144:881-9.
105. Teasdale SB, Ward PB, Rosenbaum S et al. Solving a weighty problem: systematic review and meta-analysis of nutrition interventions in severe mental illness. Br J Psychiatry 2017;210:110-8.
106. Firth J, Marx W, Dash S et al. The effects of dietary improvement on symptoms of depression and anxiety: a meta-analysis of randomized controlled trials. Psychosom Med 2019;8:265-80.
107. Rucklidge JJ, Kaplan BJ. Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity disorder: rationale and evidence to date. CNS Drugs 2014;28:775-85.
108. Sarris J, Byrne GJ, Stough C et al. Nutraceuticals for major depressive disorder – more is not merrier: an 8-week double-blind, randomised, controlled trial. J Affect Disord 2019;245:1007-15.
109. Berk M, Turner A, Malhi GS et al. A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. BMC Med 2019;17:18.
110. Shelton RC, Pencina MJ, Barrentine LW et al. 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 2015;76:1635-41.