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The Efficacy of Adjunctive N-Acetylcysteine in Major Depressive Disorder: A Double-Blind, Randomized, Placebo-Controlled Trial
Open accessAbstract
OBJECTIVE: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression. METHOD: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. RESULTS: The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F₁,₅₂₀.₉ = 1.98, P = .067), and the groups did not separate at week 12 (t₃₆₀.₃ = -1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t₂₂₁.₀₃ = -2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. CONCLUSIONS: Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary. TRIAL REGISTRATION: www.anzctr.org.au Identifier: ACTRN12607000134426.
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“There is some evidence that NAC has clinical efficacy in unipolar depression and bipolar disorder.18,19”
From N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study (2015) · cites this paper as [19]
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“In addition, some studies showed that NAC could improve OCD-related trichotillomania (pathological nail-biting and skin-picking) [279].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [279]
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Cites
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
The assessment of anxiety states by rating
HAMILTON, M. (1959) · British Journal of Medical Psychology · doi:10.1111/j.2044-8341.1959.tb00467.x · Cited by 11,455
No adjustments are needed for multiple comparisons.
Rothman, K. J. (1990) · Epidemiology · doi:10.1097/00001648-199001000-00010 · Cited by 5,965
The mini international neuropsychiatric interview
Lecrubier, Y., Sheehan, D. V., Hergueta, T., & Weiller, E. (1998) · European Psychiatry · doi:10.1016/s0924-9338(99)80239-9 · Cited by 5,899
Yatham, L. N., & Malhi, G. S. (2011) · Oxford University Press eBooks · doi:10.1093/med/9780199562305.001.0001 · Cited by 3,515
Self-citationKirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050045 · Cited by 2,442
(1993) · PubMed · Cited by 1,900
Keller, M. B. (1987) · Archives of General Psychiatry · doi:10.1001/archpsyc.1987.01800180050009 · Cited by 1,643
Revising axis V for DSM-IV: a review of measures of social functioning
Goldman, H. H., Skodol, A. E., & Lave, T. R. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.9.1148 · Cited by 1,408
Research works printed but not linked: 2
- [12]12. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
- [24]24. International conference on harmonisation: guidance on statistical principles for clinical trials (ICH-E9). http://www.fda.gov/downloads/ drugs/guidancecomplianceregulatoryinformation/guidances/ucm073137. pdf. Updated September 1998. Accessed March 31, 2014.
Cited by
Sorted by citations
Malhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842
Self-citationN-Acetylcysteine (NAC): Impacts on Human Health
Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M. D., & Goulart, M. O. F. (2021) · Antioxidants · doi:10.3390/antiox10060967 · Cited by 526
Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review
Deepmala, Slattery, J., Kumar, N., Delhey, L., Berk, M., Dean, O., Spielholz, C., & Frye, R. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.015 · Cited by 463
Self-citationMarkers of Oxidative Stress and Neuroprogression in Depression Disorder
Vaváková, M., Ďuračková, Z., & Trebatická, J. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/898393 · Cited by 324
“Major depression is associated with imbalance between several components, including neuroprogressive and neuroprotective factors (lowered concentration of BDNF [24], NF𝜅B [38], and 5-HT [5]; elevated concentration of NO [27]), antioxidants and prooxidants (increased activity of XO [35] and catalase [39], decreased act…”
BackgroundInfluentialBerk, M., Köhler‐Forsberg, O., Turner, M., Penninx, B. W. J. H., Wrobel, A., Firth, J., Loughman, A., Reavley, N. J., McGrath, J. J., Momen, N. C., et al. (2023) · World Psychiatry · doi:10.1002/wps.21110 · Cited by 336
Self-citationRaghu, G., Berk, M., Campochiaro, P. A., Jaeschke, H., Marenzi, G., Richeldi, L., Wen, F., Nicoletti, F., & CALVERLEY, P. M. A. (2020) · Current Neuropharmacology · doi:10.2174/1570159x19666201230144109 · Cited by 318
“A placebo-controlled trial in 252 patients with major depressive disorder who were randomized to 12-weeks’ NAC or placebo added to standard antidepressant treatment, and followed up to 16 weeks, found no significant differences in depressive symptoms assessed using the Montgomery-Ǻsberg Depression Rating Scale (MADRS)…”
MethodSelf-citationThe many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders
Morris, G., & Berk, M. (2015) · BMC Medicine · doi:10.1186/s12916-015-0310-y · Cited by 245
“Given such a relationship, it is not surprising that antioxidant compounds are being trialed as potential antidepressant treatments [310,311].”
BackgroundSelf-citationNutritional Psychiatry: Where to Next?
Jacka, F. N. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.02.020 · Cited by 273
“, 2008a,b), but not in major depressive disorder (Berk et al., 2014).”
BackgroundUhl, G. R., Koob, G. F., & Cable, J. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13989 · Cited by 286
Bai, S., Guo, W., Feng, Y., Deng, H., Li, G., Nie, H., Guo, G., Yu, H., Ma, Y., Wang, J., et al. (2020) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-320912 · Cited by 235
Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs
Dale, E., Bang‐Andersen, B., & Sánchez, C. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.03.011 · Cited by 247
Yang, X. F., Wang, Y., Li, Q., Zhong, Y., Chen, L., Du, Y., He, J., Liao, L., Xiong, K., Yi, C., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00186 · Cited by 214
The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder
Maurya, P. K., Noto, C. D. S., Rizzo, L. B., Rios, A. C., Nunes, S. O. V., Barbosa, D. S., Sethi, S., Zeni‐Graiff, M., Mansur, R. B., Maes, M. H. J., et al. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.08.016 · Cited by 174
Ketamine and other glutamate receptor modulators for depression in adults
Caddy, C., Amit, B. H., McCloud, T. L., Rendell, J. M., Furukawa, T. A., McShane, R., Hawton, K., & Cipriani, A. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011612.pub2 · Cited by 174
Targeting classical IL-6 signalling or IL-6 trans-signalling in depression?
Maes, M., Anderson, G., Kubera, M., & Berk, M. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.888417 · Cited by 140
Self-citationThe role of mitochondria in mood disorders: from physiology to pathophysiology and to treatment
Giménez-Palomo, A., Dodd, S., Anmella, G., Carvalho, A. F., Scaini, G., Quevedo, J., Pacchiarotti, I., Vieta, E., & Berk, M. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.546801 · Cited by 140
Self-citationLeaky brain in neurological and psychiatric disorders: Drivers and consequences
Morris, G., Fernandes, B. S., Puri, B. K., Walker, A. J., Carvalho, A. F., & Berk, M. (2018) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867418796955 · Cited by 145
Self-citationAnti-inflammatory treatments for mood disorders: Systematic review and meta-analysis
Husain, M. I., Strawbridge, R., Stokes, P. R., & Young, A. H. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117725711 · Cited by 139
“However a more recent study with a larger sample size did not find any significant improvement in symptoms following treatment with NAC in MDD (Berk et al., 2014).”
BackgroundMitochondrial dysfunction: A fatal blow in depression
Song, Y., Cao, H., Zuo, C., Gu, Z., Huang, Y., Miao, J., Fu, Y., Guo, Y., Jiang, Y., & Wang, F. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115652 · Cited by 141
The renin–angiotensin system: a possible new target for depression
Vian, J., Pereira, C. L., Chavarria, V., Köhler, C. A., Stubbs, B., Quevedo, J., Kim, S., Carvalho, A. F., Berk, M., & Fernandes, B. S. (2017) · BMC Medicine · doi:10.1186/s12916-017-0916-3 · Cited by 136
Self-citationCell Death Pathways: a Novel Therapeutic Approach for Neuroscientists
Morris, G., Walker, A. J., Berk, M., Maes, M. H. J., & Puri, B. K. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0793-y · Cited by 134
Self-citationN-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects
Minarini, A., Ferrari, S., Galletti, M., Giambalvo, N., Perrone, D., Rioli, G., & Galeazzi, G. M. (2016) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1251580 · Cited by 126
“[50] MDD 2000 mg + TAU 252 Double-blind placebo controlled trial No significant effect on MADRS, response rate, remission rate at 12 week but significant effect at 16 week; LIFE-RIFT improved at 12 week; no significant change in GAF and SOFAS Carvalho et al.”
Integrating Early Intervention for Borderline Personality Disorder and Mood Disorders
Chanen, A. M., Berk, M., & Thompson, K. (2016) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000105 · Cited by 107
Self-citationInflammation as a treatment target in mood disorders: review
Jones, B. D. M., Daskalakis, Z. J., Carvalho, A. F., Strawbridge, R., Young, A. H., Mulsant, B. H., & Husain, M. I. (2020) · BJPsych Open · doi:10.1192/bjo.2020.43 · Cited by 106
Cognitive Dysfunction in Depression – Pathophysiology and Novel Targets
Carvalho, A., Miskowiak, K., Hyphantis, T., Kohler, C., Alves, G., Bortolato, B., G. Sales, P., Machado-Vieira, R., Berk, M., & McIntyre, R. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666141130203627 · Cited by 107
Self-citationBalmus, I. M., Ciobica, A., Antioch, I., Dobrin, R., & Timofte, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3975101 · Cited by 103
“In addition, some studies showed that NAC could improve OCD-related trichotillomania (pathological nail-biting and skin-picking) [279].”
ResultN-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence
Ooi, S. L., Green, R., & Pak, S. C. (2018) · BioMed Research International · doi:10.1155/2018/2469486 · Cited by 99
Lener, M. S., & Iosifescu, D. V. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12759 · Cited by 101
Brand, S., Moller, M., & Harvey, B. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150307004545 · Cited by 95
“In their clinical study, Berk and colleagues noted only limited support for the role of antioxidant and glutathione precursor, N-acetyl cysteine (NAC), as an adjunctive therapy for MD, although further such clinical studies are required [379].”
BackgroundResultN-acetylcysteine prevents stress-induced anxiety behavior in zebrafish
Mocelin, R., Herrmann, A. P., Marcon, M., Rambo, C. L., Rohden, A., Bevilaqua, F., de Abreu, M. S., Zanatta, L. C. B., Elisabetsky, E., Barcellos, L. J. G., et al. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.08.006 · Cited by 87
Immune-based strategies for mood disorders: facts and challenges
Colpo, G. D., Leboyer, M., Dantzer, R., Trivedi, M. H., & Teixeira, A. L. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2018.1407242 · Cited by 93
“A 12-week RCT study with MDD patients reported that NAC was not superior to placebo [125].”
BackgroundBhatti, J. A., Nascimento, B., Akhtar, U., Rhind, S. G., Tien, H. C. N., Nathens, A. B., & da Luz, L. T. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2017.00744 · Cited by 86
“Additionally, a few clinical trials have evaluated NAC targeting neurological diseases, including autism (24), major depression and other psychiatry conditions (9, 25, 26), neonatal asphyxia (27), and neurodegenerative disease (28).”
BackgroundNasir, M., Trujillo, D., Levine, J. L. S., Dwyer, J. B., Rupp, Z. W., & Bloch, M. H. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.548505 · Cited by 94
“However, when anxiety symptoms were analyzed in placebo-controlled trials looking at major depressive disorder (154) and trichotillomania (155), no significant differences were found in anxiety scores as measured by Hamilton Anxiety Rating Scale (HAM-A).”
MethodThe Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders
Bradlow, R. C. J., Berk, M., Kalivas, P. W., Back, S. E., & Kanaan, R. A. (2022) · CNS Drugs · doi:10.1007/s40263-022-00907-3 · Cited by 87
“They also found significant improvement in the functioning measures of Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) and Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE-LIFE) [79].”
BackgroundMethodInfluentialSelf-citationZheng, W., Zhang, Q. ‐., Cai, D., Yang, X.-H., Qiu, Y., Ungvari, G. S., Ng, C. H., Berk, M., Ning, Y., & Xiang, Y. (2018) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12862 · Cited by 83
“One RCT (30) examined the efficacy and safety of adjunctive NAC for MDD as measured by the MADRS.”
BackgroundMethodSelf-citationNamba, M. D., Leyrer-Jackson, J. M., Nagy, E. K., Olive, M. F., & Neisewander, J. L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.650785 · Cited by 76
Methamphetamine induced neurotoxic diseases, molecular mechanism, and current treatment strategies
Shrestha, P., Katila, N., Lee, S., Seo, J. H., Jeong, J., & Yook, S. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113591 · Cited by 91
Visentin, A. P. V., Colombo, R., Scotton, E., Fracasso, D. S., Rosa, A. R., Branco, C. S., & Salvador, M. M. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2972968 · Cited by 77
Dean, O. M., Gray, K. M., Villagonzalo, K.-A., Dodd, S., Mohebbi, M., Vick, T., Tonge, B. J., & Berk, M. (2016) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867416652735 · Cited by 78
“Specifically, we selected 500 mg/day based on the adult dose of 2000 mg/day being effective in our previous trials of NAC in psychiatry, over a similar treatment period (Berk et al., 2008a, 2008b, 2014) and with no reliable information on the safety profile of NAC in children.”
MethodSelf-citationMorris, G., Reiche, E. M. V., Murru, A., Carvalho, A. F., Maes, M. H. J., Berk, M., & Puri, B. K. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0843-5 · Cited by 75
Self-citationImmuno-psychiatry: an agenda for clinical practice and innovative research
Leboyer, M., Berk, M., Yolken, R. H., Tamouza, R., Kupfer, D. J., & Groc, L. (2016) · BMC Medicine · doi:10.1186/s12916-016-0712-5 · Cited by 74
Self-citationGlutamate transport: a new bench to bedside mechanism for treating drug abuse
Spencer, S., & Kalivas, P. W. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx050 · Cited by 71
Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review
Rosenblat, J. D., McIntyre, R. S., Alves, G. S., Fountoulakis, K. Ν., & Carvalho, A. F. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150630175044 · Cited by 72
“The endpoint of the study was 12 weeks, thus making it a negative trial, however, the delayed effect may suggest a latency of effect or potential preventative mechanism of further damage [79].”
BackgroundRossetti, A. C., Paladini, M. S., Riva, M. A., & Molteni, R. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107520 · Cited by 73
N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study
Prado, E., Maes, M., Piccoli, L. G., Baracat, M., Barbosa, D. S., Franco, O., Dodd, S., Berk, M., & Vargas Nunes, S. O. (2015) · Redox Report · doi:10.1179/1351000215y.0000000004 · Cited by 69
Self-citationHoepner, C. T., McIntyre, R. S., & Papakostas, G. I. (2021) · Nutrients · doi:10.3390/nu13030767 · Cited by 76
“Study Design Size Efficacy Safety Berk et al. 2014.”
BackgroundInfluentialN‐acetylcysteine as a new prominent approach for treating psychiatric disorders
Smaga, I., Frankowska, M., & Filip, M. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15456 · Cited by 73
“No significant improvement in depressive symptoms was observed at week 12; however, a significant effect appeared 4 weeks after treatment discontinuation (at week 16) (Berk et al., 2014).”
BackgroundTherapeutic potential of glutathione-enhancers in stress-related psychopathologies
Zalachoras, I., Hollis, F., Ramos‐Fernández, E., Trovò, L., Sonnay, S., Geiser, E., Preitner, N., Steiner, P., Sandi, C., & Morató, L. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.015 · Cited by 69
Mokoena, M. L., Harvey, B. H., Viljoen, F. P., Ellis, S. M., & Brink, C. B. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3928-8 · Cited by 65
“…N-acetyl cysteine (NAC) has been shown to display antidepressant effects as an augmentation strategy in bipolar disorder (Berk et al. 2008), while a recent study has provided some albeit limited support for its efficacy as adjunctive therapy in patients with unipolar depression (Berk et al. 2014).”
ResultTargeting the immune system in the treatment of bipolar disorder
Rosenblat, J. D. (2019) · Psychopharmacology · doi:10.1007/s00213-019-5175-x · Cited by 64
Fernandes, J., & Gupta, G. L. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.025 · Cited by 64
“Intriguingly, the beneficial roles of NAC in depression pathogenesis have also been reported clinically [34], nonsuicidal self-injury adolescents and young adults [35].”
Mohebbi, M., Dodd, S., Dean, O. M., & Berk, M. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.05.006 · Cited by 60
“Study 2 was a randomized, double-blind, placebo-controlled, parallel-design study to evaluate the efficacy of 1 g/day NAC for major depressive disorder (MDD) in addition to existing treatments [17].”
MethodSelf-citationNaumenko, V. S., Kulikov, A. V., Kondaurova, E. M., Tsybko, A. S., Kulikova, E. A., Krasnov, I. B., Shenkman, E. A., Sychev, V. N., Bazhenova, E. Y., Sinyakova, N. A., et al. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.045 · Cited by 59
“Disturbances of apoptosis in the adult brain lead to severe psychopathology such as depression (Berk et al., 2014; Garcia-Fuster et al., 2014), learning and memory deficit (Szewczyk, 2013), Parkinson’s (Barbiero et al., 2014) and Alzheimer’s (Tang et al., 2014) diseases.”
BackgroundClark, R. S. B., Empey, P. E., Bayır, H., Rosario, B. L., Poloyac, S. M., Kochanek, P. M., Nolin, T. D., Au, A. K., Horvat, C. M., Wisniewski, S. R., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180280 · Cited by 59
Mocelin, R., Marcon, M., D’ambros, S., de Mattos, J. N., Sachett, A., Siebel, A. M., Herrmann, A. P., & Piato, Â. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1165-y · Cited by 64
Réus, G. Z., dos Santos, M. A. B., Abelaira, H. M., Titus, S. E., Carlessi, A. S., Matias, B. I., Bruchchen, L., Florentino, D., Vieira, A. A. D. S., Petronilho, F. C., et al. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2732 · Cited by 57
“In patients with MDD, treatment with NAC showed superior efficacy to placebo after 16 weeks [30].”
MethodUmehara, H., Numata, S., Watanabe, S., Hatakeyama, Y., Kinoshita, M., Tomioka, Y., Nakahara, K., Nikawa, T., & Ohmori, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-05121-6 · Cited by 56
Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder
Jembrek, M. J., Oršolić, N., Karlović, D., & Peitl, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086888 · Cited by 58
Döme, P., Tombor, L., Lazáry, J., Gonda, X., & Rihmer, Z. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.12.015 · Cited by 49
“3% of the total sample did not receive any psychotropics) (Berk et al., 2014).”
Du, Y., Dou, Y., Wang, M., Wang, Y., Yan, Y., Fan, H., Fan, N., Yang, X., & Ma, X. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1407529 · Cited by 57
Role of Oxidative Stress and Ca2+ Signaling in Psychiatric Disorders
Nakao, A., Matsunaga, Y., Hayashida, K., & Takahashi, N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.615569 · Cited by 51
“(Berk et al., 2014) Adjunctive NAC 2,000 mg/day supplements NAC: 135”
MethodMethylene blue and its analogues as antidepressant compounds
Delport, A., Harvey, B. H., Petzer, A., & Petzer, J. P. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0081-6 · Cited by 46
“Importantly, altered antioxidant enzyme activity, lipid peroxidation and oxidative and nitrosative stress in depressed patients may be normalized by antidepressants (Bilici et al. 2001), while adjunctive antioxidant therapy may offer beneficial effects (Berk et al. 2014).”
BackgroundOberholzer, I., Möller, M., Holland, B. J., Dean, O. M., Berk, M., & Harvey, B. H. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0144-8 · Cited by 46
Self-citationDean, R. L., Hurducas, C., Hawton, K., Spyridi, S., Cowen, P. J., Hollingsworth, S., Marquardt, T., Barnes, A., Smith, R., McShane, R., et al. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011612.pub3 · Cited by 95
Hang, X., Zhang, Y., Li, J., Li, Z., Zhang, Y., Ye, X., Tang, Q., & Sun, W. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.691200 · Cited by 44
N -Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study
Cullen, K. R., Klimes‐Dougan, B., Schreiner, M. W., Carstedt, P. A., Marka, N. A., Nelson, K. J., Miller, M. J., Reigstad, K. M., Westervelt, A., Gunlicks‐Stoessel, M., et al. (2017) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2017.0032 · Cited by 40
“For example, Berk et al. (2014) noted that NAC was associated with clinical improvement in some of the secondary measures such as overall functioning and quality of life.”
BackgroundCorticostriatal circuitry in regulating diseases characterized by intrusive thinking
Kalivas, B. C., & Kalivas, P. W. (2016) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2016.18.1/pkalivas · Cited by 43
Kishi, T., Miyake, N., Okuya, M., Sakuma, K., & Iwata, N. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05629-2 · Cited by 39
“Finally, seven fixed-dose DBRPCTs including 728 participants were included in the current systematic review and meta-analysis (Bauer et al. 2018; Berk et al. 2008, 2012, 2014, 2019, 2019; Porcu et al. 2018).”
BackgroundThe use of statins for the treatment of depression in patients with acute coronary syndrome
Kim, S. W., Bae, K., Kim, J.-M., Shin, I., Hong, Y. J., Ahn, Y., Jeong, M. H., Berk, M., & Yoon, J. S. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.116 · Cited by 38
Self-citationBehavioral and Biochemical Effects of N-Acetylcysteine in Zebrafish Acutely Exposed to Ethanol
Mocelin, R., Marcon, M., D’ambros, S., Herrmann, A. P., Araújo, A. S. D. R., & Piato, Â. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2442-2 · Cited by 40
Hasebe, K., Gray, L. J., Bortolasci, C. C., Panizzutti, B., Mohebbi, M., Kidnapillai, S., Spolding, B., Walder, K. R., Berk, M., Malhi, G. S., et al. (2017) · Acta Neuropsychiatrica · doi:10.1017/neu.2017.2 · Cited by 37
“The biological samples were collected at baseline and the end of treatment (week 12) (17).”
BackgroundMethodResultInfluentialSelf-citationKim, S., Kang, H., Bae, K., Shin, I., Hong, Y. J., Ahn, Y., Jeong, M. H., Berk, M., Yoon, J., & Kim, J. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.07.003 · Cited by 37
Self-citationIt is time to investigate integrative approaches to enhance treatment outcomes for depression?
Lopresti, A. L. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.03.008 · Cited by 40
“ylcysteine was confirmed in a meta-analysis to effectively lower depressive symptoms in adults with depression compared to a placebo [63] but had limited effects as an adjunct to antidepressants [64].”
Ornoy, A., Becker, M., Weinstein‐Fudim, L., & Ergaz, Z. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103721 · Cited by 37
Rosenblat, J. D., Gregory, J. M., Carvalho, A. F., & McIntyre, R. S. (2016) · Current Molecular Medicine · doi:10.2174/1566524016666160126144303 · Cited by 34
Schiavone, S., & Trabace, L. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.03.019 · Cited by 36
Yang, C., Bosker, F. J., Li, J., & Schoevers, R. A. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1845-1 · Cited by 34
Drug repurposing may generate novel approaches to treating depression
Ebada, M. E. (2017) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12815 · Cited by 36
Yang, L., Zheng, L., Wan, Y., Chen, Z., Li, P., & Wang, Y. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00696 · Cited by 33
RetractedN-acetylcysteine (NAC) for methamphetamine dependence: A randomised controlled trial
McKetin, R., Dean, O. M., Turner, A., Kelly, P. J., Quinn, B., Lubman, D. I., Dietze, P., Carter, G. L., Higgs, P., Sinclair, B., et al. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.101005 · Cited by 33
Self-citationDo Statins Have Antidepressant Effects?
Köhler-Forsberg, O., Gasse, C., Berk, M., & Østergaard, S. D. (2017) · CNS Drugs · doi:10.1007/s40263-017-0422-3 · Cited by 31
“Several drugs that are primarily used due to their antiinflammatory effects have shown antidepressant effects as well, including aspirin [10, 60], other non-steroidal antiinflammatory drugs (NSAIDs; especially celecoxib [5, 61]), minocycline [62], monoclonal antibodies [63], pioglitazone, N-acetylcysteine and curcumin…”
Self-citationDrug repositioning for treatment-resistant depression: Hypotheses from a pharmacogenomic study
Fabbri, C., Kasper, S., Zohar, J., Souery, D., Montgomery, S., Albani, D., Forloni, G., Ferentinos, P. P., Rujescu, D., Mendlewicz, J., et al. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110050 · Cited by 36
Ayala, T. B., Ortega, D. R., Rodríguez, P. O., Pineda, B., de la Cruz, G. P., González‐Esquivel, D. F., Schwarcz, R. M., Sathyasaikumar, K. V., Jiménez‐Anguiano, A., & de la Cruz, V. P. (2021) · Antioxidants · doi:10.3390/antiox10020147 · Cited by 30
Yusuf, M., Khan, M., Robaian, M. A., & Khan, R. A. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0250 · Cited by 32
“, 2008) and N-acetyl cysteine (NAC) (Berk et al., 2014) were found in MDD patients as low levels of CoQ10 is linked with higher concentrations of ROS, RNS and tumor necrosis factor alpha with mitochondrion dysfunctions.”
A potential role for N‐acetylcysteine in the management of methamphetamine dependence
McKetin, R., Dean, O. M., Baker, A., Carter, G. L., Turner, A., Kelly, P. J., & Berk, M. (2016) · Drug and Alcohol Review · doi:10.1111/dar.12414 · Cited by 32
“The possibility that NAC could alleviate psychiatric symptoms is supported by its broader efficacy with other neuropsychiatric disorders (bipolar disorder depression, autism, schizophrenia), with NAC showing particular efficacy for depression [44-47 , This article is protected by copyright.”
Self-citationNadeem, A., Siddiqui, N. M., Al-Harbi, N. O., Attia, S. M., AlSharari, S. D., & Ahmad, S. F. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.04.010 · Cited by 30
Morley, K. C., Baillie, A., van den Brink, W., Chitty, K. M., Brady, K. T., Back, S. E., Seth, D., Sutherland, G. T., Leggio, L., & Haber, P. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1501471 · Cited by 29
“Signals of efficacy have been reported in patients with more severe major depressive disorder [86], obsessive compulsive disorder [87], and also for reducing depressive symptoms in patients with bipolar disorder [88].”
BackgroundMemudu, A. E., Samson, P., & Itohan, O. R. (2020) · Metabolic Brain Disease · doi:10.1007/s11011-020-00556-9 · Cited by 34
Update on Statin Treatment in Patients with Neuropsychiatric Disorders
Avan, R., Sahebnasagh, A., Hashemi, J., Monajati, M., Faramarzi, F., Henney, N. C., Montecucco, F., Jamialahmadi, T., & Sahebkar, A. (2021) · Life · doi:10.3390/life11121365 · Cited by 34
Mood Therapeutics: Novel Pharmacological Approaches for Treating Depression
Henter, I. D., SOUSA, R. T. D., Gold, P. W., Brunoni, A. R., Zarate, C. A., & Machado‐Vieira, R. (2016) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2017.1253472 · Cited by 28
“In MDD, a large, 12-week, controlled, randomized, add-on trial of 252 patients found that those receiving NAC showed antidepressant improvements similar to the placebo group [111]; however, at week 12, scores on the Longitudinal Interval FollowUp Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from…”
MethodTomko, R. L., Baker, N. L., Hood, C. O., Gilmore, A. K., McClure, E. A., Squeglia, L. M., McRae‐Clark, A. L., Sonne, S. C., & Gray, K. M. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05384-z · Cited by 29
“Evidence for the inverse relation has also been demonstrated, where persons with MDD are more likely to subsequently use cannabis (Feingold et al. 2015) and to develop a CUD (Pacek et al. 2013).”
BackgroundInfluentialMartín‐Aragón, S., Villar, Á., & Benedı́, J. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.08.007 · Cited by 29
“For instance, N-acetyl-cysteine has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial (Berk et al., 2014).”
BackgroundAnxiolytic and anti-stress effects of acute administration of acetyl-L-carnitine in zebrafish
Pancotto, L., Mocelin, R., Marcon, M., Herrmann, A. P., & Piato, Â. (2018) · PeerJ · doi:10.7717/peerj.5309 · Cited by 27
Giakoumatos, C. I., & Osser, D. N. (2019) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000197 · Cited by 27
Chakraborty, S., Tripathi, S. J., Srikumar, B. N., Raju, T. R., & Rao, B. S. S. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104605 · Cited by 26
Thiol disulfide homeostasis in psychiatric disorders: A comprehensive review
Tunçay, M. E., Atagün, M. İ., & Erel, Ö. (2023) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110719 · Cited by 25
Scarr, E., Udawela, M., & Dean, B. (2019) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867419857808 · Cited by 24
“In BA 33, the impact of gene expression on glutathione redox reactions suggests that oxidative stress could be a component of the aetiology of MD and why treatment with antioxidants can lessen symptom severity (Berk et al., 2014).”
BackgroundChakraborty, S., Rao, S., & Tripathi, S. J. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110527 · Cited by 25
Delport, A., Harvey, B. H., Petzer, A., & Petzer, J. P. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00042 · Cited by 23
Sakai, M., Yu, Z., Taniguchi, M., Picotin, R., Oyama, N., Stellwagen, D., Ono, C., Kikuchi, Y., Matsui, K., Nakanishi, M., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043798 · Cited by 25
“Berk et al. found that NAC had limited efficacy as an adjunctive therapy for major depressive disorder (MDD) [19].”
BackgroundInfluential
Metadata
- Authors
- Berk, M., Dean, O. M., Cotton, S. M., Jeavons, S., Tanious, M., Kohlmann, K., Hewitt, K., Moss, K., Allwang, C., Schapkaitz, I., Robbins, J., Cobb, H., Ng, F., Dodd, S., Bush, A. I., & Malhi, G. S.
- Affiliations
- Barwon Health (AU)
- Deakin University (AU)
- Corresponding author
- Berk, Michael
- ORCID
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2014-06-15
- Volume
- 75
- Issue
- 06
- Pages
- 628-636
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2099204286
- Cited by
- 172
- References
- 49
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 10 · 2021: 15 · 2020: 18 · 2019: 14 · 2018: 23 · 2017: 21 · 2016: 16 · 2015: 19 · 2014: 2
- FWCI
- 14.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, N-acetylcysteine, adjunctive therapy, glutathione precursor, oxidative stress, neuroinflammation, glutamate, antidepressant efficacy, adverse events, Montgomery-Asberg Depression Rating Scale, depression pathogenesis, redox signaling, neurogenesis, apoptosis, monoamine hypothesis, newer antidepressants, treatment-resistant depression
- MeSH terms
- Acetylcysteine, Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Male, Middle Aged, Surveys and Questionnaires, Patient Satisfaction
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