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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NAC has clinical efficacy in unipolar depression and bipolar disorder.
“There is some evidence that NAC has clinical efficacy in unipolar depression and bipolar disorder.18,19”
From <i>N</i>-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study (2015) · cites this paper as [19]
Some studies showed that NAC could improve OCD-related trichotillomania (pathological nail-biting and skin-picking).
“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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“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 88 · see citing works
“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 89 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
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 78 · see citing works
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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 · see citing works
“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 74 · see citing works
Self-citationImmuno-psychiatry: an agenda for clinical practice and innovative research
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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 · see citing works
Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review
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“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 70 · see citing works
<i>N</i>-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study
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“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 · see citing works
“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 67 · see citing works
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“…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 63 · see citing works
Fernandes, J., & Gupta, G. L. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.025 · Cited by 64 · see citing works
“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 · see citing works
“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 58 · see citing works
“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 58 · see citing works
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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 · see citing works
“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 · see citing works
Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder
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“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 52 · see citing works
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 49 · see citing works
“(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 · see citing works
“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 44 · see citing works
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 · see citing works
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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 · see citing works
“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. (2016) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2016.18.1/pkalivas · Cited by 37 · see citing works
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“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 · see citing works
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 38 · see citing works
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 · see citing works
“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 · see citing works
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 37 · see citing works
“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].”
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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 33 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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 33 · see citing works
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 31 · see citing works
Yusuf, M., Khan, M., Robaian, M. A., & Khan, R. A. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0250 · Cited by 31 · see citing works
“, 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 30 · see citing works
“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 · see citing works
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“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 · see citing works
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 33 · see citing works
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 · see citing works
“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 28 · see citing works
“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 28 · see citing works
“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 · see citing works
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Thiol disulfide homeostasis in psychiatric disorders: A comprehensive review
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“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).”
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Delport, A., Harvey, B. H., Petzer, A., & Petzer, J. P. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00042 · Cited by 23 · see citing works
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 23 · see citing works
“Berk et al. found that NAC had limited efficacy as an adjunctive therapy for major depressive disorder (MDD) [19].”
BackgroundInfluential
- 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 › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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