Trial reportBMC psychiatry2018
N-acetylcysteine as add-on to antidepressant medication in therapy refractory major depressive disorder patients with increased inflammatory activity: study protocol of a double-blind randomized placebo-controlled trial.
Trial report in BMC psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02972398 (N-Acetyl Cysteine add-on to Antidepressant Medication in Therapy Refractory Major Depressive Disorder Patients With Increased Inflammatory Activity), which is not on this map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
N-Acetyl Cysteine add-on to Antidepressant Medication in Therapy Refractory Major Depressive Disorder Patients With Increased Inflammatory Activity
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- TNF-α levels in first-episode, drug-naïve patients with major depressive disorder: a case-control study and meta-analysis.BMC psychiatry · 2026Pooled it
- Depressive symptoms and cannabis use in a placebo-controlled trial of N-Acetylcysteine for adult cannabis use disorder.Psychopharmacology · 2020Trial
- Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target?Molecular neurobiology · 2026Review
- Article
- Neuroinflammation-A Crucial Factor in the Pathophysiology of Depression-A Comprehensive Review.Biomolecules · 2025Review
- Fibromyalgia, Depression, and Autoimmune Disorders: An Interconnected Web of Inflammation.Biomedicines · 2025Review
- Partial Response to Antidepressant Treatment: The Role of Nutraceutical Compounds.Clinical neuropsychiatry · 2023Article
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment.Neuropharmacology · 2023Review
- Urine 3-Nitrotyrosine and Serum HDL as Potential Biomarkers of Depression.Journal of clinical medicine · 2023Article
- Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression.Brain sciences · 2022Review
- Clinical translational neuroimaging of the antioxidant effect of N-acetylcysteine on neural microstructure.Magnetic resonance in medicine · 2022Article
- The associations of CNR1 SNPs and haplotypes with vulnerability and treatment response phenotypes in Han Chinese with major depressive disorder: A case-control association study.Molecular genetics & genomic medicine · 2021Article
- Review
- Identifying Biological Signatures of N-Acetylcysteine for Non-Suicidal Self-Injury in Adolescents and Young Adults.Journal of psychiatry and brain science · 2021Article
- Review
- Role of inflammation in depression relapse.Journal of neuroinflammation · 2019Review
- Antidepressant-Like Activity of MyelophilFrontiers in pharmacology · 2019Article
- The Efficacy of N-Acetyl-Cysteine (NAC) Supplementation in FST Model for Screening Antidepressants.Basic and clinical neuroscienceArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA subgroup of depressed patients with increased inflammatory activity was shown to be more susceptible to develop Treatment Resistant Depression (TRD). Earlier studies with anti-inflammatory drugs have shown benefits in the treatment of major depressive disorder (MDD), but the effects are expected to be higher in patients with increased inflammatory activity. Supplementation of N-acetylcysteine (NAC) to ongoing antidepressant therapy may positively influence outcome of depression treatment in these patients. Therefore, this study aims to investigate the efficacy of NAC supplementation in patients with insufficient response to standard antidepressant treatment, and to explore potential roles of inflammation and oxidative stress involved in the alleged pathophysiological processes of TRD. METHODS/
designA double-blind randomized placebo-controlled study comparing NAC versus placebo as add-on medication to antidepressant treatment with 12-week treatment and 8-week follow up in patients with TRD and increased inflammatory activity. Apart from clinical efficacy defined as the change in Hamilton Depression Rating Scale (HAMD)-17 score, secondary outcomes include changes in pathophysiological mechanisms related to depression as well as changes in local brain activity (functional Magnetic Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). Importantly, sole patients with CRP levels with values between 0.85 and 10 mg/L will be included. DISCUSSION: This is the first clinical trial taking both TRD and increased inflammatory activity as inclusion criteria. This study will provide reliable evidence for the efficacy of NAC in patients with TRD displaying increased inflammatory activity. And this study also will help explore further the roles of inflammation and oxidative stress involved in the alleged pathophysiological processes of TRD.
trial registrationThe trial protocol has been registered on "ClinicalTrials.gov"with protocol ID "NAC-2015-TJAH" and ClinicalTrials.gov ID " NCT02972398 ".
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.