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

Chenghao Yang, Fokko J Bosker, Jie Li, Robert A Schoevers, Chenghao Yang, Fokko J Bosker, Jie Li, Robert A Schoevers

Abstract

Background: A 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/design: A 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 registration: The trial protocol has been registered on "ClinicalTrials.gov"with protocol ID "NAC-2015-TJAH" and ClinicalTrials.gov ID " NCT02972398 ".

Keywords: Biomarkers; Brain activity; Inflammatory activity; N-acetylcysteine; Treatment resistant depression.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the medical ethics committee of Tianjin Anding Hospital. All participants need to sign informed consent about the content and extent of the planned study prior to the participations. The patients’ guardians will sign the informed consent on behalf of the participants when the capacity of participants to consent is compromised.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Trial flowchart. Eventually 200 patients will be required to finish the treatment study, being randomly divided into two groups including Trial arm 1 (antidepressant + NAC, n = 100) and Trial 2 (antidepressant + placebo, n = 100). For the fMRI scanning at baseline (week 0) and the 12th week, 50 patients will be included

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Source: PubMed

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