The aim of this study is to evaluate the efficacy of N-acetylcysteine (NAC) add-on to antidepressant medication in treating patients who do not relieve during standard antidepressant treatment for 6 weeks at least. Meanwhile, secondary outcomes will include changes in some biomarkers and on specifically local brain activity (functional Magnetic Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). The hypothesis of this study is that NAC has positive effects on refractory major depressive disorder patients with increased inflammatory activity.
It's a double-blind randomised placebo controlled antidepressant augmentation study with 12-week treatment and 8-week follow up. Its purpose is to investigate antidepressant efficacy and safety of NAC in patients with treatment resistant depression (TRD) defined as insufficient response to 1 or more antidepressants given for at least 6 weeks and in an adequate dose, displaying increased peripheral inflammatory activity and moderate to severe depression. Apart from studying the effects of NAC on depression severity, the secondary outcomes are to examine a range of biomarkers related to potentially important underlying mechanisms such as oxidative stress and inflammatory activity and to evaluate the effects on brain functioning (fMRI) and on white matter integrity (DTI). Scale assessments are performed in the week preceding initiation of treatment, during the treatment period, at the end of the treatment period and at 8-week follow up. Neuro-imaging is performed before the treatment starts and in week 12, before the study medication is terminated. Collection of blood and morning urine only takes place at three time points, in the week preceding initiation of treatment, closely before tapering off the study medication and at the end of 8-week follow up. This study is hoped to show that NAC perform positive effects on those aspects mentioned above.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Participants of interventional group receive 1000mg N-acetylcysteine twice daily for 12 weeks.
Participants of placebo group receive placebo comparator matching with N-acetylcysteine twice daily for 12 weeks.
Tianjin Anding Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGThe change from baseline Hamilton Depression Rating Scale (HAMD)-17 items at week2,4,6,8,10,and 12.
The main objective is to investigate whether daily oral NAC administration in addition to regular treatment with an antidepressant will alleviate the severity of MDD symptoms as measured with the HAMD-17 after 12 weeks of treatment compared to placebo addition, and we also look at other time points, such as week 2,4,6,8,and 10.
Time frame: baseline, Week 2,4,6,8,10, and 12
The change from baseline HAMD-17 items at week14,16,18,and 20.
We also look at whether daily oral NAC treatment will still have measurable effects on HAMD-17 score at 8 weeks follow-up after discontinuation of NAC treatment.
Time frame: baseline, Week 14,16,18,and 20.
The effects of augmentation treatment with NAC on scores in Beck Anxiety Inventory (BAI)
Time frame: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on scores in Inventory of Depressive Symptoms-Self-Rated (IDS-SR)
Time frame: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on scores in WHO Disability Assessment Schedule Ⅱ (WHODAS-Ⅱ)
Time frame: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on scores in Montreal Cognitive Assessment (MoCA)
Time frame: baseline, Week 4,8,12,16,and 20.
The effects of augmentation treatment with NAC on local brain activity (fMRI and DTI)
Time frame: baseline, the end of week 12.
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Enrollment
200
The effects of augmentation treatment with NAC on a range of biomarkers representing the alleged underlying pathophysiological mechanisms
biomarkers associated with inflammation, oxidative stress, and neurogenesis in sample of serum and urine.
Time frame: baseline, the end of the week 12 and 20
Assessments the side effects measured with Checklist of 52 Somatic Items (CSI)
Time frame: baseline, Week 4,8,12,16,and 20.