Putative neuroprotective pharmacotherapies to target the staged progression of mental illness.
Study Goal
The researchers aimed to evaluate N-Acetylcysteine's potential as a neuroprotective agent in neuropsychiatric disorders by examining its mechanisms and clinical efficacy.
Results Summary
N-Acetylcysteine was found to inhibit pathways of neuroprogression, such as oxidative stress and inflammatory gene expression, and showed potential in preventing neural damage or cognitive decline. However, definitive clinical efficacy remains to be confirmed.
Population
Patients with neuropsychiatric disorders (e.g., depression, bipolar disorder, schizophrenia).
Effective Dosage
Not specified
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
lithium | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #1 |
second generation antipsychotics | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #2 |
antidepressants | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #3 |
minocycline | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #4 |
aspirin | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #5 |
cyclooxygenase-2 inhibitors | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #6 |
statins | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #7 |
ketamine | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #8 |
alpha-2-delta ligands | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #9 |
erythropoietin | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #10 |
oestrogen | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #11 |
leptin | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #12 |
N-acetylcysteine | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #13 |
curcumin | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #14 |
melatonin | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #15 |
ebselen | decrease | inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling | - | - | inhibit | #16 |
the agents reviewed | decrease | neural damage or loss, relapse or cognitive/functional decline | - | - | demonstrate clinical efficacy in preventing | #17 |
AIM: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential. METHOD: Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin. RESULTS: Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants; other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands; and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen. CONCLUSIONS: Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.