N-acetylcysteine is known for its uses in non-psychiatric conditions, such as paracetamol overdose and as a mucolytic. The rationale for its administration in psychiatric conditions is based on its ability reducing synaptic glutamate release, which was found to be increased in the cerebrospinal fluid of OCD patients.

Evaluating N-acetylcysteine efficacy in OCD symptoms. Studying mechanisms underlying its action. Identifying the frequency of side effects.

PubMed database search, with the “N-acetylcysteine obsessive compulsive” keyword expression. The search was restricted to English-only articles, published in the last ten years. Twenty-five results among the best match correspondence were selected. Reference lists of articles were reviewed to identify additional articles.

Oliver et al. found that a daily dose of 2.400 to 3.000 milligrams of N-acetylcysteine reduced the severity of obsessive-compulsive symptoms with minimal side effects; Smith et al. found inconclusive evidence on its efficacy. A clinical trial from Ghazinadeh et al. revealed N-acetylcysteine to be effective as an add-on to citalopram, reducing the score of resistance/control to obsessions after supplementing with N-acetylcysteine. Costa et al. found out it was superior to placebo in anxiety control as a secondary outcome.

The potential efficacy of N-acetylcysteine in the treatment of psychiatric disorders attracted interest. Mixed evidence was found that N-acetylcysteine may have some benefits controlling compulsions, both as an adjunctive as and as monotherapy. Thus, larger and more robust studies are required to further investigate the clinical effectiveness of N-acetylcysteine in this area.

No significant relationships.

An increasing body of literature supports the hypothesis that immune imbalance towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this dysregulation, ameliorating the symptoms of schizophrenia. N-acetylcysteine exhibits anti-inflammatory properties and may regulate various neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation, becoming an interesting augmenting drug for schizophrenia treatment.

We aim to review the literature regarding the therapeutic effects of N-acetylcysteine in Schizophrenia.

We performed an updated review in the PubMed database using the terms “N-acetylcysteine” and “Schizophrenia”. The included articles were selected by title and abstract.

The literature suggests that N-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Also, this augmentation therapy seems to be beneficial in all illness stages

N-acetylcysteine appears to be a promising agent for augmenting conventional pharmacotherapy in schizophrenia, however, further research is needed to consolidate the current findings.

N-acetylcysteine (NAC) is a precursor of cysteine and glutathione, widely known as an antidote to paracetamol overdose. Its role as precursor of an antioxidant and modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways, raised interest in its application in psychiatric disorders. NAC emerges as a promising therapeutic agent in substance use disorders (SUD) and provides a treatment option in a field with limited and suboptimal therapies.

To describe the use of NAC in SUD (tobacco, cocaine, cannabis, methamphetamine and alcohol), its potential mechanisms and clinical application.

The literature was searched using the Pubmed database with the following keywords “N-acetylcysteine”, “Substance use disorders” and “Psychiatry”. Retrieved papers (2011-2018) were selected according to their relevance.

SUD results in disruption of glutamate system, in nucleus accumbens, a critical brain area in the rewarding system. NAC reestablishes glutamate homeostasis restoring function of the cysteine-glutamate exchange in glial cells and reversing the downregulated GLT-1 receptor. Concerning its properties, evidence suggests that NAC is able to decrease drive, craving or compulsion to consume, making it particular useful in relapse prevention after achieving abstinence.

NAC has revealed itself as a promising therapeutic agent in SUD and its safety profile and favourable tolerability, as well as being an over-the-counter medication, adds to its interest. Data is still preliminary for the use of NAC in psychiatry disorders, due to the relatively small number of trials and their heterogeneous methodology. Larger studies are needed to confirm efficacy, optimal doses, long-term tolerability and side effects.

The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).

This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.

In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).

Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs).

PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes.

Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06–0.54], estrogens (ES: 0.78; n = 723; CI 0.36–1.19), minocycline (ES: 0.40; n = 946; CI 0.11–0.68), and NAC (ES: 1.00; n = 442; CI 0.60–1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect.

Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.

This study aimed to explore effects of adjunctive N-acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression.

We embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum samples at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment.

NAC treatment significantly improved depressive symptoms on the Montgomery–Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment.

Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.

To investigate the use of systemic N-acetylcysteine and vitamin A in the prevention of gentamicin ototoxicity in rats.

Forty-two Wistar rats were divided into four groups according to treatment: intratympanic saline, intratympanic gentamicin, intraperitoneal vitamin A after intratympanic gentamicin, and intraperitoneal N-acetylcysteine after intratympanic gentamicin. Signal-to-noise ratio and distortion product otoacoustic emissions were evaluated in all groups.

N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 2, 3, 4 and 6 kHz, as determined by the distortion product otoacoustic emission measurements. According to the signal-to-noise measurements, N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 3, 6 and 8 kHz.

Gentamicin-induced hearing loss in rats may be prevented by the concomitant use of vitamin A and N-acetylcysteine. Specifically, N-acetylcysteine appeared to have a more protective effect than vitamin A for a greater range of noise frequencies.

To systematically review the efficacy and safety of N-acetylcysteine (NAC) for the prevention of radiocontrast-induced nephropathy (RIN), and to discuss its potential role in the emergency department.

We conducted a search of MEDLINE (from 1966 to December 2003), PubMed (1966 to December 2003) and EMBASE (1988 to December 2003) for English-language, prospective, randomized, controlled trials in humans using the search terms N-acetylcysteine, acetylcysteine, radiopharmaceuticals, contrast media, and kidney failure (acute).

Five trials support and 4 trials refute the hypothesis that NAC helps prevent RIN. In 7 of 9 trials, oral NAC was administered twice daily for 2 days, on the day before and on the day of the radiocontrast study — a regime not feasible for emergent situations. More recent trials suggest that adequate hydration and lower volumes of radiocontrast, rather than NAC, are more effective ways to prevent RIN.

Although further study may be indicated, current evidence does not suggest that NAC has a role in the emergency prevention of RIN.