Study: N-Acetylcystein as an additional treatment for schizophrenia
Study: N-Acetylcystein as an additional treatment for schizophrenia
reference
rapado-castro M., Berk M., Venugopal K., Bush Ai, Dodd S., Dean Om. On the way to stage-specific treatments: effects of the duration of the disease on the therapeutic response to additional treatment with N-acetylcysteine in schizophrenia. Prog neuropsychopharmacol biiol Psychiatry . 2015; 3 (57): 69-75.
Design
A double-blind, placebo-controlled study for examining whether the duration of the illness was a factor in modulation of the reaction to N-Acetylcystein (NAC).
participant
The study included 121 participants, which randomized placebo (n = 62) or n-acetylcysteine (nac; n = 59) for 24 weeks. The participants had to meet the diagnostic criteria for schizophrenia (DSM-IV) and either have a positive and negative symptom score (PANSS) of ≥ 55 (range 30 to 100) or a Clinical Global Impression-Severity (CGI-S) score ≥ 1 to 7). Both inpatient and outpatient patients were eligible to participate. The participants currently had to take an antipsychotic. People who took a mood stabilizer (e.g. lithium, valproat, carbamepine) were excluded, as did those who are currently taking medication that are known to prevent a glutathional deficiency (500+ MG NAC, 200+ μg selenium per day or 500+). He vitamin E per day).
medication and dosage study
The participants received 2 NAC capsules (500 mg) (2 g per day) or suitable placebo capsules twice a day.
target parameter
The participants were based on a structured clinical interview (Mini International Neuropsychiatric Interview [Mini], DSM-IV) with various psychological assessment tools. Faded examiners, who were all experienced clinicians, carried out the reviews.
The effectiveness measurements were repeated every 2 weeks or on the day of the end of the study in the first 8 weeks if the participant left the study 8 weeks ago. After 8 weeks, the reviews were carried out every 4 weeks to 24 weeks when the treatment ended. 4 (± 2) weeks after completion, a follow -up examination was carried out after discontinuation to determine changes in the participant status.
The duration of the illness at the beginning of the course was divided into 20 years and compared with results measurements. Data from the same study cohort were first published in 2008.
important knowledge
A first analysis of this data in 2008 showed that the subjects dealt with with NAC during the total study period in the PANSS-total value improved more than the subjects treated with placebo ( p = 0.009), Panss negative ( p = 0.018) and Panss General ( p = 0 035). Improvements were also reflected in CGI-S ( p = 0.004) and CGI improvement ( p = 0.025) points. No significant change was found on the positive panss sub-scale. Treatment with NAC was also associated with an improvement in acathisia ( p = 0.022) in the first published study. The effect sizes at the end point matched with moderate advantages.
In this current article that analyzes the same data, but compares the duration of the disease with the result, "was found consistently between the treatment group and duration in positive symptoms. Variables (CGI): F2, 58 = 4.647; p = 0.035]. " In other words, the longer the patients suffered from schizophrenia, the more improvement they learned while taking Nac.
participants who were sick for 20 years or more, benefited the most from the treatment.
participants who were sick for 20 years or more, benefited the most from treatment.
These changes were not what the investigators had predicted. Their assumption was that NAC's effects would be greater in patients with the beginning of the illness. The results were opposite: the longer the history of the disease, the greater the address.
practice implications
These results are a pleasant and welcome surprise.
The hypothesis of this study was that people with schizophrenia would take more benefits from NAC in early stages; This idea has proven to be wrong. Instead, the longer the participants suffered from schizophrenia, the greater their benefits from taking NAC. We should note that these services only apply to the symptoms of the disease. NAC did not change the "extrapyramidal undesirable events in connection with treatment" (that is, the movement disorders through the long -term use of treatment medication); It only improved the symptoms of schizophrenia itself.
About 1.1 % of the general population suffer from schizophrenia 2 , but it has long been known that schizophrenia occurs in families. The risk of illness increases to 10 % for people who have a first degree relative with schizophrenia. For a identical twin of a person with schizophrenia, the risk increases to 40 % to 65 %.
NAC is obtained from the amino acid cysteine and is available as a dietary supplement that is advertised because of its antioxidant properties. Nac is well tolerated and safe; It has been widespread internationally for decades. 4 NAC is used as an antidote for paracetamol overdosing and has been approved by the FDA since 1985, either orally or intravenous.
NAC is also used as a mucolytic in chronic obstructive lung disease 6 and cystic fibrosis, 7 to protect the kidneys against damage caused by contrast medium that is used in imaging examinations, 8 and as a preventive remedy. Can be used to prevent and treat a seasonal influenza virus infection.
In the past 10 years, there has been more and more evidence that NAC is also useful in the treatment of psychiatric and neurological disorders. It seems to moderate pathophysiological processes that are involved in a number of psychiatric and neurological disorders, including oxidative stress, neurogenesis and apoptosis, mitochondrial dysfunction, neuroinflammation and dysregulation of glutamine and dopamine. and metaplasticity. 12 The neuroca adaptation theory of addiction suggests that exposure to abuse drugs causes adaptive molecular and cellular changes in the brain that convey addictive memories. Compared to other types of memories, addictive memories develop quickly and last extremely long; The cellular and molecular processes that convey addiction -related memories are exceptionally clever and efficient.
In recent years, numerous reports on the use of NAC to treat a series of psychiatric or neurological diseases, including schizophrenia, have been published; bipolar disorder; Skin picking; Trichotillomania; Oede of obsessive disorder; Autism; Gambling; Dependence on nicotine, cannabis, cocaine and methamphetamine; Epilepsy; Amyotrophic lateral sclerosis; Neuropathy; and traumatic brain trauma. 14-15
in a systematic review published in August 2015 on the use of NAC in psychiatry and neurology evaluated and classified Deepmala et al. the level of evidence at the time for the use of NAC in the treatment of psychiatric and neurological diseases. For the moment, this overview article, in particular the summary tables, should serve as our contact point in these affairs. 16 The NAC amount used in these studies was typically in the range from 2.0 to 2.4 grams NAC per day, orally administered and divided into 2 cans.
For those of us who were already trained in naturopathy, when Nac was used exclusively as a mucolytic, this new application spectrum is quite fascinating.
This current paper from Rapado-Castro now suggests that NAC could be of even greater use after long-term psychiatric weakness. This is even more fascinating, since NAC can offer advantages under conditions that we used to do that they were too old and too deeply rooted in order to be improved.
- Berk M., Copolov D., Dean O., et al. N-acetylcysteine as a glutathione predecessor for schizophrenia-a double-blind, randomized, placebo-controlled study. biopsychiatry . 2008; 64 (5): 361-368.
- National Institute for Mental Health. schizophrenia . (Link away). Accessed on May 2, 2016.
- National Institute for Mental Health. Schizophrenia. (Link away). Accessed on May 2, 2016.
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- Yarema Mc, Johnson DW, Berlin RJ, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute paracetamol poisoning. ann emererg.med . 2009; 54 (4): 606-614.
- Sadowska on. N-Acetylcystein mucolysis in the treatment of chronic obstructive lung disease. Ther Adv Respir Dis . 2012; 6 (3): 127-135.
- Daulletbaev, N., Fischer, P., Aulbach, B., et al. A phase II study on the safety and effectiveness of high-dose N-acetylcysteine in patients with cystic fibrosis. EUR J med res . 2009; 14 (8): 352-358.
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- Liu XH, XU cy, fan gh. Effectiveness of n-acetylcysteine in the prevention of atrial fibrillation after heart surgery: a meta-analysis of published randomized controlled studies. BMC Cardiovasc Disord . 2014; 14: 52.
- Geiler J., Michaelis M., Naczk P. et al. N-Acetyl-L-cysteine (NAC) inhibits viral replication and expression of inflammatory molecules in A549 cells that are infected with the highly pathogenic H5N1-Influenza virus. biochem Pharmacol . 2010; 79 (3): 413-420.
- Samuni Y, Goldstein S, Dean Om, Berk M. The chemistry and biological activities of N-Acetylcystein. Biochim Biophys Acta . 2013; 1830 (8): 4117-4129.
- Moussawi K, Pacchioni A, Moran M, Olive Mf, Gass Jt, Lavin A, Kalivas PW. N-acetylcysteine reverses the metaplasticity induced by cocaine. nat Neurosci . 2009; 12 (2): 182-189.
- Lee BR, Dong Y. Kokain-induced metaplasticity in the Nucleus Accumbens: Silent Synapse and beyond. neuropharmacology . 2011; 61 (7): 1060-1069.
- Berk M, Malhi GS, Gray LJ, Dean Om. The promise of n-acetylcysteine in neuropsychiatry. Trends pharmacol sci . 2013; 34 (3): 167-177.
- Hoffer Me, Balaban C, Slade MD, TSAO JW, Hoffer B. Improvement of the acute consequences of a blast-induced light traumatic brain injury by N-Acetylcystein: a double-blind, placebo-controlled study. plus one . 2013; 8 (1): E54163.
- Deepmala, Slattery J., Kumar N., et al. Clinical studies on N-Acetylcystein in psychiatry and neurology: a systematic review. neurosci biobehav rev . 2015; 55: 294-321.