Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. (August 2015)

• Record Type: Journal Article
• Authors: Deepmala, ; Slattery, John; Kumar, Nihit; Delhey, Leanna; Berk, Michael; Dean, Olivia; Spielholz, Charles; Frye, Richard
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 55(2015:Aug.)
• Page Start: 294
• Page End: 321
• Publication Date: 2015-08
• Subjects: ABC Aberrant Behavior Checklist -- AD Alzheimer's disease -- ADCS-ADL Alzheimer's Disease Cooperative Study – Activities of Daily Living -- ADHD attention deficit hyperactivity disorder -- ADL Activities of Daily Living -- ADP adenosine diphosphate -- AE adverse effects -- AIMS Abnormal Involuntary Movement Scale -- ALL acute lymphoblastic leukemia -- ALS amyotrophic lateral sclerosis -- AN animal naming test -- ASD autism spectrum disorder -- ASRS ADHD Self Report Scale -- ATP adenosine triphosphate -- BAS Barnes Akathisia Scale -- BDRS Bipolar Depression Rating Scale -- BE benzoylecgonine -- BID twice daily -- BP blood pressure -- BPAD bipolar disorder -- BSCS Brief Substance Craving Scale -- CCQ-Brief Cocaine Craving Questionnaire-Brief -- CGI Clinical Global Impression -- CGI-I Clinical Global Impression – Improvement -- CGI-S Clinical Global Impression – Severity -- CLOX-1 Clock Drawing Executive Test -- CO carbon monoxide -- COWA Controlled Oral Word Association Test -- CSSA Cocaine Selective Severity Assessment -- DA dopamine -- DBPC Double Blind Placebo Control Trial -- DE detrimental -- Dep depressive disorder -- DNA deoxyribonucleic acid -- DRS-2 Dementia Rating Scale-2 -- DTE dithioerythritol -- DTT dithiothreitol -- ESRS Extrapyramidal Symptom Rating Scale -- F female -- FDA Food and Drug Administration -- FTQ Fagerström Tolerance Questionnaire -- g/d grams per day -- G grams -- GAF Global Assessment of Functioning -- GI gastrointestinal -- GOR grade of recommendation -- G-SAS Gambling Symptom Assessment Scale -- GSH glutathione -- GSSG glutathione disulphide -- GTCS Generalized Tonic Clonic Seizures -- HA headache -- HARS Hamilton Anxiety Rating Scale -- HDRS Hamilton Depression Rating Scale -- HIV human immunodeficiency virus -- 5-HT serotonin -- ICAM intercellular adhesion molecule -- IFN interferon -- IL interleukin -- IU international units -- LIFE-RIFT Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool -- LOE level of evidence -- LPS lipopolysacchride -- LTD long term depression -- LTP long term potentiation -- M male -- MADRS Montgomery–Asberg Depression Scale -- MAOI monoamine oxidase inhibitor -- MAP methamphetamine -- MCQ Marijuana Craving Questionnaire -- MDD major depressive disorder -- μg micrograms -- mg milligrams -- MGH-HPS Massachusetts General Hospital Hair Pulling Scale -- MMSE Mini-Mental Status Examination -- MNWS Minnesota Nicotine Withdrawal Scale -- mRNA messenger ribonucleic acid -- NA nucleus accumbens -- NAC N-acetylcysteine -- NACA N-acetylcysteine amide -- NAM N-acetylmethionine -- NE neutral effect -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- NIMH-TSS National Institute of Mental Health Trichotillomania Severity Scale -- NMDA N-methyl d-aspartate -- NPI Neuropsychiatric Inventory -- NR not reported -- OCD obsessive compulsive disorder -- OR odds ratio -- PANSS Positive and Negative Syndrome Scale -- PB placebo -- PFC pre-frontal cortex -- PG pathological gambling -- PG-YBOCS Pathological Gambling-Yale-Brown Obsessive Compulsive Scale -- PICO Problem-Intervention-Comparison-Outcomes Framework -- PITS Psychiatric Institute Trichotillomania Scale -- Q-LES-Q Quality of Life Enjoyment and Satisfaction Questionnaire -- QSU Questionnaire of Smoking Urges -- RBS-R Repetitive Behavior Scale-Revised -- RCT randomized controlled trial -- ROS reactive oxygen species -- SAS Simpson–Angus Scale -- SC single case report or series -- SD standard deviation -- SDS Sheehan Disability Scale -- SLE systemic lupus erythematosus -- SLICE-LIFE Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation -- SMD spinal muscular dystrophy -- SN sensorineural -- SOFAS Social and Occupational Functioning Assessment Scale -- SQ subcutaneous -- SR systematic review -- SRS Social Responsiveness Scale -- SSRI selective serotonin reuptake inhibitor -- SU substance use -- TBI traumatic brain injury -- TID three times daily -- TMT Timed Trail Making Test A and B -- TNF tumor necrosis factor -- TSC Trichotillomania Scale for Children -- TTM trichotillomania -- UDS urine drug screen -- ULD Unverricht–Lundborg Disease -- VAS Visual Analog Scale -- Vit vitamin -- Wk weeks -- Y-BOCS Yale Brown Obsessive Compulsive Scale -- YMRS Young Mania Rating Scale; N-acetylcysteine (NAC) -- Psychiatry -- Neurology -- Mechanism of action; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2015.04.015
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: NAC is a promising treatment for several psychiatric and neurological disorders. Further larger controlled clinical trials are needed. 2.0–2.4 g oral NAC total daily dosing was safe and well tolerated. Abstract: N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable.