Summary of clinical findings of N-acetylcysteine (NAC) treatment in psychiatric illness
| Study | Disorder | No. study participants | Total daily dose, mg | Study design | Outcome measures | Findings |
|---|---|---|---|---|---|---|
| Gray et al. (31) | Marijuana addiction | 24 | 2400 | 4-wk open-label trial | Marijuana Craving Questionnaire | Improvement in 3 of the 4 domains of the scale |
| Knackstedt et al. (32) | Reduction in nicotine use | 29 | 2400 | 4-wk double-blind placebo-controlled trial | Questionnaire for Smoking Urges- Brief, Minnesota Nicotine Withdrawal Scale | Trend for improvement after covarying for alcohol use but overall a negative trial |
| Van Schooten et al. (33) | Chemo-prevention trial in healthy smokers (unable to quit) | 41 | 1200 | 6-mo double-blind placebo-controlled trial | Cotinine (plasma and BAL fluid), urine mutagenicity, 4-ABP-Hb adducts, lipophilic-DNA adducts (PBL and BAL cells), 8-OH-dG adducts (BAL cells), PAH-DNA adducts (MFC and BMC), micronuclei (MFC and SPC), TEAC (plasma and BAL fluid) | Decreases in lipophilic DNA adducts, 8-OH-dG levels and number of micronuclei |
| LaRowe et al. (34) | Cocaine addiction | 13 | 2400 | Crossover design, treatment for 2 d in each arm (NAC and placebo) | CSSA, self-reported cocaine use, reported cravings, routine blood tests | Significant decrease in craving, withdrawal and self-reported use in NAC but not placebo group (no between- group differences) |
| LaRowe et al. (35) | Cocaine addiction | 15 | 2400 | Crossover design, treatment for 2 d in each arm (NAC and placebo) | Cue-reactivity (general and motivational measures) | Decreased desire and interest in cocaine and reduced time spent looking at cocaine-related slides |
| Mardikian et al. (36) | Cocaine addiction | 23 | 1200, 2400 and 3600 | 4-wk, open-label trial | Days and amount of money spent on cocaine, CSSA and urine drug screen | Nonsignificant trends in reductions of amount spent and number of days of use on cocaine and improvements based on CSSA |
| Grant et al. (37) | Pathological gambling | 29 O/L 16 random | 1800† | 8-wk O/L study followed by a 6-wk double-blind, placebo- controlled trial (in responders only) | Y-BOCS adapted for Pathological Gambling (PGYBOCS), G-SAS, CGI Improvement and Severity scales, Sheehan Disability Scale, HAM-D, HAM-A, Quality of Life Inventory | Decreased PG-YBOCS scores during O/L phase. Sixteen of original 27 were classified as responders, 13 of whom continued to double-blind phase. There was an increased number of continued response in the NAC group and trends toward significance in the PG-YBOCS and G-SAS scales. |
| Lafleur et al. (38) | OCD | 1 | 3000† | 13 wk | Y-BOCS and HAM-D | Improvements between baseline and end point on Y-BOCS and HAM-D |
| Odlaug et al. (39) | TTM | 2 | 1800 | 10 and 13 wk | Self-reported behaviour | Complete abstinence from hair pulling |
| Grant et al. (40) | TTM | 50 | 1200–2400 | 12-wk double-blind, placebo-controlled trial | MGH-HPS, CGI, PITS, Sheehan Disability Scale, Quality of Life Scale, HAM-A and HAM-D | Significant improvements in MGH-HPS, PITS, CGI severity scale scores in the NAC group compared with placebo |
| Odlaug et al. (39) | Nail biting | 1* | 1800† | 13 wk | Self-reported behaviour | Complete abstinence from nail biting after 9 weeks of treatment. A 2-week hiatus caused reinstatement of symptoms, but subsequent NAC treatment again ameliorated this. |
| Berk et al. (41) | Nail biting | 3 | 2000 | 6 mo | Self-reported behaviour | Complete abstinence of symptoms that continued after 1-month washout period |
| Odlaug et al. (39) | Skin picking | 1 | 1800† | 13 wk | Self-reported behaviour | Decreased urge and act of skin picking |
| Berk et al. (42) | Schizophrenia | 140 | 2000 | 6-mo double-blind placebo-controlled trial | PANSS, CGI, GAF, SOFAS, BAS, Simpson–Angus Scale and the Abnormal Involuntary Movements Scale | Improvements seen in negative symptoms based on PANSS; improvements also seen on CGI and BAS. Improvements were lost at the 1-month follow-up visit. |
| Lavoie et al. (12) | Schizophrenia | 11 | 2000 | 8-wk double-blind crossover design | Mismatched negativity and plasma glutathione concentration | Significant improvements in mismatch negativity in NAC group. Plasma glutathione levels were increased following NAC treatment. |
| Bulut et al. (43) | Schizophrenia | 1 | 600 | 30 d | PANSS, CGI and Calgary depression scale | Reduction in PANSS and CGI scores |
| Berk et al. (44) | Bipolar disorder | 76 | 2000 | 6-mo double-blind placebo-controlled trial | MADRS, Bipolar Depression Rating Scale, Young Mania Rating Scale, CGI-bipolar version, GAF, SOFAS, SLICE/LIFE, LIFE-RIFT, and the Quality of Life Enjoyment and Satisfaction Questionnaire | Positive results showed improvements on most rating scales (including primary outcome measure MADRS) in NAC group compared with placebo group |
BAL = bronchoalveolar lavage; BAS = Barnes Akathisia Scale; BMC = buccal mucosa cell; CGI = Clinical Global Impression; CSSA = Cocaine Selective Severity Assessment; GAF = Global Assessment of Functioning; G-SAS = Gambling Symptom Assessment Scale; HAM-A = Hamilton Rating Scale for Anxiety; HAM-D = Hamilton Rating Scale for Depression; LIFE-RIFT = Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool; MADRS = Montgomery–Åsberg Depression Rating Scale; MFC = mouth floor cell; MGH-HPS = Massachusetts General Hospital Hair Pulling Scale; OCD = obsessive–compulsive disorder; O/L = open label; PAH = polycyclic aromatic hydrocarbon; PANSS = Positive and Negative Symptoms Scale; PBL = peripheral blood lymphocyte; PITS = Psychiatric Institute Trichotillomania Scale; random. = randomized; SLICE/LIFE = Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation; SOFAS = Social and Occupational Functioning Scale; SPC = soft palate cell; TEAC = trolox equivalent antioxidant capacity; TTM = trichotillomania; Y-BOCS = Yale–Brown Obsessive Compulsive Scale.
↵* This participant also had TTM.
↵† Titrated dose.