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N-Acetylcysteine, a Glutamate Modulator, in the Treatment of Trichotillomania: A Double-blind, Placebo-Controlled Study
Abstract
Context Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss. Data on the pharmacologic treatment of trichotillomania are limited to conflicting studies of serotonergic medications. N-acetylcysteine, an amino acid, seems to restore the extracellular glutamate concentration in the nucleus accumbens and, therefore, offers promise in the reduction of compulsive behavior. Objective To determine the efficacy and tolerability of N-acetylcysteine in adults with trichotillomania. Design Twelve-week, double-blind, placebo-controlled trial. Setting Ambulatory care center. Patients Fifty individuals with trichotillomania (45 women and 5 men; mean [SD] age, 34.3 [12.1] years). Interventions N-acetylcysteine (dosing range, 1200-2400 mg/d) or placebo was administered for 12 weeks. Main outcome measures Patients were assessed using the Massachusetts General Hospital Hair Pulling Scale, the Clinical Global Impression scale, the Psychiatric Institute Trichotillomania Scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using analysis of variance modeling analyses and linear regression in an intention-to-treat population. Results Patients assigned to receive N-acetylcysteine had significantly greater reductions in hair-pulling symptoms as measured using the Massachusetts General Hospital Hair Pulling Scale (P Conclusions This study, the first to our knowledge that examines the efficacy of a glutamatergic agent…
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“The glutamate modulator n‐acetyl cysteine has shown evidence of efficacy, in double‐blind placebo‐controlled studies, for OC‐related disorders trichotillomania and skin‐picking disorder”
From Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction (2023) · cites this paper as Grant et al., 2009
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“4% reduction in the MGHHPS score).(49,50,57) These findings suggest that Nacetylcysteine compares favorably with existing treatment options available to physicians.”
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The chemistry and biological activities of N-acetylcysteine
Samuni, Y., Goldstein, S., Dean, O. M., & Berk, M. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.04.016 · Cited by 876
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“In fact, both GSH (Agarwal & Shukla, 1999) and glutamate levels (Grant et al. 2009) can be elevated with pharmacological treatment by N-acetylcysteine (NAC).”
N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action
Dean, O., Giorlando, F., & Berk, M. (2011) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.100057 · Cited by 494
“Grant et al.(40) TTM 50 1200–2400 12-wk double-blind, placebo-controlled trial MGH-HPS, CGI, PITS, Sheehan”
MethodInfluentialFineberg, N. A., Chamberlain, S. R., Goudriaan, A. E., Stein, D. J., Vanderschuren, L. J. M. J., Gillan, C. M., Shekar, S., Gorwood, P. A. P. M., Voon, V., Morein-Zamir, S., et al. (2014) · CNS Spectrums · doi:10.1017/s1092852913000801 · Cited by 488
“However, unlike OCD, trichotillomania appears SSRI-unresponsive, and data from single randomized controlled trials suggest that monotherapy with olanzapine (an antipsychotic agent)(15) and n-acetyl cysteine (an amino acid compound) can be effective.(16) Antipsychotics represent first-line treatment for Tourette syndro…”
BackgroundClinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review
Deepmala, Slattery, J., Kumar, N., Delhey, L., Berk, M., Dean, O., Spielholz, C., & Frye, R. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.015 · Cited by 463
The promise of N-acetylcysteine in neuropsychiatry
Berk, M., Malhi, G. S., Gray, L. J., & Dean, O. M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.01.001 · Cited by 434
Pittenger, C., Bloch, M. H., & Williams, K. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.09.006 · Cited by 426
“Subsequently , however, a well-controlled trial showed striking benefit in adult patients with trichotillomania (Grant et al., 2009).”
BackgroundOxidative stress in anxiety and comorbid disorders
Hovatta, I., Juhila, J., & Donner, J. (2010) · Neuroscience Research · doi:10.1016/j.neures.2010.08.007 · Cited by 365
Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V?
Phillips, K. A., Stein, D. J., Rauch, S. L., Hollander, E., Fallon, B. A., BARSKY, A. J., Fineberg, N. A., Mataix‐Cols, D., Ferrão, Y. A., Saxena, S., et al. (2010) · Depression and Anxiety · doi:10.1002/da.20705 · Cited by 355
“low-dose atypical neuroleptics as monotherapy or n-acetylcysteine, although data are not definitive.([260,261]) TTM may also respond to some interventions used for other ICDs (e.”
MethodA randomized controlled pilot trial of oral N-acetylcysteine in children with autism
Hardan, A. Y., Fung, L. K., Libove, R. A., Obukhanych, T. V., Nair, S., Herzenberg, L. A., Frazier, T. W., & Tirouvanziam, R. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.014 · Cited by 293
“In a 12-week, double-blind, placebo-controlled investigation, NAC was found to be effective in decreasing hair-pulling symptoms in adults with trichotillomania (21).”
BackgroundImpulse Control Disorders: Updated Review of Clinical Characteristics and Pharmacological Management
Schreiber, L. R. N., Odlaug, B., & Grant, J. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00001 · Cited by 271
Self-citationSmaga, I., Niedzielska, E., Gawlik, M., Moniczewski, A., Krzek, J., Przegaliński, E., Pera, J., & Filip, M. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2014.12.015 · Cited by 252
“[70] Strawn JR, Saldana SN. Treatment with adjunctive N-acetylcysteine in an adolescent with selective serotonin reuptake inhibitor-resistant anxiety.”
BackgroundInfluentialUhl, G. R., Koob, G. F., & Cable, J. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13989 · Cited by 286
Grant, J. E., & Chamberlain, S. R. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.15111432 · Cited by 252
Self-citationN-acetylcysteine Boosts Brain and Blood Glutathione in Gaucher and Parkinson Diseases
Holmay, M. J., Terpstra, M., Coles, L. D., Mishra, U., Ahlskog, M., Öz, G., Cloyd, J. C., & Tuite, P. J. (2013) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e31829ae713 · Cited by 216
“There are reports of positive effects of oral NAC in disorders with central nervous system involvement.(29,30) Future studies are necessary to determine if oral NAC affects brain [GSH] and if so, to establish optimal dosage regimens to attain sustained elevation of brain [GSH] with repeated dosing.”
BackgroundGlutamatergic medications for the treatment of drug and behavioral addictions
Olive, M. F., Cleva, R. M., Kalivas, P. W., & Malcolm, R. J. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.04.015 · Cited by 211
“Finally, NAC was also shown to suppress hair-pulling in a double-blind study of 50 patients with trichotillomania (Grant et al., 2009).”
BackgroundStein, D. J., Grant, J., Franklin, M., Keuthen, N., Lochner, C., Singer, H., & Woods, D. W. (2010) · Depression and Anxiety · doi:10.1002/da.20700 · Cited by 208
“Similarly, there may be specific pharmacotherapy interventions for TTM, such as N-acetylcysteine, which have not been widely studied in the impulse control disorders.([44]) Trichotillomania as an OCD spectrum disorder.”
BackgroundSelf-citationBridges, R., Lutgen, V., Lobner, D., & Baker, D. A. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003889 · Cited by 205
“In addition, N-acetylcysteine has been shown to reduce pathological gambling and lessen other types of compulsive behaviors, such as trichotillomania (Grant et al., 2007, 2009; Knackstedt et al., 2009).”
BackgroundResultTrichotillomania: A current review
Duke, D. C., Keeley, M. L., Geffken, G. R., & Storch, E. A. (2009) · Clinical Psychology Review · doi:10.1016/j.cpr.2009.10.008 · Cited by 214
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Fineberg, N. A., Apergis-Schoute, A. M., Vaghi, M. M. S., Banca, P., Gillan, C. M., Voon, V., Chamberlain, S. R., Cinosi, E., Reid, J. E., Shahper, S., et al. (2017) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx088 · Cited by 195
“Other data from single randomized controlled trials in hair-pulling disorder suggest that olanzapine (an antipsychotic agent) (Van Ameringen et al., 2010) and n-acetyl cysteine (an amino acid compound) (Grant et al., 2009) could be effective.”
BackgroundUsing glutamate homeostasis as a target for treating addictive disorders
Reissner, K. J., & Kalivas, P. W. (2010) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32833d41b2 · Cited by 201
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Amen, S. L., Piacentine, L., Ahmad, M. E., Li, S.-J., Mantsch, J. R., Risinger, R., & Baker, D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.226 · Cited by 179
“In addition to cocaine, N-acetyl cysteine has been shown to decrease tobacco use by smokers, reduce pathological gambling, and lessen other types of compulsive behaviors such as trichotillomania (Grant et al. , 2007; Grant et al. , 2009; Knackstedt et al. , 2009).”
Snorrason, I., Belleau, E. L., & Woods, D. W. (2012) · Clinical Psychology Review · doi:10.1016/j.cpr.2012.05.008 · Cited by 174
N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)
Schwalfenberg, G. (2021) · Journal of Nutrition and Metabolism · doi:10.1155/2021/9949453 · Cited by 198
“An RCT trial using NAC for treatment of trichotillomania showed significant benefit [137].”
MethodN-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial
Grant, J. E., Chamberlain, S. R., Redden, S. A., Leppink, E. W., Odlaug, B. L., & Kim, S. W. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.0060 · Cited by 172
Self-citationBloch, M., Panza, K. E., Grant, J., Pittenger, C., & Leckman, J. (2013) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1016/j.jaac.2012.12.020 · Cited by 171
Self-citationImpulsive and Compulsive Behaviors in Parkinson's Disease
Averbeck, B. B., O’Sullivan, S. S., & Djamshidian, A. (2013) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032813-153705 · Cited by 73
A Double-Blind Placebo-Controlled Trial of N-Acetylcysteine in the Treatment of Cocaine Dependence
Larowe, S., Kalivas, P., Nicholas, J. S., Randall, P., Mardikian, P., & Malcolm, R. (2013) · American Journal on Addictions · doi:10.1111/j.1521-0391.2013.12034.x · Cited by 154
Ting, J. T., & Feng, G. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.04.010 · Cited by 143
“It is of great interest that NAC is currently being explored in clinical trials for the treatment of OCD on the basis of putative antiglutamatergic properties relating to transporter activity [4], and recent studies indicate an improvement in symptom severity with NAC treatment in SSRI-refractory OCD and TTM patients…”
BackgroundMcGuire, J. F., Ung, D., Selles, R. R., Rahman, O., Lewin, A. B., Murphy, T. K., & Storch, E. A. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.07.015 · Cited by 142
“While demonstrating efficacy in a RCT of adults with TTM (Grant et al., 2009), no significant benefit was found relative to placebo in a sample of youth with TTM (Bloch et al., 2013).”
BackgroundGlutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders
Roberts-Wolfe, D., & Kalivas, P. W. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527314666150529144655 · Cited by 149
“Other disorders of compulsive behavior In addition to the effects on substance abuse listed above, NAC has demonstrated efficacy for treatment of pathological gambling (70, 85), and demonstrated a large effect size for treatment of trichotillomania (86).”
BackgroundAfshar, H., Roohafza, H., Mohammad-Beigi, H., Haghighi, M., Jahangard, L., Shokouh, P., Sadeghi, M., & Hafezian, H. (2012) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318272677d · Cited by 136
“These findings are consistent with the reports of previous trials of NAC with the same dose and route of administration, which showed the agent to be safe and well tolerated.(30,45) Although this study has the advantage of being randomized and placebo controlled, we would like to note that generalizability of the conc…”
ResultFarhat, L. C., Olfson, E., Nasir, M., Levine, J. L. S., Li, F., Miguel, E. C., & Bloch, M. H. (2020) · Depression and Anxiety · doi:10.1002/da.23028 · Cited by 133
DSM-5 OBSESSIVE-COMPULSIVE AND RELATED DISORDERS: CLINICAL IMPLICATIONS OF NEW CRITERIA
Ameringen, M. V., Patterson, B. A., & Simpson, W. S. (2014) · Depression and Anxiety · doi:10.1002/da.22259 · Cited by 141
“More recent studies have shown some benefit with the use of antipsychotic agents in TTM as well as glutamatergic agents such as N-acetylcysteine.[51] Similarly, there is also evidence that the opiod antagonist, naltrexone, may be effective in treating TTM[52] and skin picking,[49] although not effective in the treatme…”
Trichotillomania and its treatment: a review and recommendations
Franklin, M., Zagrabbe, K., & Benavides, K. L. (2011) · Expert Review of Neurotherapeutics · doi:10.1586/ern.11.93 · Cited by 130
N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects
Minarini, A., Ferrari, S., Galletti, M., Giambalvo, N., Perrone, D., Rioli, G., & Galeazzi, G. M. (2016) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1251580 · Cited by 126
“[62] Trichotillomania 1200–2400 mg 50 Double-blind placebo controlled trial Improved MGH-HPS, PITS, and CGI”
MethodExcoriation (skin-picking) disorder: a systematic review of treatment options
Lochner, C., Roos, A., & Stein, D. J. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s121138 · Cited by 122
“2,34,35 Glutamate is a key excitatory central nervous system (CNS) neurotransmitter, and the glutamatergic system has been targeted for pharmacologic manipulation in OCRDs.”
Quality of life and clinical severity in pathological skin picking and trichotillomania
Odlaug, B. L., Kim, S. W., & Grant, J. E. (2010) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2010.06.004 · Cited by 118
Self-citationObsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction
Jalal, B., Chamberlain, S. R., & Sahakian, B. J. (2023) · Brain and Behavior · doi:10.1002/brb3.3000 · Cited by 111
“The glutamatemodulator n-acetyl cysteine has shown evidence of efficacy, in double-blind placebo-controlled studies, for OC-related disorders trichotillomania and skin-picking disorder, which are OCrelated disorders (Grant et al., 2009; Grant et al., 2016).”
BackgroundBehavioural addiction-A rising tide?
Chamberlain, S., Lochner, C., Stein, D., Goudriaan, A., van Holst, R. V., Zohar, J., & Grant, J. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.08.013 · Cited by 108
“Opioid antagonists (e.g., naltrexone, nalmefene), well researched for the treatment of alcohol and opiate use disorders, have shown efficacy in controlled clinical trials (three positive) for gambling disorder and (one positive trial) for kleptomania (Grant et al. 2009a; van den Brink 2012).”
Self-citationPharmacotherapy for trichotillomania
Rothbart, R., Amos, T., Siegfried, N., Ipser, J. C., Fineberg, N., Chamberlain, S. R., & Stein, D. J. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007662.pub2 · Cited by 106
Comorbidity and quality of life in adults with hair pulling disorder
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Diagnosis, Evaluation, and Management of Trichotillomania
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“The Fernandes study (35) also included tobacco use disorder (59) and trichotillomania (60), hence explored a heterogeneous sample.”
BackgroundOdlaug, B. L., & Grant, J. E. (2010) · The American Journal of Drug and Alcohol Abuse · doi:10.3109/00952991003747543 · Cited by 97
“NAC has demonstrated benefit for both trichotillomania and cocaine addiction (53, 54).”
BackgroundSelf-citationA Double-Blind, Placebo-Controlled Trial of Lamotrigine for Pathological Skin Picking
Grant, J. E., Odlaug, B. L., Chamberlain, S. R., & Kim, S. W. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181e617a1 · Cited by 89
Self-citationThe Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders
Bradlow, R. C. J., Berk, M., Kalivas, P. W., Back, S. E., & Kanaan, R. A. (2022) · CNS Drugs · doi:10.1007/s40263-022-00907-3 · Cited by 87
Duailibi, M. S., Cordeiro, Q., Brietzke, E. M., Ribeiro, M., LaRowe, S. D., Berk, M., & Trevizol, A. P. (2017) · American Journal on Addictions · doi:10.1111/ajad.12620 · Cited by 87
Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines
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Behavior Therapy for Pediatric Trichotillomania: A Randomized Controlled Trial
Franklin, M., Edson, A. L., Ledley, D. A., & Cahill, S. (2011) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1016/j.jaac.2011.05.009 · Cited by 84
Pilot trial of dialectical behavior therapy-enhanced habit reversal for trichotillomania
Keuthen, N. J., Rothbaum, B. O., Welch, S. S., Taylor, C., Falkenstein, M., Heekin, M., Jordan, C. A., Timpano, K., Meunier, S., Fama, J., et al. (2010) · Depression and Anxiety · doi:10.1002/da.20732 · Cited by 81
“More recently, Grant et al.([10]) reported successful outcomes using N-acetylcysteine, an amino acid known to modulate glutamate function, in a doubleblind, placebo-controlled study of TTM.”
Selles, R. R., McGuire, J. F., Small, B. J., & Storch, E. A. (2016) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2016.04.001 · Cited by 80
Obsessive compulsive disorder and the glutamatergic system
Kariuki, C. M., Gomez‐Mancilla, B., & Stein, D. J. (2013) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000017 · Cited by 82
“Notably, however, NAC was effective in a RCT of trichotillomania in adults [70] with some case reports of efficacy in skin picking [71].”
BackgroundSarris, J. J., Oliver, G., Camfield, D., Dean, O. M., Dowling, N. L., Smith, D. J., Murphy, J., Menon, R., Berk, M., Blair‐West, S., et al. (2015) · CNS Drugs · doi:10.1007/s40263-015-0272-9 · Cited by 85
“4g/day) significantly reduced symptoms on the Massachusetts General Hospital Hair Pulling Scale, and the Psychiatric Institute Trichotillomania Scale [24].”
BackgroundNasir, M., Trujillo, D., Levine, J. L. S., Dwyer, J. B., Rupp, Z. W., & Bloch, M. H. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.548505 · Cited by 94
“However, when anxiety symptoms were analyzed in placebo-controlled trials looking at major depressive disorder (154) and trichotillomania (155), no significant differences were found in anxiety scores as measured by Hamilton Anxiety Rating Scale (HAM-A).”
MethodKranzer, K., Elamin, W., Cox, H., Seddon, J., Ford, N., & Drobniewski, F. (2015) · Thorax · doi:10.1136/thoraxjnl-2015-207245 · Cited by 72
“Grant, 2009 b [11] USA Trichotillomania 1200 (6wks), 2400 (6wks) 1 12 25 25 32.”
BackgroundInfluentialN‐acetylcysteine as a new prominent approach for treating psychiatric disorders
Smaga, I., Frankowska, M., & Filip, M. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15456 · Cited by 73
“4.8.2 | Controlled In 2009, the first double-blind, placebo-controlled trial examining NAC in patients with TTM was published (Grant et al., 2009).”
BackgroundMethodInfluentialRichert, B., & André, J. (2011) · American Journal of Clinical Dermatology · doi:10.2165/11537110-000000000-00000 · Cited by 71
“The dosage in adults ranges between 1200 and 2400mg/day.([119]) For severe cases, antidepressants (e.”
An open‐label pilot study of N‐acetylcysteine for skin‐picking in Prader–Willi syndrome
Miller, J. L., & Angulo, M. (2014) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.36306 · Cited by 70
“…valproic Ac; GH, growth hormone; MEF, metformin; QPE, quetiapine; RSP, risperdone; SPR, spiro aLesions present for over 90 days prior to treatment. bPatient had in addition trichotillomania, which resolved with treatment. and nail biting [Grant et al., 2009; Rodrigues-Barata et al., 2012].”
BackgroundMechanisms of divalent metal toxicity in affective disorders
Menon, A. V., Chang, J., & Kim, J. (2015) · Toxicology · doi:10.1016/j.tox.2015.11.001 · Cited by 77
Lara, D. R., Bisol, L. W., Brunstein, M. G., Reppold, C. T., de Carvalho, H. W., & Ottoni, G. L. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.08.036 · Cited by 80
“…as diverse as schizophrenia (mostly negative and general symptoms) (Berk et al., 2008a), cocaine addiction (LaRowe et al., 2007), bipolar depression (Berk et al., 2008b), pathological gambling (Grant et al., 2007), trichotillomania (Grant et al., 2009) and possibly nail biting (Berk et al., 2009).”
BackgroundEffect of N‐acetylcysteine on motivation, seeking and relapse to ethanol self‐administration
Lebourgeois, S., González‐Marín, M. C., Jeanblanc, J., Naassïla, M., & Vilpoux, C. (2017) · Addiction Biology · doi:10.1111/adb.12521 · Cited by 74
N-acetylcysteine in the Treatment of Trichotillomania
Rodrigues-Barata, A. R., Tosti, A., Rodriguez-Pichardo, A., & Camacho-Martínez, F. (2012) · International Journal of Trichology · doi:10.4103/0974-7753.100090 · Cited by 65
Neuromodulation for obsessive-compulsive disorder
Lapidus, K. A. B., Stern, E. R., Berlin, H. A., & Goodman, W. K. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0287-9 · Cited by 63
“Also, preliminary evidence suggests that glutamatergic agents such as riluzole and ketamine may be useful in OCD [28–31].”
A Practical Approach to the Diagnosis and Management of Hair Loss in Children and Adolescents
Xu, L.-W., Liu, K. X., & Senna, M. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00112 · Cited by 63
“While N-acetylcysteine is a promising agent that reduces symptoms in adults, no benefit was seen in children (64, 65).”
BackgroundOdlaug, B. L., Chamberlain, S. R., Derbyshire, K. L., Leppink, E. W., & Grant, J. E. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.08.010 · Cited by 69
Self-citationGhanizadeh, A. J., Derakhshan, N., & Berk, M. (2013) · Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry · doi:10.2174/1871523011312030003 · Cited by 64
Obsessive-Compulsive and Related Disorders
Leigh, H. (2014) · Springer eBooks · doi:10.1007/978-3-319-11005-9_24 · Cited by 32
Dronabinol, a cannabinoid agonist, reduces hair pulling in trichotillomania: a pilot study
Grant, J. E., Odlaug, B. L., Chamberlain, S. R., & Kim, S. W. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2347-8 · Cited by 63
“…R. Chamberlain Department of Psychiatry, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK demonstrated that N-acetyl cysteine (Grant et al. 2009), olanzapine (Van Ameringen et al. 2010), and clomipramine (Swedo et al. 1993) all show some promise in reducing hair-pulling…”
BackgroundResultInfluentialSelf-citationSarris, J., Camfield, D., & Berk, M. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.04.051 · Cited by 59
Emerging treatments in alopecia
Falto-Aizpurua, L. A., Choudhary, S., & Tosti, A. (2014) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2014.974550 · Cited by 66
“1 N-acetylcysteine Recently, N-acetylcysteine was investigated as a potential drug given that it increases glutamate extracellular concentration in the nucleus accumbens [66].”
BackgroundHistory of Psychosurgery: A Psychiatrist's Perspective
Lapidus, K. A. B., Kopell, B. H., Ben‐Haim, S., Rezai, A. R., & Goodman, W. K. (2013) · World Neurosurgery · doi:10.1016/j.wneu.2013.02.053 · Cited by 87
Camfield, D., Sarris, J. J., & Berk, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.02.011 · Cited by 62
“In a double-blind randomized placebo-controlled study Greenberg et al. (2009) administered 60 g/day of glycine to 24 adult OCD outpatients as augmentation therapy.”
MethodN-acetylcysteine in dermatology
Adil, M., Amin, S. S., & Mohtashim, M. (2018) · Indian Journal of Dermatology Venereology and Leprology · doi:10.4103/ijdvl.ijdvl_33_18 · Cited by 65
Jones, G., Keuthen, N., & Greenberg, E. H. (2018) · Clinical Dermatology · doi:10.1016/j.clindermatol.2018.08.008 · Cited by 54
Emamzadehfard, S., Kamaloo, A., Paydary, K., Ahmadipour, A., Zeinoddini, A., Ghaleiha, A., Mohammadinejad, P., Zeinoddini, A., & Akhondzadeh, S. (2016) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12394 · Cited by 56
“Another 12-week open-label trial of riluzole on six treatment-resistant children with OCD showed that four had >46% reduction in the Children’s Yale– Brown Obsessive–Compulsive Scale severity scores.(48) The authors noted that the side-effect profile was benign and that all patients elected to remain on riluzole post-…”
BackgroundTherapeutic potential of glutathione-enhancers in stress-related psychopathologies
Zalachoras, I., Hollis, F., Ramos‐Fernández, E., Trovò, L., Sonnay, S., Geiser, E., Preitner, N., Steiner, P., Sandi, C., & Morató, L. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.015 · Cited by 69
Möller, M., du Preez, J. L., Viljoen, F. P., Berk, M., & Harvey, B. H. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-013-9433-z · Cited by 48
“In this regard N-acetyl cysteine (NAC), a glutathione precursor, antioxidant (Kerksick and Willoughby, 2005) and glutamate modulator (Grant et al., 2009), is a promising therapeutic agent (Dean et al.”
BackgroundFrança, K., Kumar, A., Castillo, D., Jafferany, M., Hyczy da Costa Neto, M., Damevska, K., Wollina, U., & Lotti, T. (2019) · Dermatologic Therapy · doi:10.1111/dth.12622 · Cited by 51
Disordered reward processing and functional connectivity in trichotillomania: A pilot study
White, M. P., Shirer, W. R., Molfino, M. J., Tenison, C., Damoiseaux, J. S., & Greicius, M. D. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.05.014 · Cited by 53
“This may be relevant to recent clinical inroads in the treatment of TTM using agents that modulate glutamate (Grant et al., 2009) and dopamine (Van Ameringen et al.”
BackgroundInfluentialFlessner, C. A., Knopik, V. S., & McGeary, J. E. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2012.03.039 · Cited by 59
“…treatment study of the dopamine blocker pimozide (Stein and Hollander, 1992) and a more recent randomized controlled trial of N-acetylcysteine (NAC) for HPD (Grant et al., 2009) provides some additional support for the potentially important role of dopamine in the pathophysiology of HPD.”
Sani, G., Gualtieri, I., Paolini, M., Bonanni, L., Spinazzola, E., Maggiora, M., Pinzone, V., Brugnoli, R., Angeletti, G., Girardi, P., et al. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190320164223 · Cited by 50
The effect of N-acetylcysteine on alcohol use during a cannabis cessation trial
Squeglia, L. M., Tomko, R. L., Baker, N. L., McClure, E. A., Book, G. A., & Gray, K. M. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2017.12.005 · Cited by 59
Lee, D. K., & Lipner, S. R. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116370 · Cited by 47
Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach
Grados, M. A., Specht, M. W., Sung, H.-M., & Fortune, D. (2013) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2013.845553 · Cited by 49
Habit reversal training in trichotillomania: guide for the clinician
Morris Sarah, H., Zickgraf, H. F., Dingfelder, H. E., & Franklin Martin, E. (2013) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2013.827477 · Cited by 62
Connor, C. J. (2017) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s111041 · Cited by 48
“NAC is an amino acid that acts as a glutamate modulator and may exert its effects by normalizing dysregulated extracellular glutamate concentrations in the nucleus accumbens: an area of the brain that plays a key role in motivation and reward.(126) The common dose of NAC for trichotillomania is 1,200 mg/day, with few…”
Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder
Grassi, G., Cecchelli, C., Vignozzi, L., & Pacini, S. (2021) · Journal of Experimental Pharmacology · doi:10.2147/jep.s255375 · Cited by 44
Pharmacological Augmentations of SRIs for Obsessive Compulsive Disorder
Leppink, E. W., & Grant, J. E. (2017) · Wiley eBooks · doi:10.1002/9781118890233.ch16 · Cited by 43
Self-citationTreatment options for alopecia: an update, looking to the future
Miteva, M., & Tosti, A. (2012) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2012.685160 · Cited by 43
“N-acetylcysteine, an amino acid, seems to restore the extracellular glutamate concentration in the brain, and therefore offers promise in the reduction of compulsive behavior [64].”
BackgroundObsessive-Compulsive Related Disorders
Breet, E., & Löchner, C. (2015) · Springer eBooks · doi:10.1007/978-3-319-13060-6_5 · Cited by 4
Asplund, M., Rück, C., Lenhard, F., Gunnarsson, T., Bellander, M., Delby, H., & Ivanov, V. Z. (2021) · Journal of Clinical Psychology · doi:10.1002/jclp.23147 · Cited by 42
Current Treatment Practices for Children and Adults With Trichotillomania: Consensus Among Experts
Flessner, C. A., Penzel, F., & Keuthen, N. J. (2010) · Cognitive and Behavioral Practice · doi:10.1016/j.cbpra.2009.10.006 · Cited by 42
Cortico-striatal oxidative status, dopamine turnover and relation with stereotypy in the deer mouse
Güldenpfennig, M., Wolmarans, D. W., du Preez, J. L., Stein, D. J., & Harvey, B. H. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.03.008 · Cited by 45
“A recent placebo-controlled trial has also described its use in trichotillomania [53].”
Background
Metadata
- Authors
- Grant, J. E., Odlaug, B. L., & Won Kim, S.
- Affiliations
- University of Minnesota (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-07-01
- Volume
- 66
- Issue
- 7
- Pages
- 756
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2038083244
- Cited by
- 424
- References
- 0
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 17 · 2023: 35 · 2022: 15 · 2021: 22 · 2020: 23 · 2019: 22 · 2018: 31 · 2017: 23 · 2016: 31 · 2015: 41 · 2014: 28 · 2013: 27 · 2012: 29
- FWCI
- 29.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Dermatology › Hair Growth and Disorders
- Social Sciences › Psychology › Clinical Psychology › Body Image and Dysmorphia Studies
- Keywords
- trichotillomania, N-acetylcysteine, glutamate modulation, glutamatergic agents, compulsive behavior, hair pulling, nucleus accumbens, pharmacotherapy, treatment efficacy, tolerability, depression, anxiety, psychosocial functioning
- MeSH terms
- Acetylcysteine, Adolescent, Adult, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Personality Inventory, Psychometrics, Trichotillomania, Excitatory Amino Acid Agents, Young Adult
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