Role of Glutamatergic Modulators in the Treatment of Obsessive Compulsive and Related Disorders

Year 2024, Volume: 16 Issue: 3, 383 - 400, 30.09.2024

Fatma Gül Helvacı Çelik , Çiçek Hocaoğlu

https://doi.org/10.18863/pgy.1279927

Abstract

Due to the shared phenomenology and research findings related to disorders like obsessive-compulsive disorder (OCD), trichotillomania (TTM), body dysmorphic disorder (BDD), skin picking disorder (SPD), hoarding disorder (HD), and OCD, these conditions are collectively classified as Obsessive-Compulsive and Related Disorders (OCRDs) in the DSM-5. Despite having distinct features from OCD in terms of course and treatment outcomes, they are categorized together. The etiology of OCRDs remains incompletely understood, and information on their treatment is limited. Traditional pharmacological approaches often fall short in addressing the needs of many OCRD patients, necessitating alternative strategies. Recent research has shed light on a potential imbalance in glutamate, a crucial excitatory neurotransmitter in the brain, among certain patients with OCRDs. Findings from these studies suggest that glutamate modulators may be beneficial for individuals who do not respond to standard pharmacotherapeutic interventions. While no glutamate modulator has conclusively proven effective for OCD, promising results have been noted for memantine and riluzole. The evidence surrounding N-acetylcysteine (NAC) also positions it as a reasonable consideration for some patients. Noteworthy research on D-cycloserine (DCS) and ketamine has indicated potential benefits, and investigations into the off-label use of these pharmacological agents, originally approved for other indications, have been particularly focused on refractory OCRDs. It is essential to highlight that these drugs operate through diverse and, in some cases, opposing mechanisms. However, it is crucial to acknowledge that the existing studies on the use of these drugs in OCRDs are still insufficient. A more in-depth exploration of glutamate imbalance in the etiology of OCRDs is needed to better understand the role of glutamate modulators in treatment.

Keywords

Obsessive compulsive and related disorders, glutamate, D-cycloserine, ketamine, N-acetylcysteine

Supporting Institution

NO

Project Number

NO

Thanks

NO

Obsesif Kompulsif ve İlişkili Bozuklukların Tedavisinde Glutamaterjik Modülatörlerin Rolü

Abstract

Obsesif kompulsif bozukluk (OKB) gibi bozuklukların fenomenoloji ve çalışma bulgularının benzer olması nedeniyle; trikotillomani (TTM), beden dismorfik bozukluğu (BDB), deri yolma bozukluğu (DYB) ve istifleme bozukluğu (İB) ile OKB, DSM-5'te Obsesif Kompulsif ve İlişkili Bozukluklar (OKİB) tanısal sınıflandırması altında yer almıştır. Bu psikiyatrik bozuklukların seyri ve tedavi sonuçları gibi OKB'den ayırt edici özellikleri olduğu için ayrı bir tanı olarak değerlendirilmiştir. OKİB'daki psikiyatrik bozuklukların etiyolojisi tam olarak aydınlatılamamıştır ve tedavilerine ilişkin bilgiler de sınırlıdır. Öte yandan, OKİB'lu birçok hastanın tedavisinde farmakolojik yaklaşımlar yetersiz kalmaktadır. Bu nedenle alternatif farmakolojik tedavi stratejilerine ihtiyaç vardır. Etiyoloji üzerine yapılan son araştırmalar, bazı hastalarda beynin en önemli eksitatör nörotransmitteri olan glutamattaki dengesizliğe dikkat çekmiştir. Bu çalışmaların sonuçları, standart farmakoterapötik yaklaşımlara yanıt vermeyen hastaların tedavisinde glutamat modülatörlerinin kullanımını desteklemektedir. Hiçbir glutamat modülatörünün OKB için etkili bir tedavi olduğu kanıtlanmamasına rağmen, memantin ve riluzol için umut verici olabileceği bildirilmiştir. N-asetil sistein (NAC) için kanıtlar da bu ilacı bazı hastalar için makul bir değerlendirme haline getirmektedir. D-sikloserin ve ketamin üzerine yapılan ilginç araştırmalarda da potansiyel bir faydadan söz edilmiştir. Diğer endikasyonlar için onaylanmış bu farmakolojik ajanların etiket dışı kullanımı, özellikle dirençli OKİB'da araştırılmıştır. Bu ilaçların hepsinin farklı ve bazı durumlarda zıt mekanizmalarla çalışması da dikkat çekicidir. Ancak bu ilaçların OKİB'da kullanımı ile ilgili çalışmaların halen yetersiz olduğu unutulmamalıdır. OKİB etiyolojisinde glutamat dengesizliğinin daha fazla araştırılması, glutamat modülatörlerinin tedavideki rolünü daha da aydınlatacaktır.

Keywords

Obsesif kompulsif ve ilişkili bozukluklar, glutamat, D-sikloserin, ketamin, N-asetilsistein

Project Number

NO

References

• Aan Het Rot M, Zarate CA, Charney DS, Mathew SJ (2012) Ketamine for depression: where do we go from here?. Biol Psychiatry, 72:537–547.
• Abramowitz JS, Jacoby RJ (2015) Obsessive-compulsive and related disorders: a critical review of the new diagnostic class. Annu Rev Clin Psychol, 11:165-186.
• Afshar H, Roohafza H, Mohammad-Beigi H, Haghighi M, Jahangard L, Shokouh P et al. (2012) N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol, 32:797–803.
• Afshar H, Akuchekian S, Mahaky B, Zarean E (2014) Topiramate augmentation in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. J Res Med Sci, 19:976–981.
• Alonso P, Gratacós M, Segalàs C, Escaramís G, Real E, Bayés M et al. (2012) Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder. J Psychiatry Neurosci, 37:273–281.
• Andersson E, Hedman E, Enander J, Radu Djurfeldt D, Ljótsson B, Cervenka S et al. (2015) D-Cycloserine vs placebo as adjunct to cognitive behavioral therapy for obsessive-compulsive disorder and interaction with antidepressants: A randomized clinical trial. JAMA Psychiatry, 72:659-667.
• Andrade C (2019) Augmentation with memantine in obsessive-compulsive disorder. J Clin Psychiatry, 80:19f13163.
• APA (2013) Diagnostic and Statistical Manual of Mental Disorders Fifth edition (DSM-5.). Washington DC, American Psychiatric Association.
• Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA (2004) Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a preliminary study. Psychopharmacology (Berl), 174:530-538.
• Arrojo-Romero M, Tajes Alonso M, de Leon J (2013) Lamotrigine augmentation of serotonin reuptake inhibitors in severe and long-term treatment-resistant obsessive-compulsive disorder. Case Rep Psychiatry, 2013:612459.
• Atmaca M, Bingol I, Aydin A, Yıldırım H, Okur I, Yıldırım MA et al. (2010) Brain morphology of patients with body dysmorphic disorder. J Affect Disord, 123:258-263.
• Bakhla AK, Verma V, Soren S, Sarkhel S, Chaudhury S (2013) An open-label trial of memantine in treatment-resistant obsessive-compulsive disorder. Ind Psychiatry J, 22:149-152.
• Barroso L, Sternberg F, Souza M, Nunes G (2017) Trichotillomania: a good response to treatment with N-acetylcysteine. An Bras Dermatol, 92:537–539.
• Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, et al. (1995) Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage, 10:89-97.
• Berlin HA, Koran LM, Jenike MA, Shapira NA, Chaplin W, Pallanti S et al. (2011) Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry, 72:716–721.
• Bisol LW, Lara DR (2009) Improvement of obsessive-compulsive disorder with divalproex and lamotrigine in two patients with bipolar II disorder. Pharmacopsychiatry, 42:37–39.
• Bloch MH, Wasylink S, Landeros-Weisenberger A, Panza KE, Billingslea E, Leckman JF et al. (2012) Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biol Psychiatry, 72:964–970.
• Bloch MH, Panza KE, Grant JE, Pittenger C, Leckman JF (2013) N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial. J Am Acad Child Adolesc Psychiatry, 52:231-240.
• Bonnot O, Cohen D, Thuilleaux D, Consoli A, Cabal S, Tauber M (2016) Psychotropic treatments in Prader-Willi syndrome: a critical review of published literature. Eur J Pediatr, 175:9-18.
• Borue X, Sharma M, Hudak R (2015) Biological treatments for obsessive-compulsive and related disorders. J Obsessive Compuls Relat Disord, 6:7-26.
• Bruno A, Micò U, Pandolfo G, Mallamace D, Abenavoli E, Di Nardo F et al. (2012) Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder: a double-blind, placebo-controlled study. J Psychopharmacol, 26:1456–1462.
• Burguière E, Monteiro P, Mallet L, Feng G, Graybiel AM (2015) Striatal circuits, habits, and implications for obsessive-compulsive disorder. Curr Opin Neurobiol, 30:59-65.
• Castle D, Beilharz F, Phillips KA , Brakoulias V, Drummond LM , Hollander E et al. (2021) Body dysmorphic disorder: a treatment synthesis and consensus on behalf of the International College of Obsessive-Compulsive Spectrum Disorders and the Obsessive Compulsive and Related Disorders Network of the European College of Neuropsychopharmacology. Int Clin Psychopharmacol, 36:61-75.
• Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH et al. (2003) Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major depressive disorder. Psychopharmacology (Berl), 167:219–220.
• Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G et al. (2005) Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: An open-label trial. Biol Psychiatry, 58:424–428.
• Coric V, Kelmendi B, Pittenger C, Wasylink S, Bloch MH, Green J (2007) Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with trichotillomania. J Clin Psychiatry, 68:170-171.
• Costa DLC, Diniz JB, Requena G, Joaquim MA, Pittenger C, Bloch MH et al. (2017) Randomized, double-blind, placebo-controlled trial of N-Acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry, 78:e766-e773.
• de Salles Andrade JB, Giori IG, Melo-Felippe FB, Vieira-Fonseca T, Fontenelle LF, Kohlrausch FB (2019) Glutamate transporter gene polymorphisms and obsessive-compulsive disorder: A case-control association study. J Clin Neurosci, 62:53-59.
• Dong N, Nezgovorova V, Hong K, Hollander E (2019) Pharmacotherapy in body dysmorphic disorder: relapse prevention and novel treatments. Expert Opin Pharmacother, 20:1211–1219.
• Dougherty DD, Brennan BP, Stewart SE, Wilhelm S, Widge AS, Rauch SL (2018) Neuroscientifically informed formulation and treatment planning for patients with obsessive-compulsive disorder: A review. JAMA Psychiatry, 75:1081-1087.
• Dougherty D, Rauch S, Greenberg BD (2020) Pathophysiology of Obsessive-Compulsive and Related Disorders. In The American Psychiatric Association Publishing Textbook of Anxiety, Trauma and OCD-Related Disorders (Eds N Simon, E Hollander, BO Rothbaum, DJ Stein) 265-284. Washington DC, American Psychiatric Association Publishing.
• Emamzadehfard S, Kamaloo A, Paydary K, Ahmadipour A, Zeinoddini A, Ghaleiha A et al. (2016) Riluzole in augmentation of fluvoxamine for moderate to severe obsessive-compulsive disorder: Randomized, double-blind, placebo-controlled study. Psychiatry Clin Neurosci, 70: 332-341.
• Farnia V, Gharehbaghi H, Alikhani M, Almasi A, Golshani S, Tatari F et al. (2018) Efficacy and tolerability of adjunctive gabapentin and memantine in obsessive compulsive disorder: Double-blind, randomized, placebo controlled trial. J Psychiatr Res, 104:137-143.
• Farrell LJ, Waters AM, Boschen MJ, Hattingh L, McConnell H, Milliner EL et al. (2013) Difficult-to-treat pediatric obsessive compulsive disorder: feasibility and preliminary results of a randomized pilot trial of D-cycloserine augmented behavior therapy. Depress Anxiety, 30:723-731.
• Fineberg NA, Bienvenu OJ, Denys D, Lochner C, Nestadt G, Leckman JF et al. (2010) Should OCD be classified as an anxiety disorder in DSM-V? Depress Anxiety, 27:495-506.
• Gadallah AHA, Ebada MA, Gadallah A, Ahmed H, Rashad W, Eid KA et al. (2020) Efficacy and safety of N-acetylcysteine as add-on therapy in the treatment of obsessive-compulsive disorder: A systematic review and meta-analysis. J Obsessive Compuls Relat Disord, 25: 100529.
• Ghaderi A, Vahed N, Ghayoomi R, Ostadmohammadi V, Gholami M, Dehkohneh S (2019) N-acetylcysteine in addiction management: Current knowledge and future perspectives. International Journal of Pharmaceutical Research, 11:13-24.
• Ghaleiha A, Entezari N, Modabbernia A, Najand B, Askari N, Tabrizi M et al. (2013) Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study. J Psychiatr Res, 47:175-180.
• Ghanizadeh A, Mohammadi MR, Bahraini S, Keshavarzi Z, Firoozabadi A, Alavi Shoshtari A (2017) Efficacy of N-Acetylcysteine augmentation on obsessive compulsive disorder: A multicenter randomized double blind placebo controlled clinical trial. Iran J Psychiatry, 12:134-141.
• Grant P, Lougee L, Hirschtritt M, Swedo SE (2007a) An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol, 17:761–767.
• Grant JE, Odlaug BL, Kim SW (2007b) Lamotrigine treatment of pathologic skin picking: an open label study. J Clin Psychiatry, 68:1384–1391.
• Grant JE, Odlaug BL, Kim SW (2009) N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry, 66:756-763.
• Grant JE, Odlaug BL, Chamberlain SR, Kim SW (2010) A double-blind, placebo-controlled trial of lamotrigine for pathological skin picking: treatment efficacy and neurocognitive predictors of response. J Clin Psychopharmacol, 30:396-403.
• Grant JE, Odlaug BL, Chamberlain S, Kim SW (2011) Dronabinol, a cannabinoid agonist reduces hair pulling in trichotillomania: A pilot study. Psychopharmacology, 218:493–502.
• Grant PJ, Joseph LA, Farmer CA, Luckenbaugh DA, Lougee LC, Zarate CA Jr et al. (2014) 12-week, placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive-compulsive disorder. Neuropsychopharmacology, 39:1453-1459.
• Grant JE, Chamberlain SR, Redden SA, Leppink EW, Odlaug BL, Kim SW (2016) N-Acetylcysteine in the treatment of excoriation disorder: a randomized clinical trial. JAMA Psychiatry, 73:490–496.
• Grant JE, Chamberlain SR (2016) Trichotillomania. Am J Psychiatry, 173:868-874.
• Grant JE, Chesivoir E, Valle S, Ehsan D, Chamberlain SR (2023) Double-blind placebo-controlled study of memantine in trichotillomania and skin-picking disorder. Am J Psychiatry, 180:348-356.
• Golubchik P, Sever J, Weizman A, Zalsman G (2011) Methylphenidate treatment in pediatric patients with attention-deficit/hyperactivity disorder and comorbid trichotillomania: a preliminary report. Clinical Neuropharmacology, 34:108–110.
• Grados MA, Atkins EB, Kovacikova GI, McVicar E (2015) A selective review of glutamate pharmacological therapy in obsessive-compulsive and related disorders. Psychol Res Behav Manag, 8:115-131.
• Greenberg WM, Benedict MM, Doerfer J, Perrin M, Panek L, Cleveland WL et al. (2009) Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults. J Psychiatr Res, 43:664–670.
• Goodman WK, Storch EA, Sheth SA (2021) Harmonizing the neurobiology and treatment of obsessive-compulsive disorder. Am J Psychiatry, 178:17-29.
• Grünblatt E (2021) Genetics of OCD and related disorders; searching for shared factors. Curr Top Behav Neurosci, 49:1-16.
• Hadi F, Kashefinejad S, Kamalzadeh L, Hoobehfekr S, Shalbafan M (2021) Glutamatergic medications as adjunctive therapy for moderate to severe obsessive-compulsive disorder in adults: a systematic review and meta-analysis. BMC Pharmacol Toxicol, 22:69.
• Haghighi M, Jahangard L, Mohammad-Beigi H, Bajoghli H, Hafezian H, Rahimi A et al. (2013) In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl), 228:633-640.
• Isobe M, Redden SA, Keuthen NJ, Stein DJ, Lochner C, Grant JE, Chamberlain SR (2018) Striatal abnormalities in trichotillomania: a multi-site MRI analysis. Neuroimage Clin, 17:893-898.
• Jafferany M, Shireen F, Ibrahim A (2010) An open-label trial of topiramate in the treatment of skin picking in pervasive developmental disorder not otherwise specified. Prim Care Companion J Clin Psychiatry, 12:PCC.09l00829.
• Jafferany M, Osuagwu FC (2017) Use of topiramate in skin picking disorder: a pilot study. Prim Care Companion CNS Disord, 19:10.4088/PCC.16m01961.
• Khalkhali M, Aram S, Zarrabi H, Kafie M, Heidarzadeh A (2016) Lamotrigine augmentation versus placebo in serotonin reuptake inhibitors-resistant obsessive-compulsive disorder: a randomized controlled trial. Iran J Psychiatry, 11:104–114.
• Kress VE, Stargell NA, Zoldan CA, Paylo MJ (2016) Hoarding disorder: Diagnosis, assessment, and treatment. J Couns Dev, 94:83-90.
• Köse S, Çetin M (2017) Ketamine and rapastinel: NMDA receptor modulators in the rapid treatment of obsessivecompulsive disorder. Psychiatry Clin Psychopharmacol, 27:213–214.
• Kushner MG, Kim SW, Donahue C, Thuras P, Adson D, Kotlyar M (2007) D-cycloserine augmented exposure therapy for obsessive-compulsive disorder. Biol Psychiatry, 62:835-838.
• Lee TM, Lee KM, Lee CY, Lee HC, Tam KW, Loh EW (2021) Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials. Aust N Z J Psychiatry, 55:196-206.
• Lewin AB, Wu MS, McGuire JF, Storch EA (2014) Cognitive behavior therapy for obsessive-compulsive and related disorders. Psychiatr Clin North Am, 37:415-445.
• Lochner C, Seedat S, Niehaus DJ, Stein DJ (2006) Topiramate in the treatment of trichotillomania: an open-label pilot study. Int Clin Psychopharmacol, 21:255-259.
• Lochner C, Stein DJ (2014)Treatment of obsessive-compulsive and related disorders. Curr Treat Options Psychiatry, 1:225-234.
• Lochner C, Roos A, Stein DJ (2017) Excoriation (skin-picking) disorder: a systematic review of treatment options. Neuropsychiatr Dis Treat, 13:1867-1872.
• Lu S, Nasrallah HA (2018) The use of memantine in neuropsychiatric disorders: an overview. Ann Clin Psychiatry, 30:234–248.
• Maia TV, Cooney RE, Peterson BS (2008) The neural bases of obsessive - Compulsive disorder in children and adults. Dev Psychopathol, 20:1251–1283.
• Mataix-Cols D, Frost RO, Pertusa A, Clark LA, Saxena S, Leckman JF et al. (2010) Hoarding disorder: a new diagnosis for DSM-V?. Depress Anxiety, 27: 556–572.
• Mataix-Cols D, Turner C, Monzani B, Isomura K, Murphy C, Krebs G et al. (2014) Cognitive behavioral therapy with post-session D-cycloserine augmentation for pediatric obsessive compulsive disorder: pilot randomised controlled trial. Br J Psychiatry, 204:77-78.
• Marinova Z, Chuang DM, Fineberg N (2017) Glutamate-Modulating Drugs as a potential therapeutic strategy in obsessive-compulsive disorder. Curr Neuropharmacol, 15:977-995.
• Miller JL, Angulo M (2014) An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome. Am J Med Genet A, 164:421–424.
• Modarresi A, Sayyah M, Razooghi S, Eslami K, Javadi M, Kouti L (2018) Memantine augmentation improves symptoms in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder: A randomized controlled trial. Pharmacopsychiatry, 51:263-269.
• Modarresi A, Chaibakhsh S, Koulaeinejad N, Koupaei SR (2019) A systematic review and meta-analysis: memantine augmentation in moderate to severe obsessive-compulsive disorder. Psychiatry Research, 282:112602
• Mowla A, Khajeian AM, Sahraian A, Chohedri AH, Kashkoli F (2010) Topiramate augmentation in resistant OCD: A Double-blind placebo-controlled clinical trial. CNS Spectr, 15:613–617.
• Nakao T, Kanba S (2019) Pathophysiology and treatment of hoarding disorder. Psychiatry Clin Neurosci, 73:370-375.
• Nery FG, Li W, Del Bello MP, Welge JA (2021) N‐acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta‐analysis of randomized controlled trials. Bipolar Disord, 23:707-714.
• Niciu MJ, Kelmendi B, Sanacora G (2012) Overview of glutamatergic neurotransmission in the nervous system. Pharmacol Biochem Behav, 100:656–664.
• Nordstrom EJ, Burton FH (2002) A transgenic model of comorbid Tourette’s syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry, 7:617–625.
• Odlaug BL, Grant JE (2007) N-acetyl cysteine in the treatment of grooming disorders. J Clin Psychopharmacol, 27:227–229.
• Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M et al. (2015) N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci, 13:12–24.
• Özcan D, Seçkin D (2016) N-Acetylcysteine in the treatment of trichotillomania: remarkable results in two patients. J Eur Acad Dermatol Venereol, 30:1606-1608.
• Parli GM, Gales MA, Gales BJ (2023) N-Acetylcysteine for obsessive-compulsive and related disorders in children and adolescents: A review. Ann Pharmacother, 57:847-854.
• Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, Emamzadehfard S, Akhondzadeh S (2016) N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther, 41:214-219.
• Pietrzak B, Konopka A, Wojcieszak J (2013) Effect of topiramate on hippocampus-dependent spatial memory in rats. Pharmacol Rep, 65:1152-1162.
• Pittenger C, Bloch MH, Williams K (2011) Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment. Pharmacol Ther, 132:314–332.
• Pittenger C, Bloch MH, Wasylink S, Billingslea E, Simpson R, Jakubovski E (2015) Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: A pilot randomized placebo-controlled trial. J Clin Psychiatry, 76:1075–1084.
• Pittenger C (2015) Glutamatergic agents for OCD and related disorders. Curr Treat Options Psychiatry, 2:271-283.
• Poyurovsky M, Glick I, Koran LM (2010) Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive-compulsive symptoms. J Psychopharmacol, 24:861–866.
• Rauch SL, Phillips KA, Segal E, Makris N, Shin LM, Whalen PJ et al. (2003) A preliminary morphometric magnetic resonance imaging study of regional brain volumes in body dysmorphic disorder. Psychiatry Res, 122:13-19.
• Reddy YJ, Sundar AS, Narayanaswamy JC, Math SB (2017) Clinical practice guidelines for obsessive-compulsive disorder. Indian J Psychiatry, 59(Suppl 1):S74.
• Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D et al. (2013) Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology, 38:2475–2483.
• Rodriguez CI, Wheaton M, Zwerling J, Steinman SA, Sonnenfeld D, Galfalvy H et al. (2016) Can exposure-based CBT extend the effects of intravenous ketamine in obsessive-compulsive disorder? An open-label trial. J Clin Psychiatry, 77:408–409.
• Rotge JY, Aouizerate B, Tignol J, Bioulac B, Burbaud P, Guehl D (2010) The glutamate-based genetic immune hypothesis in obsessive-compulsive disorder. An integrative approach from genes to symptoms. Neuroscience, 165:408–417.
• Sani G, Gualtieri I, Paolini M, Bonanni L, Spinazzola E, Maggiora M et al. (2019) Drug treatment of trichotillomania (hair-pulling disorder), excoriation (skin-picking) disorder, and nail-biting (onychophagia). Curr Neuropharmacol, 17:775-786.
• Sarris J, Oliver G, Camfield DA, Dean OM, Dowling N, Smith DJ et al. (2015) N-Acetyl Cysteine (NAC) in the treatment of obsessive-compulsive disorder: A 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs, 29:801-809.
• Sasso DA, Kalanithi PS, Trueblood KV, Pittenger C, Kelmendi B, Wayslink S et al (2006) Beneficial effects of the glutamate-modulating agent riluzole on disordered eating and pathological skin-picking behaviors. J Clin Psychopharmacol, 26:685–687.
• Shapira NA, Lessig MC, Murphy TK, Driscoll DJ, Goodman WK (2002) Topiramate attenuate self-injurious behavior in Prader-Willi syndrome. Int J Neuropsychopharmacol, 5:141–145.
• Shmelkov SV, Hormigo A, Jing D, Proenca CC, Bath KG, Milde T et al (2010) Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med, 16:598-602.
• Silva-Netto R, Jesus G, Nogueira M, Tavares H (2014) N-Acetylcysteine in the treatment of skin picking disorder. Braz J Psychiatr, 36:101.
• Suzuki K, Monteggia LM (2020) The role of eEF2 kinase in the rapid antidepressant actions of ketamine. Adv Pharmacol, 89:79-99.
• Stein DJ, Fineberg NA, Bienvenu OJ, Denys D, Lochner C, Nestadt G et al. (2010) Should OCD be classified as an anxiety disorder in DSM-V? Depress Anxiety, 27:495–506.
• Stewart SE, Fagerness JA, Platko J, Smoller JW, Scharf JM, Illmann C et al. (2007) Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet, 144B:1027–1033.
• Stewart SE, Jenike EA, Hezel DM, Stack DE, Dodman NH, Shuster L et al. (2010) A single-blinded case-control study of memantine in severe obsessive-compulsive disorder. J Clin Psychopharmacol, 30:34–39.
• Storch EA, Merlo LJ, Bengtson M, Murphy TK, Lewis MH, Yang MC et al. (2007) D-cycloserine does not enhance exposure-response prevention therapy in obsessive-compulsive disorder. Int Clin Psychopharmacol, 22:230-237.
• Storch EA, Murphy TK, Goodman WK, Geffken GR, Lewin AB, Henin A et al. (2010) A preliminary study of D-cycloserine augmentation of cognitive behavioral therapy in pediatric obsessive-compulsive disorder. Biol Psychiatry, 68:1073-1076.
• Storch EA, Wilhelm S, Sprich S, Henin A, Micco J, Small BJ et al. (2016) Efficacy of augmentation of cognitive behavior therapy with weight- adjusted d-Cycloserine vs placebo in pediatric obsessive-compulsive disorder: A randomized clinical trial. JAMA Psychiatry, 73:779-788.
• Suppes T (2002) Review of the use of topiramate for treatment of bipolar disorders. J Clin Psychopharmacol, 22:599–609.
• Ting JT, Feng G (2008) Glutamatergic synaptic dysfunction and obsessive-compulsive disorder. Curr Chem Genomics, 2:62–75.
• Torales J, Ruiz Díaz N, Ventriglio A, Castaldelli-Maia JM, Barrios I, García O et al. (2021) Hair-pulling disorder (Trichotillomania): Etiopathogenesis, diagnosis and treatment in a nutshell. Dermatol Ther, 34:e13466.
• Uzun O (2010) Lamotrigine as an augmentation agent in treatment-resistant obsessive-compulsive disorder: A case report. J Psychopharmacol, 24:425–427.
• Van Ameringen M, Patterson B, Simpson W (2014) DSM‐5 obsessive‐compulsive and related disorders: Clinical implications of new criteria. Depress Anxiety, 31:487-493.
• Verrotti A, Striano P, Iapadre G, Zagaroli L, Bonanni P, Coppola G et al. (2018) The pharmacological management of Lennox-Gastaut syndrome and critical literature review. Seizure, 63:17–25.
• Vlček P, Polák J, Brunovský M, Horáček J (2018) Role of glutamatergic system in obsessive-compulsive disorder with possible therapeutic implications. Pharmacopsychiatry, 51:229-242.
• Welch JM, Lu J, Rodriguiz RM, Trotta NC, Peca J, Ding JD et al. (2007) Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature, 448:894–900.
• Wilhelm S, Buhlmann U, Tolin DF, Meunier SA, Pearlson GD, Reese HE et al. (2008) Augmentation of behavior therapy with D-cycloserine for obsessive-compulsive disorder. Am J Psychiatry, 165: 335-341.
• Wu K, Hanna GL, Rosenberg DR, Arnold PD (2012) The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav, 100:726–735.
• Xia J, Du Y, Han J, Liu G, Wang X (2015) D-cycloserine augmentation in behavioral therapy for obsessive-compulsive disorder: a meta-analysis. Drug Des Devel Ther, 9:2101-2117.
• Yolland CO, Hanratty D, Neill E, Rossell SL, Berk M, Dean OM et al. (2020) Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia. Aust N Z J Psychiatry, 54: 453-466.