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

Year 2024, , 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

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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

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