Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Grassi, Giacomo; Cecchelli, Chiara; Vignozzi, Luisa; Pacini, Silvia

doi:10.2147/jep.s255375

Cited by 27 publications

(27 citation statements)

References 122 publications

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“…Antidopaminergic drugs were considered the first choice but they were found to be effective in a subset of patients. Recently, the role of glutamate and inflammation in OCD pathophysiology has emerged, and this has led to investigation on glutamatergic modulators and anti‐inflammatory agents (celecoxib) 92 . The recent evidence of the hyperactivity in the CSTC loop implies a high level of glutamate in the cortical‐striatal pathways as well as a dysregulation of GABAergic transmission in OCD.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive–compulsive disorder: A network meta‐analysis

Maiti

Mishra

Srinivasan

et al. 2023

Acta Psychiatr Scand

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Objectives The augmentation of serotonin reuptake inhibitors (SRIs) can be achieved by add‐on therapy with different pharmacological agents in obsessive–compulsive disorder (OCD) for a better clinical outcome. This network meta‐analysis (NMA) was conducted to evaluate and compare the effects of available augmentation agents for SRIs in OCD. Method The data was extracted from 59 relevant clinical trials after a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and clinical trial registries. PRISMA guidelines were followed in data extraction, analysis and reporting. Random effects Bayesian NMA was done to pool the effects across the interventions for the change in Yale‐Brown Obsessive–Compulsive Scale (YBOCS) scoring from baseline to the end of the study. Network graph was built, consistency model was run, node splitting analysis was performed, treatments were ranked as per SUCRA score and meta‐regression was done for refractoriness to SRIs and duration of augmentation therapy as the predictor variables. Results The drugs showing significant reduction in YBOCS scoring were pregabalin (MD:−8.1;95% CrI: −16, −0.43), memantine (MD:−6.2;95% CrI: −9.9, −2.3), lamotrigine (MD:−6;95% CrI: −12, −0.47), ondansetron (MD:−5.7;95% CrI: −11, −0.67), granisetron (MD:−5.6;95% CrI: −11, −0.44), aripiprazole (MD:−5.4;95% CrI:−9.1, −1.6), risperidone (MD:−3.3;95% CrI: −6.4, −0.20) and topiramate (MD:−5.3;95% CrI: −9.6, −0.97). The node‐split analysis showed that direct and indirect pooled effect sizes for all comparisons were comparable. Meta‐regression showed a statistically non‐significant association between YBOCS score reduction with the duration of augmentation therapy, but significant with SRI‐refractory status. Finally, the results were sorted based on certainty of evidence. Conclusion Memantine was found to be most effective augmentation agent for SRIs in OCD, followed by lamotrigine, ondansetron and granisetron with moderate certainty of evidence. The augmentation agents showed better symptom reduction in patients with SRI‐refractory OCD in comparison to non‐refractory OCD. PROSPERO registration CRD42022360110.

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Section: Discussionmentioning

confidence: 99%

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive–compulsive disorder: A network meta‐analysis

Maiti

Mishra

Srinivasan

et al. 2023

Acta Psychiatr Scand

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“…Successful completion of our aims will make important contributions to understanding the etiology of this disorder, alongside diversifying the sample to include understudied populations. We believe that the identification of specific genes and biological pathways mediating susceptibility to OCD will lead to improved detection, differential diagnosis, and treatment strategies (Grassi et al, 2020). Our sampling scheme is not only cost-effective; but also captures representative, comprehensively phenotyped Latinx OCD cases in multiple Latin American nations.…”

Section: Introductionmentioning

confidence: 99%

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol

Crowley

Cappi

OchoaPanaifo

et al. 2023

Preprint

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Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

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“…It may involve various factors such as genetic vulnerability, neurobiological dysfunction, and environmental influences. Recent research has also found that glutamate and inflammation could be involved in OCD [4] . The current OCD treatment options focus on serotonin imbalance and cognitive behavioral therapy [3] .…”

Section: Introductionmentioning

confidence: 99%

“…However, up to 40% of patients do not respond to selective serotonin reuptake inhibitors (SSRIs). Those who respond tend to require higher dosages of SSRIs than those used in depression [4] . Hence, there is an increased risk of dose-dependent adverse effects such as gastrointestinal symptoms and sexual dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, there is an increased risk of dose-dependent adverse effects such as gastrointestinal symptoms and sexual dysfunction. Meanwhile, only one-third of treatment-resistant OCD may respond to augmentation with antidopaminergic agents [4] . There is a need for research to understand the pathophysiological mechanisms of OCD further to discover new approaches for treatment-resistant OCD and augment existing therapies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gut Microbiome in Obsessive Compulsive Disorder: Potential of Probiotics as an Adjuvant Therapy

Kong¹,

Letchumanan²,

Tan³

et al. 2022

Prog Micobes Mol Biol

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The gut-brain axis concept has become an exciting area of research in psychiatry. Gastrointestinal inflammation and gut microbiome dysbiosis have been associated with mental health disorders. Obsessive-compulsive disorder (OCD) is a debilitating and complex mental illness that cannot be completely curable, stemming from many causes and risk factors. Generally, there is limited research on OCD and its association with the gut microbiome compared to other psychiatric conditions such as depression and anxiety. This review aims to provide insights into the association of gut microbiome and gastrointestinal inflammation with OCD. Besides, the role of probiotics as a potential therapy will be discussed in this review. The studies compiled in this review demonstrated variations in the gut microbial composition, often with lower microbial diversity in OCD patients compared to the controls. The gut microbiome is also involved in regulating the immune system. Alteration in certain groups of gut bacteria could give rise to inflammation and manifestations of gastrointestinal symptoms in OCD patients. As an approach to restoring the balance of the gut microbiome, probiotics serve as an effective solution. In vivo animal studies showed that probiotics can potentially improve OCD symptoms. Nevertheless, clinical trials are required to determine the efficacy of probiotics as an adjuvant therapy to alleviate OCD symptoms.

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Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Cited by 27 publications

References 122 publications

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive–compulsive disorder: A network meta‐analysis

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive–compulsive disorder: A network meta‐analysis

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol

Gut Microbiome in Obsessive Compulsive Disorder: Potential of Probiotics as an Adjuvant Therapy

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