Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder

Marinova, Zoya

doi:10.26226/morressier.5785edcfd462b80296c99eca

Cited by 4 publications

(4 citation statements)

References 77 publications

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“…Another system probably involved in OCD is the glutamatergic system. The glutamate-modulating drugs have recently been investigated as potentially new treatment targets for this disorder (Marazziti et al, 2018; Marinova et al, 2017; Pittenger et al, 2011; Rajendram et al, 2017). Since 5-HT 3 receptor antagonists have glutamate modulating effects through antagonizing inhibitory effects of 5-HT 3 receptors on N-methyl-d-aspartate (NMDA) receptors, they could exert their obsession and compulsion attenuating properties in this pathway.…”

Section: Discussionmentioning

confidence: 99%

Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial

et al. 2019

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Background: About 50% of obsessive-compulsive disorder patients still suffer significant symptoms even after the recommended first-line therapy. This demonstrates the necessity to investigate strategies to improve alleviation of symptoms. Objective: The main objective of this study was to investigate the efficacy of a 5-hydroxytryptophan 3 receptor antagonist, tropisetron, as an adjuvant therapy to selective serotonin reuptake inhibitors, in ameliorating obsessive-compulsive disorder symptoms. Methods: Men and women between the ages of 18–60 years diagnosed with obsessive-compulsive disorder, based on DSM5, who had a Yale-Brown obsessive compulsive scale score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either tropisetron (5 mg twice daily) and fluvoxamine (100 mg daily initially followed by 200 mg daily after week 4) or placebo and fluvoxamine. The primary outcome of interest in this study was the Yale-Brown obsessive compulsive scale total score decrease from baseline. Results: One hundred and eight participants were equally randomized into two groups; 48 participants in each group finished the trial. The Yale-Brown obsessive compulsive total score significantly dropped in both groups while the tropisetron group participants experienced a significantly higher decrease in their scores (Greenhouse-Geisser F(1.53–65.87)=3.516, p-value=0.04). No major adverse effect was observed in any of the groups. Conclusion: This trial showed a significant efficacy for tropisetron over placebo in treatment of obsessive-compulsive disorder symptoms when added to fluvoxamine.

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Section: Discussionmentioning

confidence: 99%

Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial

et al. 2019

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“…A recent meta-analysis found that memantine showed positive effects as an augmentation therapy in OCD (Modarresi, Chaibakhsh, Koulaeinejad, & Koupaei, 2019). Moreover, glutamatergic anticonvulsant drugs (lamotrigine and topiramate) and riluzole may provide therapeutic benefits to some OCD patients (Marinova, Chuang, & Fineberg, 2017). Ketamine, an N -methyl- d -aspartate receptor antagonist, may also be of interest due to its potential for a rapid onset of action, but further randomized placebo-controlled trials in larger study populations are necessary to draw definitive conclusions.…”

Section: Clinical and Therapeutic Implicationsmentioning

confidence: 99%

Genetics of obsessive-compulsive disorder

et al. 2021

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Background Obsessive-compulsive disorder (OCD) is a psychiatric disorder with multiple symptom dimensions (e.g. contamination, symmetry). OCD clusters in families and decades of twin studies clearly demonstrate an important role for genetics in the etiology of the disorder. Methods In this review, we summarize the genetic epidemiology and molecular genetic studies of OCD and obsessive-compulsive symptoms. Results OCD is a heritable, polygenic disorder with contributions from both common and rare variants, including de novo deleterious variations. Multiple studies have provided reliable support for a large additive genetic contribution to liability to OCD, with discrete OCD symptom dimensions having both shared and unique genetic risks. Genome-wide association studies have not produced significant results yet, likely because of small sample sizes, but larger meta-analyses are forthcoming. Both twin and genome-wide studies show that OCD shares genetic risk with its comorbid conditions (e.g. Tourette syndrome and anorexia nervosa). Conclusions Despite significant efforts to uncover the genetic basis of OCD, the mechanistic understanding of how genetic and environmental risk factors interact and converge at the molecular level to result in OCD's heterogeneous phenotype is still mostly unknown. Future investigations should increase ancestral genetic diversity, explore age and/or sex differences in genetic risk for OCD and expand the study of pharmacogenetics, gene expression, gene × environment interactions and epigenetic mechanisms for OCD.

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“…3 Based on this premise, signs of FHS should diminish and/or disappear after initiation of behaviour modification and/or treatment with psychoactive medications such as selective serotonin reuptake inhibitors (SSRIs; eg, fluoxetine) or tricyclic antidepressants (eg, clomipramine or amitriptyline), and glutamate-modulating medications (eg, topiramate and gabapentin) (see Figure 2). 3,8 Although in some cases this therapeutic approach might be satisfactory, in our study 2/4 cats achieved remission of clinical signs only after anti-inflammatory or immunosuppressive medications were added to psychotropic drugs.…”

Section: Discussionmentioning

confidence: 50%

Feline hyperaesthesia syndrome with self-trauma to the tail: retrospective study of seven cases and proposal for an integrated multidisciplinary diagnostic approach

Batle

Rusbridge

Nuttall

et al. 2018

Journal of Feline Medicine and Surgery

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Case series summary This was a retrospective study on the clinical features and response to treatment in seven cats with feline hyperaesthesia syndrome (FHS) and tail mutilation. FHS is a poorly understood disorder characterised by skin rippling over the dorsal lumbar area, episodes of jumping and running, excessive vocalisation, and tail chasing and self-trauma. The majority of the cats were young, with a median age of 1 year at the onset of clinical signs, male (n = 6) and with access to the outdoors (n = 5). Multiple daily episodes of tail chasing and self-trauma were reported in five cats, with tail mutilation in four cats. Vocalisation during the episodes (n = 5) and rippling of lumbar skin (n = 5) were also reported. Haematology, serum biochemistry, Toxoplasma gondii and feline immunodeficiency virus/feline leukaemia virus serology, MRI scans of brain, spinal cord and cauda equina, cerebrospinal fluid analysis and electrodiagnostic tests did not reveal any clinically significant abnormalities. A definitive final diagnosis was not reached in any of the cats, but hypersensitivity dermatitis was suspected in two cases. A variety of medications was used alone or in combination, including gabapentin (n = 6), meloxicam (n = 4) antibiotics (n = 4), phenobarbital (n = 2), prednisolone (n = 2) and topiramate (n = 2); ciclosporin, clomipramine, fluoxetine, amitriptyline and tramadol were used in one cat each. Clinical improvement was achieved in six cases; in five cats complete remission of clinical signs was achieved with gabapentin alone (n = 2), a combination of gabapentin/ciclosporin/amitriptyline (n = 1), gabapentin/prednisolone/phenobarbital (n = 1) or gabapentin/topiramate/meloxicam (n = 1). Relevance and novel information This is the first retrospective study on a series of cats with FHS. The diagnostic work-up did not reveal any significant abnormalities of the central or peripheral nervous system; dermatological and behavioural problems could not be ruled out. We propose an integrated multidisciplinary diagnostic pathway to be used for the management of clinical cases and for future prospective studies.

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Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder

Cited by 4 publications

References 77 publications

Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial

Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial

Genetics of obsessive-compulsive disorder

Feline hyperaesthesia syndrome with self-trauma to the tail: retrospective study of seven cases and proposal for an integrated multidisciplinary diagnostic approach

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