Role of Lamotrigine Augmentation in Treatment-Resistant Obsessive Compulsive Disorder: A Retrospective Case Review from South Asia

Hussain, Arshad; Dar, Mansoor Ahmad; Wani, Rayees Ahmad; Shah, Majid Shafi; Jan, Mohd Muzzaffar; Malik, Yasir A; Chandel, Rajesh Kumar; Margoob, Mushtaq Ahmad

doi:10.4103/0253-7176.155613

Cited by 10 publications

(3 citation statements)

References 18 publications

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“…It blocks voltage-gated sodium channels, thus inhibiting glutamate release, inhibits AMPA receptors, is an indirect inhibitor of histone deacetylases (HDACs) and robustly induces the prominent neuroprotective protein Bcl-2 [ 109 ]. Positive results from case reports [ 110 - 112 ], and a retrospective open-label case series of 22 adult treatment-resistant OCD patients [ 113 ] suggested a possible therapeutic role for lamotrigine in OCD. On the other hand, in another case series of 8 treatment-resistant OCD patients, adjunctive lamotrigine resulted in significant improvement in only one patient [ 114 ].…”

Section: Resultsmentioning

confidence: 99%

Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder

Marinova

Chuang

Fineberg

2017

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Objective: Abstract: Obsessive-compulsive disorder (OCD) is a mental disease commonlyassociated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients.Methods: We conducted a search of the MEDLINE database for clinical studies evaluating theeffect of glutamate-modulating drugs in OCD.Results:Memantine is the compound most consistently showing a positive effect as an augmentation therapy in OCD. Anti-convulsant drugs (lamotrigine, topiramate) and riluzole may also provide therapeutic benefit to some OCD patients. Finally, ketamine may be of interest due to its potential for a rapid onset of action.Conclusion: Further randomized placebo-controlled trials in larger study populations are necessary in order to draw definitive conclusions on the utility of glutamate-modulating drugs in OCD.Furthermore, genetic and epigenetic factors, clinical symptoms and subtypes predicting treatment response to glutamate-modulating drugs need to be investigated systematically.

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Section: Resultsmentioning

confidence: 99%

Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder

Marinova

Chuang

Fineberg

2017

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“…In human studies, have evidenced that 16 weeks of treatment with LAM in obsessive-compulsive patients significantly reduced the Y-BOCS scores, as well as the Hamilton Rating Scale for Depression scores and the Clinical Global Impression-Severity scores (Bruno et al, 2012). More recently, two other studies using adjunctive treatment of LAM in addition to SRIs treatment led in treatment-resistant OCD patients during 8 and 12 weeks respectively, revealed a greater reduction in total YBOCS scores in LAM group (Hussain et al, 2015; Khalkhali et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Increased Fear Memory and Glutamatergic Modulation in Compulsive Drinker Rats Selected by Schedule-Induced Polydipsia

Prados-Pardo

Martín-González

Mora

et al. 2019

Front. Behav. Neurosci.

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Compulsive behavior is observed in several neuropsychiatric disorders such as obsessive-compulsive disorder (OCD), anxiety, depression, phobia, and schizophrenia. Thus, compulsivity has been proposed as a transdiagnostic symptom with a highly variable pharmacological treatment. Recent evidence shows that glutamate pharmacotherapy may be of benefit in impaired inhibitory control. The purpose of the present study was: first, to test the comorbidity between compulsivity and other neuropsychiatric symptoms on different preclinical behavioral models; second, to assess the therapeutic potential of different glutamate modulators in a preclinical model of compulsivity. Long Evans rats were selected as either high (HD) or low (LD) drinkers corresponding with their water intake in schedule-induced polydipsia (SIP). We assessed compulsivity in LD and HD rats by marble burying test (MBT), depression by forced swimming test (FST), anxiety by elevated plus maze (EPM) and fear behavior by fear conditioning (FC) test. After that, we measured the effects of acute administration (i.p.) of glutamatergic drugs: N-Acetylcysteine (NAC; 25, 50, 100 and 200 mg/kg), memantine (3.1 and 6.2 mg/kg) and lamotrigine (15 and 30 mg/kg) on compulsive drinking on SIP. The results obtained showed a relation between high compulsive drinking on SIP and a higher number of marbles partially buried in MBT, as well as a higher percentage of freezing on the retrieval day of FC test. We did not detect any significant differences between LD and HD rats in FST, nor in EPM. The psychopharmacological study of glutamatergic drugs revealed that memantine and lamotrigine, at all doses tested, decreased compulsive water consumption in HD rats compared to LD rats on SIP. NAC did not produce any significant effect on SIP. These results indicate that the symptom clusters of different forms of compulsivity and phobia might be found in the compulsive phenotype of HD rats selected by SIP. The effects of memantine and lamotrigine in HD rats point towards a dysregulation in the glutamatergic signaling as a possible underlying mechanism in the vulnerability to compulsive behavior on SIP. Further studies on SIP, could help to elucidate the therapeutic role of glutamatergic drugs as a pharmacological strategy on compulsive spectrum disorders.

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“…It blocks voltage-gated sodium channels, thus inhibiting glutamate release, inhibits AMPA receptors, is an indirect inhibitor of histone deacetylases (HDACs) and robustly induces the prominent neuroprotective protein Bcl-2 [109]. Positive results from case reports [110][111][112], and a retrospective open-label case series of 22 adult treatment-resistant OCD patients [113] suggested a possible therapeutic role for lamotrigine in OCD. On the other hand, in another case series of 8 treatment-resistant OCD patients, adjunctive lamotrigine resulted in significant improvement in only one patient [114].…”

Section: Lamotriginementioning

confidence: 99%

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

Marinova¹

2016

Preprint

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Objective: Obsessive-compulsive disorder (OCD) is a mental disease commonly associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients. Methods: We conducted a search of the MEDLINE database for clinical studies evaluating the effect of glutamate-modulating drugs in OCD. Results: Memantine is the compound most consistently showing a positive effect as an augmentation therapy in OCD. Anti-convulsant drugs (lamotrigine, topiramate) and riluzole may also provide therapeutic benefit to some OCD patients. Finally, ketamine may be of interest due to its potential for a rapid onset of action. Conclusion: Further randomized placebo-controlled trials in larger study populations are necessary in order to draw definitive conclusions on the utility of glutamate-modulating drugs in OCD. Furthermore, genetic and epigenetic factors, clinical symptoms and subtypes predicting treatment response to glutamate-modulating drugs need to be investigated systematically.

show abstract

Role of Lamotrigine Augmentation in Treatment-Resistant Obsessive Compulsive Disorder: A Retrospective Case Review from South Asia

Cited by 10 publications

References 18 publications

Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder

Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder

Increased Fear Memory and Glutamatergic Modulation in Compulsive Drinker Rats Selected by Schedule-Induced Polydipsia

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

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