Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial

Kapoor, Raju; Furby, J; Hayton, Tom; Smith, Kenneth J.; Altmann, Daniel R.; Brenner, Robert; Chataway, Jeremy; Hughes, Richard; Miller, David H.

doi:10.1016/s1474-4422(10)70131-9

Cited by 271 publications

(222 citation statements)

References 31 publications

Supporting

Mentioning

211

Contrasting

Unclassified

Order By: Relevance

“…Indeed, patients with lamotrigine had significantly higher concentrations than controls, whereas patients without lamotrigine did not differ from controls. This finding accords findings from a clinical trial in which a neuroprotective effect of lamotrigine was tested in MS patients (Kapoor et al, 2010). Interestingly, the findings were negative and lamotrigine treatment was instead associated with white matter volume loss.…”

Section: Discussionsupporting

confidence: 87%

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Jakobsson

Bjerke

Ekman

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs.

show abstract

Section: Discussionsupporting

confidence: 87%

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Jakobsson

Bjerke

Ekman

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…However, the rate of decline on Timed 25-Foot Walk speed assessments was reduced in the treatment group compared with placebo [110]. The interpretation of the results was also further complicated by a nonadherence rate of up to 50 % in lamotrigine group.…”

Section: Phenytoin and Oxcarbazepinementioning

confidence: 88%

“…In a phase II trial of lamotrigine versus placebo in patients with SPMS, lamotrigine treatment was unexpectedly found to be associated with greater annual cerebral volume loss in the first year compared with placebo; an effect reversed partially on discontinuation of treatment [110]. However, the rate of decline on Timed 25-Foot Walk speed assessments was reduced in the treatment group compared with placebo [110].…”

Section: Phenytoin and Oxcarbazepinementioning

confidence: 97%

Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis

2016

View full text Add to dashboard Cite

Identifying effective therapies for the treatment of progressive forms of multiple sclerosis (MS) is a highly relevant priority and one of the greatest challenges for the global MS community. Better understanding of the mechanisms involved in progression of the disease, novel trial designs, drug repurposing strategies, and new models of collaboration may assist in identifying effective therapies. In this review, we discuss various therapies under study in phase II or III trials, including antioxidants (idebenone); tyrosine kinase inhibitors ( m a s i t i n i b ) ; s p h i n g o s i n e r e c e p t o r m o d u l a t o r s (siponimod); monoclonal antibodies (anti-leucine-rich repeat and immunoglobulin-like domain containing neurite outgrowth inhibitor receptor-interacting protein-1, natalizumab, ocrelizumab, intrathecal rituximab); hematopoetic stem cell therapy; statins and other possible neuroprotective agents (amiloride, riluzole, fluoxetine, oxcarbazepine); lithium; phosphodiesterase inhibitors (ibudilast); hormone-based therapies (adrenocorticotrophic hormone and erythropoietin); T-cell receptor peptide vaccine (NeuroVax); autologous T-cell immunotherapy (Tcelna); MIS416 (a microparticulate immune response modifier); dopamine antagonists (domperidone); and nutritional supplements, including lipoic acid, biotin, and sunphenon epigallocatechin-3-gallate (green tea extract). Given ongoing and planned clinical trial initiatives, and the largest ever focus of the global research community on progressive MS, future prospects for developing targeted therapeutics aimed at reducing disability in progressive forms of MS appear promising.

show abstract

“…Interestingly, when the study was repeated using either phenytoin or carbamazepine, another antiepileptic with Na + channel blocker capacities, the animals became acutely worse after the withdrawal of either drug [121], indicating that more work needs to be done to understand the consequences of the long-term effects of Na + channel blockers and of their withdrawal in MS. Two other Na + -blocking agents, the antiarrhythmic agent flecainide and the antiepileptic lamotrigine, have now been shown to improve axonal survival and decrease disability in EAE-affected rats [122,123]. However, in a Phase II study in patients with secondary progressive disease course, lamotrigine showed an increase of cerebral volume loss which was not clinically relevant, but could not be explained [123]. This 'pseudoatrophy', seen in the early stages of this trial under lamotrigine treatment, indicates that the choice of this trial end point was not adequate.…”

Section: Promising Therapeutic Concepts With Putative Neuroprotectivementioning

confidence: 99%

Neurodegeneration in multiple sclerosis: novel treatment strategies

Luessi

Siffrin

Zipp³

2012

Expert Review of Neurotherapeutics

View full text Add to dashboard Cite

In recent years it has become clear that the neuronal compartment already plays an important role early in the pathology of multiple sclerosis (MS). Neuronal injury in the course of chronic neuroinflammation is a key factor in determining long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protection and repair needed in addition to controlling inflammation. Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies. Neurodegeneration in multiple sclerosis: novel treatment strategiesExpert Rev. Neurother. 12(9), 1061-1077 (2012) Keywords: multiple sclerosis • neurodegeneration • neuronal injury • neuroprotection • treatment Medscape: Continuing Medical Education OnlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Expert Reviews Ltd. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at www.medscape.org/journal/expertneurothera; (4) view/print certificate. Learning objectivesUpon completion of this activity, participants will be able to:• Describe recent insights into inflammatory neuronal injury in multiple sclerosis, based on a review • Describe methods of quantification of neuronal injury in patients with multiple sclerosis, based on a review • Describe applications of these findings to treatment for patients with multiple sclerosis, based on a review

show abstract

Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial

Cited by 271 publications

References 31 publications

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis

Neurodegeneration in multiple sclerosis: novel treatment strategies

Contact Info

Product

Resources

About