topiramate and Dementia

The duration and, age of dementia have been linked to a higher risk of seizures. The exact mechanism that drives epileptogenesis in impaired mitophagy and autophagy linked dementia (MAD) is fully defined after reviewing the Scopus, Publon, and Pubmed databases. The epileptogenesis in patients with Alzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) is due to involvement of amyloid plaques (Aβ), phosphorylated tau (pTau), Parkin, NF-kB and NLRP3 inflammasome. Microglia, the prime protective and inflammatory cells in the brain exert crosstalk between mitophagy and inflammation. Several researchers believed that the inflammatory brain cells microglia could be a therapeutic target for the treatment of a MAD associated epilepsy. There are conventional antiepileptic drugs such as gabapentin, lamotrigine, phenytoin sodium, carbamazepine, oxcarbazepine, felbamate, lamotrigine, valproate sodium, and topiramate are prescribed by a psychiatrist to suppress seizure frequency. Also, the conventional drugs generate serious adverse effects and synergises dementia characteristics. The adverse effect of carbamazepine is neurotoxic and also, damages haemopoietic system and respiratory tract. The phenytoin treatment causes cerebellar defect and anemia. Dementia and epilepsy have a complicated relationship, thus targeting mitophagy for cure of epileptic dementia makes sense. Complementary and alternative medicine (CAM) is one of the rising strategies by many patients of the world, not only to suppress seizure frequency but also to mitigate dementia characteristics of patients. Therefore our present review focus on the interplay between epilepsy and MAD and their treatment with CAM approaches.

Topics: Anticonvulsants; Carbamazepine; Dementia; Epilepsy; Felbamate; Gabapentin; Humans; Inflammasomes; Lamotrigine; Mitophagy; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxcarbazepine; Parkinson Disease; Phenytoin; Seizures; Topiramate; Triazines; Ubiquitin-Protein Ligases; Valproic Acid

Dementia, besides the dominant cognitive disorders that define it, is associated with behavioral disturbances, the consequences of which are, on various levels, a determining factor for the handling of these patients. The treatment of behavioral and psychological symptoms is essential and although, to date, no therapeutic solution is satisfactory, it is necessary to look for an alternative to the neuroleptics usually employed, which raise real problems of tolerance in this geriatric population.. For several years, anticonvulsants, among which some have shown mood stabilizing activity, have been the object of research in this indication. The purpose of this review of the literature is to assess the interest and the limits of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate, oxcarbazepine) in the treatment of the so-called "noncognitive" symptoms of dementia. Their mechanism of action in mood disorders is not well known, but it would appear to be via the modulation of glutamate-mediated excitatory synaptic transmission and gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission that anticonvulsants might reduce behavioral symptoms in demented patients.. The method employed in this work was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labelled studies using validated scales were retained.. Among these medications, only carbamazepine demonstrated its efficacy in behavioral and psychological symptoms of dementia (BPSD) in controlled studies, notably that of Tariot et al. [J Am Geriatr Soc 42 (1994) 1160-1166 and Am J Psychiatry 155 (1998) 54-61] and Olin et al. [Am J Geriatr Psychiatry 9 (2001) 400-405], but with significant adverse events (sedation, hyponatremia, cardiac toxicity), particularly in the elderly and, being a strong enzymatic inducer, with a high likelihood of drug-drug interactions. Valproic acid showed some interesting results in BPSD within a large number of open studies and case reports. However, among the five controlled studies that have been published [Curr Ther Res 62 (2001) 51-67; Am J Geriatr Psychiatry 9 (2001) 58-66; Int J Geriatr Psychiatry 17 (2002) 579-585; Curr Alzheimer Res 2 (2005) 553-558 and Am J Geraitr Psychiatry 13 (2005) 942-945], none confirmed its efficacy on these symptoms. Regarding its tolerability in the geriatric population, no notable major side effect was reported (haematologic and hepatic effects are not more frequent than in the general population), except possible excessive sedation. Moreover, it appears that valproic acid could have neuroprotective effects, even if the contrary has been observed in a recent study. More studies need to be (and are being) conducted, notably on the interest of valproic acid in prophylaxis of BPSD. Gabapentin seems to be worthwhile and well tolerated in this indication, but no controlled study has been conducted to prove its efficacy, even if a quite important number of case reports and open studies have shown encouraging results. Concerning lamotrigine, which may potentially induce severe cutaneous side effects when administered with valproic acid, this drug has shown its efficacy in bipolar disorders and two recent case reports seem to indicate some interest in BPSD. Furthermore, lamotrigine appears to have neuroprotective effects. Although topiramate has shown interesting results in one open study in BPSD, its use in demented patients cannot be recommended because of its deleterious effect on cognitive functions. Oxcarbazepine, theoretically, could be an alternative to carbamazepine, which is, as aforesaid, the only anticonvulsant that proved its interest in BPSD. However, no clinical study has yet been published to support this hypothesis. This drug is better tolerated than carbamazepine, but induces severe and more frequent hyponatremia.. Finally, although we all know that antipsychotics should no longer be prescribed in the elderly, the treatment of behavioral and psychological symptoms of dementia remains a difficult problem, considering the lack of a real alternative to these medications. Anticonvulsant mood stabilizers are an interesting solution but none of them, other than carbamazepine, which did, but which is not better tolerated than the usual drugs in this population - was able to prove its efficacy in this indication. Among these medications, valproic acid, gabapentin and lamotrigine should be studied further, and the neuroprotective effect of some of them is an interesting route for research.

Topics: Aged; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Dementia; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Oxcarbazepine; Psychomotor Agitation; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Frontotemporal dementia (FTD) is an insidious presenile neurodegenerative disorder presenting with personality changes, compulsive behaviors, psychosis, apathetic, aberrant, and elated mood and behavior. No psychopharmacologic strategy has proven to be efficacious in the treatment of FTD yet. This is a case report of FTD in a 53-year-old male engineer whose alcohol abuse, but not other compulsive behaviors, responded to topiramate. Alcohol exerts reinforcing effects on cortico-mesolimbic dopamine pathways through the disinhibition of the inhibitory effects of gamma-amino-butyric acid-A neurons in the ventral tegmental area. Topiramate is a sulfamate-substituted fructopyranose derivative that may antagonize the reinforcing effects associated with the abuse liability of alcohol by modulation of cortico-mesolimbic dopamine function. On the basis of the mechanism of action of topiramate, we discuss the possible specificity of action of topiramate to control abusive drinking, but not to treat other clinical symptoms of FTD.

Topics: Alcoholism; Anticonvulsants; Cerebral Cortex; Compulsive Behavior; Dementia; Diagnostic Imaging; Dopamine; Dose-Response Relationship, Drug; Follow-Up Studies; Fructose; Humans; Limbic System; Male; Mental Status Schedule; Middle Aged; Neural Pathways; Topiramate