topiramate and Peripheral-Nervous-System-Diseases

Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet Therapy; Disease Progression; Dyslipidemias; Exercise; Humans; Hypoglycemic Agents; Metabolic Syndrome; Obesity; Peripheral Nervous System Diseases; Prediabetic State; Risk Factors; Small Fiber Neuropathy; Topiramate

Antiepileptic drugs are an effective treatment for various forms of neuropathic pain of peripheral origin, although they rarely provide complete pain relief. Multiple multicentre randomised controlled trials have shown clear efficacy of gabapentin and pregabalin for postherpetic neuralgia and painful diabetic neuropathy. Theses drugs can be rapidly titrated and are well tolerated. Topiramate, lamotrigine, carbamazepine and oxcarbazepine are alternatives for the treatment of painful diabetic neuropathy, but should be titrated slowly. Carbamazepine remains the drug of choice for trigeminal neuralgia; however, oxcarbazepine and lamotrigine are potential alternatives. There is an apparent need for large-scale randomised controlled trials on the efficacy of antiepileptic drugs in neuropathic pain in general, and in cancer-related neuropathic pain and neuropathic pain of central origin in particular. Trials with long-term follow-up are required to establish the long-term efficacy of antiepileptic drugs in neuropathic pain. There is only limited scientific evidence to support the idea that drug combinations are likely to be more efficacious and safer than each drug alone; further studies are warranted in this area.

Topics: Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Neuralgia; Oxcarbazepine; Peripheral Nervous System Diseases; Topiramate; Treatment Outcome; Triazines

Oxcarbazepine, topiramate, zonisamide, and levetiracetam are the antiepileptic drugs (AEDs) most recently approved by the US Food and Drug Administration. Based on the experience with carbamazepine, gabapentin, and lamotrigine, these newer AEDs are being investigated for the management of neuropathic pain.. This article reviews preclinical and clinical data on the efficacy and tolerability of these 4 AEDs in the management of neuropathic pain, as well as the pharmacokinetics, drug-interaction potential, adverse effects, and dosing of these agents, with an emphasis on their use in older individuals.. Relevant studies were identified through a MEDLINE search of the Englidh-language literature published between 1986 and May 2003, a review of the reference lists of identified articles, and abstracts from the annual meetings of the American Academy of Neurology (1986-2002) and the 2003 Annual Meeting of the American Pain Society. Search terms were oxcarbazepine, topiramate, zonisamide, and levetiracetam.. Oxcarbazepine and topiramate have been effective in animal models of neuropathic pain. Thirty-four publications on the efficacy and tolerability of the 4 agents were identified (25 case reports/case series, 6 randomized parallel-group studies, and 3 randomized crossover studies). The 9 randomized studies were restricted to oxcarbazepine and topiramate, and 23 (68%) publications were available in abstract form only. These preliminary data suggest that the 4 newer AEDs may be useful in a wide variety of neuropathic pain syndromes; however, additional data, including full-length peer-reviewed reports, are necessary before their true analgesic potential in neuropathic pain can be determined. All 4 agents have pharmacodynamic interactions with other psychotherapeutic drugs, potentiating adverse central nervous system events such as sedation. With the exception of levetiracetam, these drugs also have pharmacokinetic interactions with other drugs, although to a somewhat lesser extent than carbamazepine. These agents have some unique adverse effects not frequently monitored by clinicians, such as hyponatremia, nephrolithiasis, acute myopia with secondary angle-closure glaucoma, and weight loss.. Based on preliminary data, oxcarbazepine, topiramate, zonisamide, and levetiracetam may be useful in the treatment of a wide variety of neuropathic pain syndromes, although full publication of the results of controlled trials is awaited. These agents are associated with specific adverse effects not commonly monitored by clinicians. Of the 4, levetiracetam appears to be easiest to use (ie, no need for dose adjustment in organ dysfunction, no need for laboratory monitoring) and best tolerated, and has not been associated with the unique toxicities seen with oxcarbazepine, topiramate, and zonisamide. The ultimate role of these agents in the therapeutic armamentarium against pain requires further research and experience. In the interim, these 4 agents should be used to treat neuropathic pain in the elderly only when carbamazepine, gabapentin, or lamotrigine cannot be used or when the response to the aforementioned agents is suboptimal.

Topics: Aged; Analgesics, Non-Narcotic; Animals; Carbamazepine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Fructose; Humans; Isoxazoles; Levetiracetam; Oxcarbazepine; Pain; Peripheral Nervous System Diseases; Piracetam; Topiramate; Zonisamide

Oxaliplatin is a cornerstone chemotherapeutic used in the treatment of colorectal cancer, the third leading cause of death in Western countries. Most side effects of this platinum-containing drug are adequately managed in the clinic, although acute and long-term neurotoxicity still severely compromises the quality of life of patients treated with oxaliplatin. We have previously demonstrated that therapeutically relevant concentrations/doses of oxaliplatin lead to a reduction in intracellular pH in mouse dorsal root ganglion (DRG) neurons in vitro and in vivo and that this alteration sensitizes TRPA1 and TRPV1 channels, which most likely mediate the allodynia associated with treatment. In this study, we show that oxaliplatin leads to a reduction of intracellular pH by forming adducts with neuronal haemoglobin, which acts in this setting as a proton buffer. Furthermore, we show that FDA-approved drugs that inhibit carbonic anhydrase (an enzyme that is linked to haemoglobin in intracellular pH homeostasis), ie, topiramate and acetazolamide, revert (1) oxaliplatin-induced cytosolic acidification and TRPA1 and TRPV1 modulation in DRG neurons in culture, (2) oxaliplatin-induced cytosolic acidification of DRG of treated animals, and (3) oxaliplatin-induced acute cold allodynia in mice while not affecting OHP-induced cytotoxicity on cancer cells. Our data would therefore suggest that reversal of oxaliplatin-induced cytosolic acidification is a viable strategy to minimize acute oxaliplatin-induced symptoms.

Topics: Acetazolamide; Animals; Antineoplastic Agents; Buffers; Carbonic Anhydrase Inhibitors; Ganglia, Spinal; HEK293 Cells; Hemoglobins; Humans; Hydrogen-Ion Concentration; Hyperalgesia; Mice; Mice, Inbred BALB C; Neurons; Oxaliplatin; Peripheral Nervous System Diseases; Primary Cell Culture; Protons; Topiramate; Transient Receptor Potential Channels

Oxaliplatin (OHP) Induced Peripheral Neurotoxicity (OIPN) is one of the dose-limiting toxicities of the drug and these adverse effects limit cancer therapy with L-OHP, used for colorectal cancer treatment. Acute neurotoxicity consists of symptoms that are the hallmarks of a transient axonal hyperexcitability; chronic neurotoxicity has a clinical picture compatible with a length-dependent sensory neuropathy. Acute OIPN pathogenesis has been linked to sodium voltage-operated channels (Na + VOC) dysfunction and it has been advocated as a possible predisposing factor to chronic neurotoxicity. We tested if topiramate (TPM), a well-known Na + VOC modulator, was able to modify acute as well as chronic OIPN. The project was divided into two parts. In Experiment 1 we tested by means of Nerve Excitability Testing (NET) a cohort of female Wistar rats to assess TPM effects after a single OHP administration (5 mg/kg, iv). In Experiment 2 we assessed TPM effects after chronic OHP treatment (5 mg/kg, 2qw4ws, iv) using NET, nerve conduction studies (NCS), behavioral tests and neuropathology (caudal nerve morphometry and morphology and Intraepidermal Nerve Fiber [IENF] density). In Experiment 1 TPM was able to prevent OHP effects on Na + VOC: OHP treatment induced a highly significant reduction of the sensory nerve's threshold, during the superexcitability period (p-value = 0.008), whereas TPM co-administration prevented this effect. In Experiment 2 we verified that TPM was able to prevent not only acute phenomena, but also to completely prevent chronic OIPN. This latter observation was supported by a multimodal approach: in fact, only OHP group showed altered findings compared to CTRL group at a neurophysiological (proximal caudal nerve sensory nerve action potential [SNAP] amplitude, p-value = 0.001; distal caudal nerve SNAP amplitude, p-value<0.001, distal caudal nerve sensory conduction velocity, p-value = 0.04), behavioral (mechanical threshold, p-value 0.003) and neuropathological levels (caudal nerve fibers density, p-value 0.001; IENF density, p-value <0.001). Our data show that TPM is a promising drug to prevent both acute and chronic OIPN. These findings have a high translational potential, since they were obtained using outcome measures that match clinical practice and TPM is already approved for clinical use being free from detrimental interaction with OHP anticancer properties.

Topics: Animals; Antineoplastic Agents; Axons; Female; Neural Conduction; Neuroprotective Agents; Neurotoxicity Syndromes; Oxaliplatin; Pain Measurement; Peripheral Nervous System Diseases; Rats; Rats, Wistar; Topiramate

Additional medications are needed for inflammatory bowel disease (IBD) as existing therapies are incompletely effective and can be costly and toxic. Preclinical studies suggest that topiramate (an anticonvulsant) may have disease-modifying properties in IBD, but its efficacy in humans is unknown.. To evaluate whether topiramate use is associated with clinical benefit in IBD patients.. We conducted a retrospective cohort study using administrative claims data from the MarketScan databases. Persons with IBD were identified between 2000 and 2010. New users of topiramate were compared with users of other anticonvulsant and anti-migraine medications. The primary outcome was a new prescription for an oral steroid (≥14 days). Secondary outcomes included initiation of biologic agents, abdominal surgery, and hospitalization. Cox proportional hazard modeling was used to adjust for potential confounders.. We identified 773 new users of topiramate and 958 users of comparator drugs. After adjusting for potential confounders, topiramate use was not associated with the primary outcome of steroid prescriptions [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 0.74, 1.73]. Results did not differ significantly by IBD subtype. There was no difference between topiramate users and users of comparator drugs with respect to post-exposure initiation of biologic agents (HR 0.93, 95 % CI 0.39, 2.19), abdominal surgery (HR 1.04, 95 % CI 0.17, 6.41), or hospitalization (HR 0.86, 95 % CI 0.62, 1.19).. In this large U.S. administrative claims study, topiramate use was not associated with markers of IBD flares. These results cast doubt on whether topiramate may be an effective adjunct to current IBD therapy.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Child; Child, Preschool; Databases, Factual; Female; Follow-Up Studies; Fructose; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Male; Middle Aged; Migraine Disorders; Peripheral Nervous System Diseases; Pharmacoepidemiology; Proportional Hazards Models; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Young Adult

We aimed to compare the effects of antiepileptic drugs and provide findings of peripheral nerve impairment using standard electrophysiological techniques.. Young adult outpatients with epilepsy on monotherapy for no less than 6 months with carbamazepine (CBZ), valproic acid (VPA), oxcarbazepine (OXC) and topiramate (TPM) were examined. Patients who had any other disease that could effect nerve conduction studies and who had neuropathic symptoms were excluded.. Each group contained 15 patients and 20 healthy subjects were examined as the control group. Prolonged latency of median sensory nerve (P = 0.004), ulnar sensory nerve (P = 0.01) and sural nerve (P = 0.003) with a diminished nerve conduction velocity was observed in the CBZ group (P = 0.014, P = 0.002, P = 0.025, respectively). No correlation was found between VPA, OXC and TPM and the nerve conduction studies (P > 0.05).. Valproic acid, oxcarbazepine and topiramate don't have effects on nerve conduction studies. Mild electrophysiological changes contribute to carbamazepine therapy.

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Female; Fructose; Humans; Male; Median Nerve; Neural Conduction; Oxcarbazepine; Peripheral Nerves; Peripheral Nervous System Diseases; Severity of Illness Index; Sural Nerve; Topiramate; Ulnar Nerve; Valproic Acid; Young Adult

Topics: Adolescent; Back Pain; Diagnosis, Differential; Fructose; Humans; Magnetic Resonance Imaging; Male; Neuroprotective Agents; Paresthesia; Peripheral Nervous System Diseases; Thoracic Nerves; Topiramate

Venlafaxine (Effexor; Wyeth Lederle), a serotoninergic-like anti-depressant, and Topiramate (Epitomax; Jansen Cilag), a new anti-epileptic drug, share some evidence of clinical activity in the treatment of neuropathic pain. Several anti-cancer agents have neurosensory toxicity as limiting toxicity of their repeated administration. One of the most recent and the most widely used is oxaliplatin. No medication is presently known to be active against oxaliplatin permanent neurosensory toxicity. We observed that venlafaxine hydrochloride or low-dose topiramate could be active against the permanent neuropathy-related symptoms of oxaliplatin. Both agents allowed pain relief and a significant autonomy improvement. These preliminary results invite us to evaluate further venlafaxine hydrochloride and topiramate for the treatment of permanent anti-cancer chemotherapy-induced neuropathies.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Cyclohexanols; Female; Fructose; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Paresthesia; Peripheral Nervous System Diseases; Recovery of Function; Topiramate; Venlafaxine Hydrochloride

Topics: Acetaminophen; Acetates; Amines; Analgesics; Animals; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Delivery Systems; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Nitrates; Pain; Peripheral Nervous System Diseases; Piracetam; Pregabalin; Topiramate