Use of Topiramate in the Spectrum of Addictive and Eating Disorders: A Systematic Review Comparing Treatment Schemes, Efficacy, and Safety Features.

BACKGROUND AND OBJECTIVE: Topiramate has been approved by the US Food and Drug Administration for the treatment of epilepsy since the 1990s, and it has also been used off-label in the treatment of many types of addictive disorders. To date, no systematic review has embraced the entire field of addiction, both substance use and behavioral addictions, including eating disorders, to compare topiramate-based protocols and the related level of evidence in each addictive disorder. Our objective is to fill this gap. METHODS: A systematic search was conducted using the MEDLINE, PsycINFO, and Cochrane databases without a date or language limit. All trials and meta-analyses assessing the efficacy of topiramate in alcohol use disorder; cocaine use disorder; methamphetamine, nicotine, cannabis, opiate, and benzodiazepine use disorders; binge eating disorder; bulimia; and pathological gambling were analyzed. The quality of the studies was rated using the Cochrane Risk-of-Bias tool for randomized trials (ROB-2), the Risk of Bias In Nonrandomized Studies (ROBINS-I), or the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, depending on the study design. Safety features were assessed based on a wider non-systematic review. RESULTS: Sixty-two articles were reviewed. Treatment protocols were relatively homogenous across addictive disorders, with slow dose titration schemes and a maximum dose range of 200-400 mg per day. The most supportive evidence for topiramate efficacy was found in alcohol use disorder for drinking reduction parameters only. To a lesser extent, topiramate could be a promising therapeutic option for binge eating disorder and cocaine use disorder. Evidence was weak for other addictive disorders. No major tolerability issues were found, provided that basic safety rules were followed. Adverse drug reactions could lead to early treatment discontinuation. DISCUSSION: Though off-label, addiction specialists should consider topiramate as a second-line option for drinking reduction in alcohol use disorder, as well as for binge eating disorder or cocaine use disorder.

The investigation of the effects of topiramate on the hypothalamic levels of fat mass/obesity-associated protein and neuropeptide Y in obese female rats.

OBJECTIVE: The aim of the present study is to investigate the effects of topiramate on the fat mass/obesity-associated protein (FTO) and on the neuropeptide Y (NPY) level in the hypothalamus depending on the recently increased prevalence of obesity. METHOD: In this study, twenty-four female rats were divided into four equal groups: Non-obese control, obese control, non-obese topiramate, and obese topiramate. Obese groups were fed with a 40% high-fat diet. At the end of the 9th week, the drug treatment started and the subjects were treated with topiramate once a day for 6 weeks. All animals underwent cardiac perfusion under high-dose anesthesia on the 15th week. Tissues were analyzed using biochemical, histological, and stereological methods. RESULTS: In terms of neuron number in the arcuate nucleus area, a significant difference was observed among all groups (P < 0.01). The neuron number of the non-obese topiramate group was found to be significantly higher than that of the non-obese control group (P < 0.01). In the examination of the ventromedial nucleus of the entire group, it was observed that the neuron number of the non-obese control group was significantly lower than those of the other groups (P < 0.01). A significant increase in the NPY levels of the obese groups compared to the groups treated with topiramate was observed. Furthermore, the amount of the FTO protein increased in obese rats, while FTO and NPY levels decreased in the groups treated with topiramate. DISCUSSION: In conclusion, the mechanism of the effect of topiramate to create a state of obesity is thought to involve the decrease in the levels of NPY and FTO.

Hipertensión endocraneana idiopática: respuesta al tratamiento Topiramato vs Acetazolamida / Endocranial idiopathic hypertension: response to treatment Topiramate vs. Acetazolamide

INTRODUCCIÓN: El término pseudotumorcerebri se reserva para denominar aquellas hipertensiones endocraneanas (HE) que clínicamente asemejan la existencia de un tumor cerebral, debido a la alteración de la circulación del líquido cefalorraquídeo (LCR). Para su diagnóstico se describen los criterios de Dandy-Smith. OBJETIVOS: Objetivo Primario: Determinar el beneficio del uso de Azetazolamida (ACZ) o Topiramato (TPM) en el tratamiento de la hipertensión endocraneana idiopática. Objetivos Secundarios: Uso de Presión de apertura como parámetro indicador para uso de ACZ o TPM. MATERIALES Y MÉTODOS: Tipo de estudio: Descriptivo Retrospectivo Observacional. RESULTADOS: La media de seguimiento fue de 11 meses, con un rango entre 6-12 meses Se estudiaron 5 pacientes con diagnóstico de Hipertensión Endocraneana Idiopática. Del total de los pacientes 5 (100%) tenían F.O patológico y como síntoma cardinal cefalea, 2 (40%) además vómitos. 3 (60%) fue tratado con Topiramato (TPM) mientras que 2 (40%) recibió acetazolamida (ACZ), ambos sin complicaciones (p= 0,07) Del total de los pacientes 3(60%) presento presión de apertura menor de 40 mmHg mientras que en los restantes 2 (40%) fue mayor a 40 mmHg. De estos últimos el 1 paciente recibió TPM y 1 paciente ACZ. Dos pacientes (40%) presentaron en el seguimiento una recaída sintomática, al intentar descender la medicación. No se pudo definir como parámetro de decisión la presión de apertura en del uso de uno u otro medicamento ya que al evaluar el uso de TPM y ACZ en pacientes con presión de apertura mayor a 41 mmHg solo se detallaron 2 pacientes cada uno tratado con un medicamento de los anteriormente descriptos. (Chi cuadrado p= 0.44). Ninguno de los pacientes tratados requirió otro tratamiento complementario como PL seriadas o válvula de derivación ventrículo peritoneal. CONCLUSION: No se logró determinar beneficio en el uso de un medicamento sobre otro en el tratamiento de la hipertensión endocraneana idiopática (p=0,07), pese al tamaño muestral, el cual podría ser un limitante. Coincidentemente con la literatura sigue sin haber evidencia suficiente. No existe un algoritmo de consenso en cuanto al correcto manejo terapéutico y farmacológico de esta entidad. El uso de TPM o ACZ no condiciona la posterior aparición de complicaciones (p= 0.45) El estudio oftalmológico es esencial para diagnóstico y seguimiento. No se pudo establecer correlación entre el valor obtenido en la medición de la presión de apertura y el tratamiento instaurado. (AU)

INTRODUCTION: The term Pseudotumor cerebri is reserved for those endocranial hypertensio (EH) that resemble clinically the existence of a brain tumor, due to alteration of the circulation of the cerebrospinal fluid (CSF). Classically, the Dandy-Smith criteria for diagnosis are described. TYPE OF STUDY: Descriptive observational. OBJECTIVE: Primary Objective: To determine the benefit of the use of Azetazolamide (ACZ) or Topiramate (TPM) in the treatment of idiopathic endocranial hypertension Secondary Objectives: Use of Opening Pressure as indicator parameter for use of ACZ or TPM. MATERIALS AND METHODS: Observed patients(N:5) per clinic with diagnosis of EIH by criteria of Dandy-Smith in the period 2013-2017. I was performed in all patients: RMNC s/contrast Fundus oculi Lumbar puncture + opening pressure. RESULTS: Of the total of patients (5) 100% had F.O pathological and as cardinal symptom headache, and 40% also vomiting. The mean follow-up was 11 months 60% of the patients was treated with topiramate (TPM) while 40% received acetazolamide (ACZ), both without complications. Of the total of patients 60% presented less than 40 opening pressure mmHg, while that in the remaining 40% was greater than 40 mmHg, of which 50% received TPM and 50% ACZ. 40% presented in tracking a symptomatic relapse, trying to get off the medication. None of the treated patients required other adjunctive therapy such as serial PL or ventricleperitoneal shunt. CONCLUSIONS: It was not possible to determine benefit in the use of one drug over another in the treatment of idiopathic intracranial hypertension (p = 0.07), despite the sample size, which could be a limitation. Coincidentally with the literature there is still not enough evidence. There is no consensus algorithm regarding the correct therapeutic and pharmacological management of this entity. The use of TPM or ACZ does not condition the subsequent appearance of complications (p = 0.45) The ophthalmological study is essential for diagnosis and follow-up. No correlation could be established between the value obtained in the measurement of the opening ression and the treatment established. (AU)