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1.
Cochrane Database Syst Rev ; 1: CD001415, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33434292

RESUMEN

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. MAIN RESULTS: We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs. AUTHORS' CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsias Parciales/tratamiento farmacológico , Gabapentina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Quimioterapia Combinada/métodos , Gabapentina/administración & dosificación , Gabapentina/efectos adversos , Humanos , Análisis de Intención de Tratar , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Ann Intern Med ; 173(2): JC5, 2020 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-32687757

RESUMEN

SOURCE CITATION: Anton RF, Latham P, Voronin K, et al. Efficacy of gabapentin for the treatment of alcohol use disorder in patients with alcohol withdrawal symptoms: a randomized clinical trial. JAMA Intern Med. 2020;180:1-9. 32150232.


Asunto(s)
Alcoholismo , Síndrome de Abstinencia a Sustancias , Consumo de Bebidas Alcohólicas , Alcoholismo/complicaciones , Alcoholismo/tratamiento farmacológico , Gabapentina/uso terapéutico , Humanos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico
3.
Lancet Neurol ; 19(3): 226-233, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32085836

RESUMEN

BACKGROUND: S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. METHODS: RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18-85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7-20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0-1 versus 2-6 and 0-2 versus 3-6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615. FINDINGS: Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64-1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81-1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0-2 vs 3-6 or mRS 0-1 vs 2-6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2-8] in 150 mg S44819 group, 4 [2-7] in 300 mg S44819 group, and 4 [2-6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0-26·0] in 150 mg S44819 group, 23·0 [19·0-26·5] in 300 mg S44819 group, and 22·0 [17·0-26·0] in placebo group), time needed to complete parts A (50 s [IQR 42-68] in 150 mg S44819 group, 49 s [36-63] in 300 mg S44819 group, and 50 s [38-68] in placebo group) and B (107 s [81-144] in 150 mg S44819 group, 121 s [76-159] in 300 mg S44819 group, and 130 s [86-175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60-100] in 150 mg S44819 group, 90 [70-100] in 300 mg S44819 group, and 90 [70-100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. INTERPRETATION: There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. FUNDING: Servier.


Asunto(s)
Benzodiazepinas/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Oxazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/efectos de los fármacos , Isquemia Encefálica/complicaciones , Método Doble Ciego , Femenino , Antagonistas del GABA/uso terapéutico , Antagonistas de Receptores de GABA-A/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , Ácido gamma-Aminobutírico/uso terapéutico
4.
Cochrane Database Syst Rev ; 1: CD006282, 2020 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-32006461

RESUMEN

BACKGROUND: Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a (point) mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. This is an update of a review first published in 2009 and previously updated in 2011. OBJECTIVES: To evaluate if drug treatment is able to slow or arrest the disease progression of SMA types II and III, and to assess if such therapy can be given safely. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. In October 2018, we also searched two trials registries to identify unpublished trials. SELECTION CRITERIA: We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a homozygous deletion or hemizygous deletion in combination with a point mutation in the second allele of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis. The primary outcome measure was change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full-time ventilation and adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1-replacement with viral vectors are out of the scope of this review, but a summary is given in Appendix 1. Drug treatment for SMA type I is the topic of a separate Cochrane Review. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: The review authors found 10 randomised, placebo-controlled trials of treatments for SMA types II and III for inclusion in this review, with 717 participants. We added four of the trials at this update. The trials investigated creatine (55 participants), gabapentin (84 participants), hydroxyurea (57 participants), nusinersen (126 participants), olesoxime (165 participants), phenylbutyrate (107 participants), somatotropin (20 participants), thyrotropin-releasing hormone (TRH) (nine participants), valproic acid (33 participants), and combination therapy with valproic acid and acetyl-L-carnitine (ALC) (61 participants). Treatment duration was from three to 24 months. None of the studies investigated the same treatment and none was completely free of bias. All studies had adequate blinding, sequence generation and reporting of primary outcomes. Based on moderate-certainty evidence, intrathecal nusinersen improved motor function (disability) in children with SMA type II, with a 3.7-point improvement in the nusinersen group on the Hammersmith Functional Motor Scale Expanded (HFMSE; range of possible scores 0 to 66), compared to a 1.9-point decline on the HFMSE in the sham procedure group (P < 0.01; n = 126). On all motor function scales used, higher scores indicate better function. Based on moderate-certainty evidence from two studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: creatine (median change 1 higher, 95% confidence interval (CI) -1 to 2; on the Gross Motor Function Measure (GMFM), scale 0 to 264; n = 40); and combination therapy with valproic acid and carnitine (mean difference (MD) 0.64, 95% CI -1.1 to 2.38; on the Modified Hammersmith Functional Motor Scale (MHFMS), scale 0 to 40; n = 61). Based on low-certainty evidence from other single studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: gabapentin (median change 0 in the gabapentin group and -2 in the placebo group on the SMA Functional Rating Scale (SMAFRS), scale 0 to 50; n = 66); hydroxyurea (MD -1.88, 95% CI -3.89 to 0.13 on the GMFM, scale 0 to 264; n = 57), phenylbutyrate (MD -0.13, 95% CI -0.84 to 0.58 on the Hammersmith Functional Motor Scale (HFMS) scale 0 to 40; n = 90) and monotherapy of valproic acid (MD 0.06, 95% CI -1.32 to 1.44 on SMAFRS, scale 0 to 50; n = 31). Very low-certainty evidence suggested that the following interventions had little or no effect on motor function: olesoxime (MD 2, 95% -0.25 to 4.25 on the Motor Function Measure (MFM) D1 + D2, scale 0 to 75; n = 160) and somatotropin (median change at 3 months 0.25 higher, 95% CI -1 to 2.5 on the HFMSE, scale 0 to 66; n = 19). One small TRH trial did not report effects on motor function and the certainty of evidence for other outcomes from this trial were low or very low. Results of nine completed trials investigating 4-aminopyridine, acetyl-L-carnitine, CK-2127107, hydroxyurea, pyridostigmine, riluzole, RO6885247/RG7800, salbutamol and valproic acid were awaited and not available for analysis at the time of writing. Various trials and studies investigating treatment strategies other than nusinersen (e.g. SMN2-augmentation by small molecules), are currently ongoing. AUTHORS' CONCLUSIONS: Nusinersen improves motor function in SMA type II, based on moderate-certainty evidence. Creatine, gabapentin, hydroxyurea, phenylbutyrate, valproic acid and the combination of valproic acid and ALC probably have no clinically important effect on motor function in SMA types II or III (or both) based on low-certainty evidence, and olesoxime and somatropin may also have little to no clinically important effect but evidence was of very low-certainty. One trial of TRH did not measure motor function.


Asunto(s)
Fármacos Neuroprotectores/uso terapéutico , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Adolescente , Aminas/uso terapéutico , Niño , Preescolar , Creatina/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Humanos , Hidroxiurea/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Hormona Liberadora de Tirotropina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico
5.
Artículo en Ruso | MEDLINE | ID: mdl-31793540

RESUMEN

AIM: To evaluate the efficacy and safety of hopantenic acid (Pantogam) in the complex treatment of prematurely born infants, aged 6-12 months, with psychomotor developmental delay due to hypoxic-ischemic encephalopathy. MATERIAL AND METHODS: Eighty-seven patients were randomized into two groups: 44 received standardized treatment and pantogam for two months, 43 standardized treatment and placebo. Pantogam (syrup 100 mg/ml) or placebo were prescribed orally 15-30 minutes after feeding, twice a day, in a daily dosage of 30-50 mg/kg body weight. The assessment of psychomotor development from birth to two years was performed with the Griffiths Mental Development Scales (GMDS-ER) twice (before and after completion of therapy). RESULTS: The response to two month therapy determined as the reduction of developmental delay for more than 6% of the initial GMDS-ER general quotient (GQ) score was significantly better in the group I after pantogam treatment (63.6% of patients) compared to group II (36.4%, p=0.021). Group I demonstrated the significant decrease of the developmental delay in two domains ('Personal-Social' and 'Performance') and a trend to overcome the delay in three other domains: 'Locomotor', 'Hearing and Speech', 'Eye and Hand Coordination'. The improvement after pantogam treatment was more obvious in the subgroup of infants born late preterm (gestational age 34-36 weeks) compared to infants born moderate preterm (gestational age 32-33 weeks). The favorable safety profile of pantogam was confirmed, comparable to that of placebo. CONCLUSION: Pantogam is efficient and safe medication in the complex treatment of psychomotor developmental delay in preterm infants, aged 6-12 months.


Asunto(s)
Hipoxia-Isquemia Encefálica , Recien Nacido Prematuro , Nootrópicos , Ácido Pantoténico/análogos & derivados , Ácido gamma-Aminobutírico/análogos & derivados , Niño , Desarrollo Infantil , Discapacidades del Desarrollo , Método Doble Ciego , Femenino , Edad Gestacional , Humanos , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Lactante , Recién Nacido , Nootrópicos/uso terapéutico , Ácido Pantoténico/uso terapéutico , Embarazo , Desempeño Psicomotor , Ácido gamma-Aminobutírico/uso terapéutico
6.
Oxid Med Cell Longev ; 2019: 4028394, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31814874

RESUMEN

Ischemia-reperfusion (I/R) injury is a common pathological process, which may lead to dysfunctions and failures of multiple organs. A flawless medical way of endogenous therapeutic target can illuminate accurate clinical applications. γ-Aminobutyric acid (GABA) has been known as a marker in I/R injury of the central nervous system (mainly in the brain) for a long time, and it may play a vital role in the occurrence of I/R injury. It has been observed that throughout cerebral I/R, levels, syntheses, releases, metabolisms, receptors, and transmissions of GABA undergo complex pathological variations. Scientists have investigated the GABAergic enhancers for attenuating cerebral I/R injury; however, discussions on existing problems and mechanisms of available drugs were seldom carried out so far. Therefore, this review would summarize the process of pathological variations in the GABA system under cerebral I/R injury and will cover corresponding probable issues and mechanisms in using GABA-related drugs to illuminate the concern about clinical illness for accurately preventing cerebral I/R injury. In addition, the study will summarize the increasing GABA signals that can prevent I/R injuries occurring in peripheral organs, and the roles of GABA were also discussed correspondingly.


Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Sistema Nervioso Central/patología , Humanos , Daño por Reperfusión/patología , Ácido gamma-Aminobutírico/farmacología
7.
J Biomater Sci Polym Ed ; 30(17): 1658-1669, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31402754

RESUMEN

In order to overcome the side effects of pancreatic transplantation and insulin injection treatment for type I diabetes, we established a drug delivery system employing nanoparticle embedded microcapsules (NEMs). The system co-encapsulated chitosan nanoparticles with γ-aminobutyric acid and ß-TC-6 cells for combined drug and cell therapy in diabetes mellitus (DM). The NEMs, which were formed via high-voltage electrostatic method, had an excellent sphericity with a smooth surface. The average size NEM was 245.52 ± 22.00 µm, which indicated a good size for cell encapsulation. Haemolysis rate of NEMs at concentrations of 100, 200 or 300 mg/mL were all below 5%. Relative viability rates of L929 cells with the same concentrations at 24, 48 or 72 h were all above 80%. We implanted bioactive NEMs into type 1 DM mice to evaluate the effect of the combined therapy. The level of blood glucose in the group receiving the combined therapy decreased during the first 2 weeks of treatment. During the next week, the level of blood glucose stayed in a safe range. Body weight continuously increased during the postoperative period after combined therapy group. Oral glucose tolerance test (OGTT) performed after 24 d showed that the level of blood glucose combined therapy reached the maximum peak of 13.04 mmol/L, lower than 16.56 mmol/L for the cell therapy group. This primary study indicated that microencapsulation technology and combined therapy are promising for the treatment of type I diabetes mellitus.


Asunto(s)
Quitosano/química , Diabetes Mellitus Tipo 1/terapia , GABAérgicos/administración & dosificación , Células Secretoras de Insulina/trasplante , Nanopartículas/química , Ácido gamma-Aminobutírico/administración & dosificación , Animales , Glucemia/análisis , Cápsulas , Línea Celular , Células Inmovilizadas/citología , Células Inmovilizadas/trasplante , Diabetes Mellitus Tipo 1/sangre , GABAérgicos/uso terapéutico , Células Secretoras de Insulina/citología , Ratones , Ácido gamma-Aminobutírico/uso terapéutico
8.
Molecules ; 24(15)2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31344785

RESUMEN

Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.


Asunto(s)
Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacología , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Neurotransmisores/metabolismo , Ácido gamma-Aminobutírico/uso terapéutico
9.
Eur J Pharmacol ; 858: 172475, 2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31228456

RESUMEN

The development of effective therapeutics for cancer-induced bone pain (CIBP) remains a tremendous challenge owing to its unclear mechanisms. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). Emerging studies have shown that disinhibition in the spinal cord dorsal horn may account for the development of chronic pain. However, the role of GABA in the development of CIBP remains elusive. In addition, accumulating evidence has shown that neuroglial cells in the peripheral nervous system, especially astrocytes and microglial cells, played an important role in the maintenance of CIBP. In this study, we investigated the expression of GABA and Gamma-aminobutyric acid transporter-1 (GAT-1), a transporter of GABA. Our results demonstrate that GABA was decreased in CIBP rats as expected. However, the expression of glutamic acid decarboxylase (GAD) 65 was up-regulated on day 21 after surgery, while the expression of GAD 67 remained unchanged after surgery. We also found that the expression of GAT-1 was up-regulated mainly in the astrocytes of the spinal cord. Moreover, we evaluated the analgesic effect of exogenous GABA and the GAT-1 inhibitor. Intrathecal administration of exogenous GABA and NO-711 (a GAT-1 selective inhibitor) significantly reversed CIBP-induced mechanical allodynia in a dose-dependent manner. These results firstly show that neuron-glia interactions, especially on the GABAergic pathway, contribute to the development of CIBP. In conclusion, exogenous GABA and GAT-1 inhibitor might be alternative therapeutic strategies for the treatment of CIBP.


Asunto(s)
Neoplasias Óseas/complicaciones , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/patología , Comunicación Celular/efectos de los fármacos , Neuroglía/patología , Neuronas/patología , Ácido gamma-Aminobutírico/farmacología , Animales , Neoplasias Óseas/secundario , Dolor en Cáncer/etiología , Línea Celular Tumoral , Femenino , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glutamato Descarboxilasa/metabolismo , Hiperalgesia/tratamiento farmacológico , Neuroglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/uso terapéutico
10.
Contemp Clin Trials ; 82: 93-100, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31229619

RESUMEN

BACKGROUND: Evidence suggests that GABA may reduce pancreatic inflammation, protect ß-cells from autoimmune destruction, and potentiate the regeneration of new ß-cells in the setting of type 1 diabetes mellitus (T1DM). The enzyme GAD, also expressed in human pancreatic ß-cells, is an antigenic target of reactive T cells. We hypothesized that treatment of children with recent onset T1DM with GABA or combination GABA with GAD will preserve ß-cell function and ameliorate autoimmune dysregulation. METHODS: This is a one-year, prospective, randomized, double-blind, placebo-controlled trial. Ninety-nine patients aged 4-18 years with newly diagnosed T1DM are randomized into three treatment groups: 1) oral GABA twice daily in addition to two injections of recombinant GAD enzyme, 2) oral GABA plus placebo GAD injections, or 3) placebo GABA and placebo GAD. Patients are evaluated at baseline and months 1, 5, 8 and 12. Mixed meal tolerance testing is performed at all but the 8-month visit. Laboratory studies will assess indices of beta and alpha cell function, glycemic control, immunophenotyping, and diabetes-related autoantibodies. RESULTS: The primary outcome is the effect on pancreatic ß-cell function as measured by meal-stimulated c-peptide secretion compared between the treatment groups before and after one year of treatment. Secondary outcomes include: 1) fasting and meal stimulated glucagon and proinsulin levels, 2) response in insulin usage by participants, 3) indices of immune cell function, and 4) effect on autoantibodies GAD65, ICA512, and ZnT8. CONCLUSIONS: This trial will determine the safety and efficacy of GABA and combination GABA/GAD therapy to delay T1DM progression in children.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glutamato Descarboxilasa/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glutamato Descarboxilasa/administración & dosificación , Humanos , Inyecciones Subcutáneas , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido gamma-Aminobutírico/administración & dosificación
11.
J Vis Exp ; (147)2019 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-31157762

RESUMEN

Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the cases, serious side effects affect the quality of life of patients. Moreover, a high percentage of epileptic patients are drug resistant; in their case, neurosurgery or neurostimulation are necessary. Therefore, the major goal of epilepsy research is to discover new therapies which are either capable of curing epilepsy without side effects or preventing recurrent seizures in drug-resistant patients. Neuroengineering provides new approaches by using novel strategies and technologies to find better solutions to cure epileptic patients at risk. As a demonstration of a novel experimental protocol in an acute mouse model of epilepsy, a direct in situ electrophoretic drug delivery system is used. Namely, a neural probe incorporating a microfluidic ion pump (µFIP) for on-demand drug delivery and simultaneous recording of local neural activity is implanted and demonstrated to be capable of controlling 4-aminopyridine-induced (4AP-induced) seizure-like event (SLE) activity. The γ-aminobutyric acid (GABA) concentration is kept in the physiological range by the precise control of GABA delivery to reach an antiepileptic effect in the seizure focus but not to cause overinhibition-induced rebound bursts. The method allows both the detection of pathological activity and intervention to stop seizures by delivering inhibitory neurotransmitters directly to the epileptic focus with precise spatiotemporal control. As a result of the developments to the experimental method, SLEs can be induced in a highly localized manner that allows seizure control by the precisely tuned GABA delivery at the seizure onset.


Asunto(s)
Electroforesis , Epilepsia/tratamiento farmacológico , Convulsiones/prevención & control , Ácido gamma-Aminobutírico/administración & dosificación , Ácido gamma-Aminobutírico/uso terapéutico , 4-Aminopiridina , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Craneotomía , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Microfluídica , Convulsiones/inducido químicamente
13.
Psychiatry Res ; 271: 649-657, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30791338

RESUMEN

The purpose of this study was to investigate the effects and mechanism of repeated oral administration of gamma-aminobutyric acid (GABA) on anxiety-like behaviors induced by emotional stress. Male Sprague-Dawley rats were randomly divided into five groups (8 rats each): control, emotional stress model, three emotional stress + GABA-treated groups (0.5, 1, 2 mg/kg). The rats were given empty water bottles after the training of drinking water to induce emotional stress. Each group was treated with saline or different doses of GABA respectively for 21 consecutive days. Then open field and elevated plus maze were used to assess anxiety-like behaviors. Both frontal cortex and plasma NO metabolites nitrate and nitrite (NOx) levels were determined spectrophotometrically. Results showed that oral administration of GABA significantly reversed the stress-induced anxiety-like negative responses dose-dependently. The frontal cortex NOx levels were lower in stressed rats than in control group (P < 0.05), but higher in 2 mg/kg GABA-treated group than stress model group (P < 0.05). On the other hand, NOx levels in plasma showed a gradual decline trend. Collectively, these results suggest that short repeated oral administration of GABA has an anxiolytic-like effect possibly via preventing NO reduction caused by stress and improving availability of NO in the frontal cortex.


Asunto(s)
Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Estrés Psicológico/complicaciones , Ácido gamma-Aminobutírico/uso terapéutico , Administración Oral , Animales , Ansiolíticos/administración & dosificación , Ansiedad/etiología , Ansiedad/metabolismo , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/metabolismo , Ácido gamma-Aminobutírico/administración & dosificación
14.
J Neurosurg ; 132(1): 239-251, 2019 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-30611141

RESUMEN

OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.


Asunto(s)
Analgesia/métodos , Estimulación Encefálica Profunda , Glicina/fisiología , Corteza Motora/fisiopatología , Neuralgia/terapia , Sustancia Gris Periacueductal/fisiopatología , Ciática/terapia , Ácido gamma-Aminobutírico/fisiología , Animales , Bicuculina/administración & dosificación , Bicuculina/toxicidad , Vías Eferentes/efectos de los fármacos , Vías Eferentes/fisiología , Antagonistas del GABA/administración & dosificación , Antagonistas del GABA/toxicidad , Ácido Glutámico/análisis , Glicina/análisis , Glicina/antagonistas & inhibidores , Glicina/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/fisiopatología , Hiperalgesia/terapia , Masculino , Microdiálisis , Microinyecciones , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Umbral del Dolor , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas , Ratas Wistar , Nervio Ciático/lesiones , Ciática/tratamiento farmacológico , Ciática/fisiopatología , Estricnina/administración & dosificación , Estricnina/toxicidad , Ácido gamma-Aminobutírico/análisis , Ácido gamma-Aminobutírico/uso terapéutico
15.
J Am Geriatr Soc ; 67(6): 1174-1181, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30694557

RESUMEN

BACKGROUND/OBJECTIVES: Peripheral neuropathy is a common diabetes complication that can increase fall risk. Regarding fall risk, the impact of pain management using tricyclic antidepressants (TCAs) or γ-aminobutyric acid (GABA) analogs is unclear because these medications can also cause falls. This study investigates the impact of these drugs on fall and fracture risk in older diabetic peripheral neuropathy (DPN) patients. DESIGN: Historical cohort study with 1-to-1 propensity matching of TCA/GABA-analog users and nonusers. SETTING: Nationally representative 5% Medicare sample between the years 2008 and 2010. PARTICIPANTS: After applying all selection criteria, 5,550 patients with prescription and 22,200 patients without prescription of TCAs/GABA-analogs were identified. Both patient groups were then stratified for fall history and matched based on propensity of receiving TCAs/GABA-analogs within each group. MEASUREMENTS: Patients were followed until the first incidence of fall or the first incidence of fracture during the follow-up period (for up to 5 years). RESULTS: After matching, users and nonusers were largely similar. After covariate adjustment, TCA/GABA-analog use was associated with a statistically significant increase in fall risk (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.03-1.20), but was not associated with fracture risk (adjusted HR = 1.09; 95% CI = 0.99-1.19) in the conventional analysis. Treating TCA/GABA-analog use as a time-dependent covariate resulted in statistically significant associations of TCA/GABA-analog use with both fall and fracture risk (HR = 1.26 [95% CI = 1.17-1.36]; and HR = 1.12 [95% CI = 1.02-1.24], respectively). CONCLUSION: Among older patients with DPN, GABA-analogs or TCAs increase fall risk and possibly fracture risk. Use of these medications is therefore a potentially modifiable risk factor for falls and fractures in this population.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Antidepresivos Tricíclicos/uso terapéutico , Neuropatías Diabéticas , Fracturas Óseas/epidemiología , Ácido gamma-Aminobutírico/uso terapéutico , Anciano , Estudios de Cohortes , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/tratamiento farmacológico , Femenino , Fracturas Óseas/cirugía , Humanos , Incidencia , Masculino , Medicare/estadística & datos numéricos , Inhibidores de la Captación de Serotonina/uso terapéutico , Estados Unidos/epidemiología
16.
Alcohol Clin Exp Res ; 43(1): 158-169, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30403402

RESUMEN

BACKGROUND: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). METHODS: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. RESULTS: The GE-XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications. CONCLUSIONS: Overall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.


Asunto(s)
Alcoholismo/tratamiento farmacológico , Carbamatos/efectos adversos , Carbamatos/uso terapéutico , Preparaciones de Acción Retardada/uso terapéutico , Ácido gamma-Aminobutírico/análogos & derivados , Adulto , Alcoholismo/terapia , Terapia Conductista , Carbamatos/administración & dosificación , Carbamatos/farmacocinética , Terapia Combinada , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Profármacos/uso terapéutico , Terapia Asistida por Computador , Resultado del Tratamiento , Adulto Joven , Ácido gamma-Aminobutírico/administración & dosificación , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/farmacocinética , Ácido gamma-Aminobutírico/uso terapéutico
17.
Zh Nevrol Psikhiatr Im S S Korsakova ; 118(10): 115-121, 2018.
Artículo en Ruso | MEDLINE | ID: mdl-30499507

RESUMEN

Essential arterial hypertension (AH) is one of the main risk factors for the development of cognitive impairment and dementia. Cognitive decline is an early sign of brain damage as a target organ of hypertension, it occurs even in patients with uncomplicated hypertension with minimal duration of disease. Cognitive impairment progresses with increasing age and hypertension duration, as well as in non-controlled AH. In patients with hypertension, the prevalence of emotional disorders - anxiety and depression is also high. In addition to antihypertensive therapy, hypertensive patients need correction of concomitant cognitive and emotional disorders. Rat-gopantenic acid simultaneously corrects both emotional and cognitive impairment, and has a good tolerability profile as well. An analysis of the evidence base of rac-gopantenic acid showed its high efficacy in the treatment of mental disorders and good tolerability along with a positive effect on somatic disorders and results of antihypertensive therapy. Taken together, they enhance adherence to treatment and, consequently, reduce the cardiovascular risk.


Asunto(s)
Trastornos del Conocimiento , Trastorno Depresivo , Hipertensión , Antihipertensivos , Ansiedad/complicaciones , Ansiedad/tratamiento farmacológico , Cognición , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/tratamiento farmacológico , Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Humanos , Hipertensión/complicaciones , Ácido Pantoténico/análogos & derivados , Ácido Pantoténico/uso terapéutico , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico
18.
Cochrane Database Syst Rev ; 10: CD009622, 2018 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-30376593

RESUMEN

BACKGROUND: Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal models of cerebrovascular disease. However, the sedative effects of GABA receptor agonists have limited their wider application in people with acute stroke, due to the potential risk of stupor. This is an update of a Cochrane Review first published in 2013, and previously updated in 2014 and 2016. OBJECTIVES: To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (accessed May 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) 2018, Issue 4 (accessed May 2018), MEDLINE (from 1949 to May 2018), Embase (from 1980 to May 2018), CINAHL (from 1982 to May 2018), AMED (from 1985 to May 2018), and 11 Chinese databases (accessed May 2018). In an effort to identify further published, unpublished, and ongoing trials we searched ongoing trial registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) investigating GABA receptor agonists versus placebo for people with acute stroke (within 12 hours after stroke onset), with the primary outcomes of efficacy and safety. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed the risk of bias. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: We included five trials with 3838 participants (acute ischemic or hemorrhagic stroke patients, 3758 analyzed). Most of the participants recruited had acute ischaemic stroke, with limited data available from participants with other stroke subtypes, including total anterior circulation syndrome (TACS). The methodological quality of the included trials was generally good, with an unclear risk for selection bias only. For death and dependency at three months, pooled results did not find a significant difference for chlormethiazole versus placebo (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.96 to 1.11; four trials; 2909 participants; moderate-quality evidence) and for diazepam versus placebo (RR 0.94, 95% CI 0.82 to 1.07; one trial; 849 participants; moderate-quality evidence). The most frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; 2527 participants; moderate-quality evidence) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46; two trials; 2527 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke. More well-designed RCTs with large samples of participants with total anterior circulation syndrome are required to determine if there are benefits for this subgroup. Somnolence and rhinitis are frequent adverse events related to chlormethiazole.


Asunto(s)
Clormetiazol/uso terapéutico , Diazepam/uso terapéutico , Agonistas del GABA/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Enfermedad Aguda , Clormetiazol/efectos adversos , Diazepam/efectos adversos , Trastornos de Somnolencia Excesiva/inducido químicamente , Agonistas del GABA/efectos adversos , Humanos , Fármacos Neuroprotectores/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis/inducido químicamente , Accidente Cerebrovascular/mortalidad
19.
Cochrane Database Syst Rev ; 10: CD001415, 2018 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-30357813

RESUMEN

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2013.Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially those with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web, 20 March 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 March 2018), ClinicalTrials.gov (20 March 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 20 March 2018). We imposed no language restrictions. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. MAIN RESULTS: We included 12 trials representing 2607 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall RR for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 trials, 1206 participants; moderate-quality evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-quality evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-quality evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-quality evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-quality evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-quality evidence). There were no significant differences for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-quality evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-quality evidence). Overall, the studies were rated at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall quality of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals. AUTHORS' CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsias Parciales/tratamiento farmacológico , Gabapentina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Quimioterapia Combinada/métodos , Gabapentina/administración & dosificación , Gabapentina/efectos adversos , Humanos , Análisis de Intención de Tratar , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Medicine (Baltimore) ; 97(38): e11581, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30235654

RESUMEN

BACKGROUND: The purpose of this meta-analysis from randomized controlled trials (RCTs) was to determine the efficacy and safety of the preoperative use of gabapentin for the treatment of acute and chronic postoperative pain following breast cancer surgery. METHODS: In November 2017, a systematic computer-based search was conducted in PubMed, Embase, Web of Science, Cochrane Library, and Google databases. RCTs comparing gabapentin with placebo in patients undergoing breast cancer surgery were retrieved. The primary endpoint was the visual analog scale (VAS) after surgery and 24 hours after surgery and total morphine consumption. The secondary outcomes were incidence of chronic pain and complications (the incidence of nausea). Software Stata 12.0 was used for meta-analysis. RESULTS: Finally, 9 RCTs were included in the meta-analysis. Results indicated that gabapentin was associated with reduced pain scores after surgery and 24 hours after surgery. Meanwhile, oral gabapentin was associated with a reduction of the total morphine consumption after breast cancer surgery. Similarly, gabapentin was associated with a reduction in the incidence of chronic pain and the incidence of nausea. CONCLUSIONS: Preoperative use of gabapentin was able to reduce acute and chronic postoperative pain, total morphine consumption and the occurrence of nausea following breast cancer surgery. Further studies should determine the optimal dose of gabapentin for pain control after breast cancer surgery.


Asunto(s)
Aminas/uso terapéutico , Neoplasias de la Mama/cirugía , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Mastectomía/efectos adversos , Morfina/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Aminas/administración & dosificación , Dolor Crónico/complicaciones , Dolor Crónico/epidemiología , Ácidos Ciclohexanocarboxílicos/administración & dosificación , Femenino , Gabapentina , Humanos , Morfina/administración & dosificación , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Cuidados Preoperatorios/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido gamma-Aminobutírico/administración & dosificación
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