RESUMEN
BACKGROUND: n-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health. METHODS: Randomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42â weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency. FINDINGS: Low-dose fish oil (3 capsules/day, 1080â mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors. INTERPRETATION: In this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080â mg/day) in drug resistant epilepsy. TRIAL REGISTRATION NUMBER: NCT00871377.
Asunto(s)
Ácidos Docosahexaenoicos/uso terapéutico , Resistencia a Medicamentos/efectos de los fármacos , Ácido Eicosapentaenoico/uso terapéutico , Epilepsia/tratamiento farmacológico , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Ácidos Docosahexaenoicos/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Ácido Eicosapentaenoico/efectos adversos , Epilepsia/dietoterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Most patients with major depressive disorder (MDD) do not recover with initial pharmacotherapy, and many pursue combination treatments. Combining a medication with neuromodulation offers an alternative to purely pharmacologic strategies. In prior open and double-blind controlled trials for drug-resistant epilepsy, adjunctive external trigeminal nerve stimulation (eTNS) was found to be safe and well tolerated, to significantly reduce seizures, and to be associated with an improvement in depressive symptoms. Here, we present a comprehensive description of the first open pilot investigation in MDD. In this 8-week trial, eleven adults with unipolar MDD received nightly stimulation (V(1) branch). All entered with moderate to severe symptom levels despite at least two antidepressant medication trials in this episode. All the eleven adults completed the acute trial, without serious adverse events. Symptoms of depression improved significantly, whether assessed with clinician- or self-rated scales (all p < 0.01; effect sizes d 1.0-1.8), as did quality of life (p < 0.02). Four of the 11 achieved remission. These improvements from nightly adjunctive eTNS in treatment-resistant depression merit replication under double-blind conditions.
Asunto(s)
Trastorno Depresivo Mayor/terapia , Terapia por Estimulación Eléctrica , Nervio Trigémino/fisiología , Enfermedad Aguda , Adulto , Análisis de Varianza , Trastorno Depresivo Mayor/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Factores de Tiempo , Resultado del TratamientoRESUMEN
Modulation of brain activity via trigeminal nerve stimulation is an emerging therapy in drug-resistant epilepsy. This cranial nerve also projects to structures implicated in depression (such as the nucleus tractus solitarius and locus coeruleus). We examined the effects of external trigeminal nerve stimulation in major depressive disorder as an adjunct to pharmacotherapy. Five adults (mean age 49.6, SD 10.9, three females and two males) participated in an 8-week open-label outpatient trial; all had persistent symptoms despite adequate pharmacotherapy, with a mean score on the 28-item Hamilton Depression Rating Scale of 25.4 (SD=3.9) at entry. Nightly stimulation over the V(1) branch was well tolerated. Both the clinician-rated 28-item Hamilton Depression Rating Scale (P=0.006) and the self-rated Beck Depression Inventory (P=0.0004) detected significant symptomatic improvement. This novel neuromodulation approach may have use as an adjunct to pharmacotherapy in major depressive disorder. Additional larger trials are needed to delineate efficacy and tolerability with greater reliability.
Asunto(s)
Trastorno Depresivo Mayor/terapia , Terapia por Estimulación Eléctrica/métodos , Nervio Trigémino/fisiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Resultado del Tratamiento , Adulto JovenRESUMEN
Political advertisements can shift attitudes and behaviors to become more exclusionary toward social out-groups. However, people who engage in an antidiscrimination exercise in the context of an experiment may respond differently to such ads. What interventions might foster inclusive attitudes in the presence of political communications about social policy issues like transgender rights? We examined two scalable antidiscrimination exercises commonly used in applied settings: describing a personal narrative of discrimination and perspective-taking. We then showed people political ads that are favorable or opposed to transgender rights to determine whether those interventions moderate how receptive people are to the messages. Relying on two demographically representative survey experiments of adults in the United States (study 1 N = 1,291; study 2 N = 1,587), we found that personal recollections of discriminatory experiences did not reduce exclusionary attitudes, but perspective-taking had some effects, particularly among those who fully complied with the exercise. However, both studies revealed potential backfire effects; recalling a discriminatory experience induced negative attitudes among a subset of the participants, and participants who refused to perspective-take when prompted also held more negative attitudes. Importantly, political ads favorable toward transgender rights consistently resulted in more positive attitudes toward transgender people. Future work needs to carefully examine heterogeneous responses and resistance to antidiscrimination interventions and examine what particular aspects of the political ads induced the attitude change.
RESUMEN
BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in those with drug-resistant epilepsy (DRE). There is a need for inventories and biomarkers associated with the risk for SUDEP. OBJECTIVE: To explore the revised SUDEP Risk Inventory (SUDEP-7) in a cohort with DRE and determine the association with Heart Rate and other covariates. METHODS: Twenty-five subjects with severe DRE were enrolled in a clinical trial for epilepsy. Baseline demographics, duration of epilepsy, seizure types, seizure frequency, seizure severity, AEDs, and vital signs were collected. Heart rate variability (HRV) was calculated from 1-h recordings of ECG. A SUDEP Risk Inventory (SUDEP-7) was administered, which included seven validated and weighted risk factors initially identified by Walczak et al. as factors associated with SUDEP risk. RESULTS: The total score on the revised SUDEP-7 ranged from 1 to 7, mean = 3.4 (SD 1.8). The SUDEP Risk Inventory score was inversely correlated with RMSSD (Pearson r = -0.45, p = 0.027). The following variables were significantly associated with RMSSD: epilepsy duration (p = 0.02), age (p = 0.03), and developmental intellectual disability (p < 0.001). The correlation between RMSSD and SUDEP-7 tended to persist also after the adjustment for patient age (r = -0.40, p = 0.05). Two subjects died of SUDEP: their SUDEP-7 scores were above average and in the upper twenty-fifth and fiftieth percentiles, respectively (6 and 4, mean = 3.4). CONCLUSION: RMSSD, a measure of low frequency HRV, was significantly associated with SUDEP Risk Inventory (SUDEP-7) scores. Using a multivariate model, the covariates of developmental intellectual disability, age, and duration of epilepsy were also significantly associated with decreased HRV. The correlation between decreased HRV and a higher SUDEP-7 score remained unchanged even after the adjustment for patient age. The results suggest that older age, greater duration of epilepsy, and the presence of developmental intellectual disability may increase the risk of SUDEP through their direct influence on decreasing the vagus nerve-mediated HRV. Further validation of the SUDEP-7 inventory is indicated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00871377.