¿Cómo afecta el metilfenidato al circuito de activación por defecto? Revisión sistemática / How does methylphenidate affect default mode network? A systematic review

Introducción. El metilfenidato es un fármaco ampliamente usado como tratamiento del trastorno por déficit de atención/hiperactividad (TDAH) y otros trastornos neuropsiquiátricos. La dificultad para mantener la atención de forma prolongada y la deficiente ejecución de tareas que caracterizan a tales trastornos se han vinculado a la disfunción del circuito de activación por defecto --default mode network (DMN)--, revelado en estudios de resonancia magnética funcional. En los individuos sanos, el DMN y la red orientada a tareas (task-positive network) presentan una relación inversa. Se ha planteado que el metilfenidato revertiría la escasa desactivación del DMN durante la ejecución de tareas que caracteriza a los trastornos de la atención y del control inhibitorio, normalización que a su vez mejoraría la ejecución de las tareas. Pacientes y métodos. Con objeto de examinar la hipótesis de que este fármaco propicia tal desactivación, se llevó a cabo una revisión sistemática de la bibliografía. Resultados. Doce estudios se incluyeron finalmente en la revisión. Para ello, debían haber medido los efectos de la administración del metilfenidato sobre la actividad del DMN. Once estudios mostraron indicios de mejora atribuible al metilfenidato en áreas cerebrales vinculadas a dicho circuito. Los resultados indican la normalización de los circuitos cerebrales en los pacientes con disfunción del DMN. Conclusiones. Los hallazgos preliminares ofrecen indicios sólidos de que el metilfenidato mejora la disfunción del DMN presente en el TDAH y otros trastornos neuropsiquiátricos. Se precisan nuevos estudios que diluciden los pormenores de este efecto y mejoren la comprensión sobre los mecanismos de acción del metilfenidato

Introduction. Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention deficits and poorer task performance in these disorders have been associated with default mode network (DMN) dysfunction in fMRI studies. DMN is a set of brain areas more activated during the resting-state. Under the execution of external tasks, there is an attenuation of DMN activity. In healthy individuals DMN and task-positive network are anticorrelated. It has been suggested that methylphenidate could normalize the attenuated task-related DMN deactivation in attention- and inhibitory control-related disorders and that such normalization could improve task performance. Patients and methods. To explore the hypothesis of DMN deactivation after methylphenidate administration, we conducted a systematic review of the literature. Results. After a systematic search, 12 studies were included in this review. For eligibility, studies were required to measure the effects of methylphenidate administration on the DMN activity. Eleven studies showed evidence of MPH-induced improvements in brain areas related to DMN. The results suggest a normalization of brain circuits in individuals with DMN dysfunction. Conclusions. Our preliminary findings strongly suggest methylphenidate improves DMN dysfunction presented in ADHD and other neuropsychiatric disorders. Further studies are needed to better understand this effect and expand comprehension of methylphenidate action mechanisms

Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of neuropsychological impairments. The relationship between these neuropsychological deficits and the defining symptoms of ADHD seems more complex than originally thought. Methylphenidate (MPH) is an effective treatment for ADHD symptoms, but its impact on cognition is less clearly understood. METHODS: With a common systematic search strategy and a rigorous coding and data extraction strategy across domains, we searched electronic databases to identify published placebo controlled trials that compared MPH and placebo on executive and nonexecutive memory, reaction time, reaction time variability and response inhibition in children and adolescents (5-18 years) with a formal diagnosis of ADHD. RESULTS: Sixty studies were included in the review, of which 36 contained sufficient data for meta-analysis. Methylphenidate was superior to placebo in all five meta-analyses: executive memory, standardized mean difference (SMD) .26, 95% confidence interval (CI): -.39 to -.13; non-executive memory, SMD .60, 95% CI: -.79 to -.41; reaction time, SMD .24, 95% CI: -.33 to -.15; reaction time variability, SMD .62, 95% CI: -.90 to -.34; response inhibition, SMD .41, 95% CI: -.55 to -.27. CONCLUSIONS: These data support the potentially important effects of MPH on various aspects of cognition known to be associated with ADHD. Consideration should be given to adding cognitive outcomes to the assessment of treatment outcome in ADHD, considering the complexity of the relationship between ADHD symptoms and cognition.