The use of prolonged-release melatonin in circadian medicine: a systematic review.

INTRODUCTION: Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is designed to mimic the natural physiological pattern of melatonin release. In circadian medicine, PRM can be used to treat sleep and circadian rhythm disorders, as well as numerous organic diseases associated with sleep disorders. EVIDENCE ACQUISITION: This systematic review analyzed 62 studies and adhered to the PRISMA guidelines, examining the effectiveness of PRM in organic pathologies and mental disorders. EVIDENCE SYNTHESIS: The main evidence concerns primary insomnia in subjects over the age of 55, showing significant improvements in sleep quality. In neurodevelopmental disorders, there is evidence of a positive impact on sleep quality and quality of life for patients and their caregivers. PRM shows efficacy in the treatment of sleep disorders in mood disorders, schizophrenia, and neurocognitive disorders, but requires further confirmation. The additional use of PRM is supported for the withdrawal of chronic benzodiazepine therapies. The tolerability and safety of PRM are excellent, with ample evidence supporting the absence of tolerance and dependence. CONCLUSIONS: Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.

Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

C. elegans: a prominent platform for modeling and drug screening in neurological disorders.

INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.

Tackling myelin deficits in neurodevelopmental disorders using drug delivery systems.

Interest in myelin and its roles in almost all brain functions has been greatly increasing in recent years, leading to countless new studies on myelination, as a dominant process in the development of cognitive functions. Here, we explore the unique role myelin plays in the central nervous system and specifically discuss the results of altered myelination in neurodevelopmental disorders. We present parallel developmental trajectories involving myelination that correlate with the onset of cognitive impairment in neurodevelopmental disorders and discuss the key challenges in the treatment of these chronic disorders. Recent developments in drug repurposing and nano/micro particle-based therapies are reviewed as a possible pathway to circumvent some of the main hurdles associated with early intervention, including patient's adherence and compliance, side effects, relapse, and faster route to possible treatment of these disorders. The strategy of drug encapsulation overcomes drug solubility and metabolism, with the possibility of drug targeting to a specific compartment, reducing side effects upon systemic administration.

Tratamientos disruptivos en psiquiatría / Disruptive treatments in psychiatry

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Nuevos tratamientos farmacológicos en el TDAH. A propósito de un caso clínico / New pharmacological treatments for ADHD. A case report

El Trastorno por Déficit de Atención/Hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo más prevalentes en la infancia que frecuentemente se mantiene en la adolescencia y edad adulta. Los psicoestimulantes son generalmente el tratamiento farmacológico de primera línea para el TDAH, aunque alguno de estos pacientes no consiguen una remisión sintomática completa, especialmente los que tienen comorbilidad con el Trastorno Negativista Desafiante (TND). En estos casos, hay cada vez una mayor evidencia de que la combinación de psicoestimulantes y medicamentos no específicos para manejar el TDAH puede ser útil. La Guanfacina de liberación prolongada (GXR, Guanfacine Extended Release), un nuevo fármaco no psicoestimulante que actúa como agonista alfa 2 adrenérgico, ha sido aprobado recientemente por la Agencia Europea de Medicamentos como un nuevo tratamiento para el TDAH. En España se ha empezado a comercializar a finales de enero 2017. El objetivo de este estudio es evaluar la eficacia y tolerabilidad de la GXR administrada conjuntamente con dimesilato de lisdexanfetamina en un paciente con Trastorno por Déficit de atención e Hiperactividad (TDAH) y Trastorno Negativista Desafiante(TND)

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood, which shows diagnostic persistence and morbidity into adulthood. Psychostimulants are generally first-line pharmacotherapy for ADHD, but some patients do not achieve symptomatic remission, especially those who have Oppositional Defiant Disorder (ODD) comorbidity. In those cases, there is growing evidence that a combination of psychostimulants and nonscheduled medications to manage ADHD, may be useful. The alpha-2 adrenergic agonist guanfacine extended release (GXR), a non-stimulant treatment, has recently been approved by the European Medicines Agency (EMA) as new therapeutic option for ADHD. In Spain it has been available from the end of January 2017. The aim of this study is to test the efficacy and tolerability of a combined therapy of psychostimulant (lisdexamfetamine) and GXR in a patient with ADHD and ODD

Eficacia y seguridad de aripiprazol en el tratamiento de niños y adolescentes con trastornos psiquiátricos / Efficacy and safety of aripiprazole in the treatment of children and adolescents with psychiatric disorders

Objetivo: revisar los datos disponibles sobre la eficacia y la seguridad de aripiprazol (APZ) en el tratamiento de trastornos mentales en niños y adolescentes. Metodología: revisión de la literatura de todos los artículos publicados en inglés o castellano en PubMed y Google Scholar hasta mayo de 2012 sobre eficacia y la seguridad de APZ en niños y adolescentes. Resultados: el APZ ha demostrado eficacia en el tratamiento de la esquizofrenia, el trastorno bipolar y las alteraciones del comportamiento asociadas al trastorno del espectro autista. Asimismo, hay datos que sugieren eficacia del APZ en el trastorno por déficit de atención e hiperactividad, trastornos por tics, trastorno obsesivocompulsivo, trastorno de conducta y otros trastornos, como trastorno delirante o trastorno por estrés postraumático. APZ tiene un perfil de seguridad favorable, con menos aumento de peso que otros antipsicóticos (NNH para aumento de peso igual o mayor de 7%: olanzapina 3, risperidona 6, quetiapina 9, y APZ 12), mínimos efectos cardiometabólicos y ausencia de aumento de prolactina. El principal efecto secundario descrito es la acatisia. Conclusiones: en el conjunto de los antipsicóticos, el APZ es un fármaco eficaz y seguro, con un perfil de tolerabilidad muy favorable. Sin embargo, los datos disponibles en niños y adolescentes son todavía escasos y son necesarios más ensayos clínicos controlados en esta población

Objective: to review available data on efficacy and safety of aripiprazole (APZ) in the treatment of mental disorders in children and adolescents. Methods.: comprehensive review of all articles published in English or Spanish in PubMed and Google Scholar until May 2012 on efficiency and safety of APZ in children and adolescents. Results: APZ has shown efficacy in the treatment of schizophrenia, bipolar disorder and behavioral disturbances associated with autistic spectrum disorder. There are also data suggesting efficacy of APZ in attention deficit/ hyperactivity disorder, tic disorders, obsessive-compulsive disorder, conduct disorder and other disorders such as delusional disorder or PTSD. APZ has a favorable safety profile, with less weight gain than other antipsychotics (NNH for weight gain equal to or greater than 7%: olanzapine 3, risperidone 6, quetiapine 9 and APZ 12), minimal cardiometabolic side-effects and no increase of prolactin. The main side effect is akathisia. Conclusions.: among the group of antipsychotics, APZ is an effective and safety drug with a favorable tolerability profile. However, available data in children and adolescents are still scarce and more controlled clinical trials in this population are warranted

Psicofarmacología e infancia. ¿Dónde reside la ética? / Psychopharmacology and childhood: Where ethics are?

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Psicofármacos en niños y adolescentes: revisión y situación actual / Psychotropics in children and adolescents: revision and state of the art

En 2004 la Agencia Española de Medicamentos (AEMPS) recomendaba no utilizar ISRS en niños y adolescentes deprimidos por falta de eficacia, y por aumentar el riesgo de conductas suicidas. Además, nos recordaba que ninguno de los ISRS tienen la indicación aprobada para la depresión en este grupo de población. He revisado que otros psicofármacos empleados habitualmente en niños y adolescentes no tienen una indicación autorizada en su ficha técnica y muestro cuál sería la vía legal que se debe utilizar cuando consideramos que un fármaco es necesario y no está autorizado (AU)

In 2004 the Spanish Drug Agency (AEMPS) suggested not using ISRS in depressed children and adolescents dueto its lack of efficacy, and to an increase in the risk of suicidal behaviour. More over it reminded us that none of the ISRS has been approved indication for depression in this population group. I have reviewed articles where other psychotropics habitually used in children and adolescents do not have authorized approval on their technical registration form, and what should be the legal way to use when we consider that a drug is necessary and it is not authorized (AU)

Fármacos antidepresivos en niños y adolescentes / Antidepressant drugs in children and adolescents

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Neurolépticos atipicos en niños y adolescentes: últimas aportaciones / Atypical neuroleptics in children and adolescents: last results

La utilización de fármacos neurolépticos en el tratamiento de niños y adolescentes con enfermedades mentales es un hecho de larga data que va adquiriendo más apogeo en los últimos años gracias a la introducción en el mercado de nuevos antipsicóticos con un perfil de efectos secundarios más benigno que facilitan su prescripción en estas edades. Así, partiendo de la clozapina como antipsicótico atípico inicial, y siguiendo con otras sustancias como risperidona, olanzapina, quetiapina, o ziprasidona, se repasa la literatura nacional e internacional de los últimos años en cuanto a la utilización de estos fármacos en la patología psiquiátrica infantil. Trastornos muy diversos han sido foco de tratamiento con estas sustancias: desde las clásicas patologías psicóticas de los primeros años de la vida (autismo, trastornos del espectro autista, trastornos generalizados del desarrollo: TGD) o las psicosis de inicio más posterior (esquizofrenia de inicio muy precoz, trastorno bipolar de inicio en la infancia, depresiones psicóticas), al trastorno de la Tourette y más recientemente el TDAH o la patología de la conducta (trastorno disocial), como los más frecuentes. En este artículo se pretende realizar una revisión bibliográfica de los últimos tres años destacando las investigaciones más relevantes que hayan surgido (AU)

Agonistas Adrenérgicos en Psiquiatría Infantil: I. Clonidina / Adrenergic agonists in child psychiatry: I. Clonidine

Clonidina es un fármaco agonista de los receptores adrenérgicos alfa2 que, aunque no tienen aprobada indicaciones en Psiquiatría infantil, ha visto recientemente avalado su uso en patologías como el trastornos por déficit de atención con hiperactividad, tanto en monoterapia como asociado a metilfenidato, resultando especialmente efectiva si predomina la hiperactividad y el comportamiento agresivo. También hay estudios que la avalan en el trastorno oposicionista desafiante, trastorno de conducta y en la desintoxicación de opioides. Se estudian los trabajos que apoyan el uso de Clonidina en estas y otras patologías, así como la pauta de administración y los efectos adversos más frecuente (AU)

El efecto placebo y su uso clinico / The placebo effect ant its clinical use

El uso del placebo en Psiquiatría Infanto-Juvenil es poco frecuente, excepto en el contexto de la investigación farmacológica. Recientemente han surgido controversias respecto a su justificación ética y su utilidad científica. Sin embargo, en muchos estudios llama la atención el hecho de que, a pesar de que la molécula en estudio es significativamente más eficaz que el placebo, éste muestra resultados positivos en una proporción considerable. En el presente trabajo se analizarán su definición, los factores psicológicos y neurobiológicos que pueden subyacer a sus elevados índices de respuesta en algunos estudios y su posible utilidad en la clínica (AU)