Fármacos estimulantes y psiquiatría infantil. Una revisión de su aplicación en el trastorno por déficit de atención con hiperactividad en niños

• Autores: Gerardo García Maldonado
• Localización: Salud mental, ISSN 0185-3325, Vol. 26, Nº. 2, 2003, págs. 33-41
• Idioma: español
• Enlaces
  • Texto completo (pdf)
• Resumen
  • español

    En 1937, un descubrimiento casual sacó a la luz los efectos de las anfetaminas sobre la hiperactividad psicomotriz. Actualmente estos estimulantes se pueden adquirir para uso clínico y se prescriben para tratar el trastorno por déficit de atención con hiperactividad (TDAH) en la infancia, adolescencia y algunas veces en la edad adulta, aunque hay otros estados clínicos que pueden ser objeto de este tipo de prescripción médica, como es el caso de la narcolepsia.

    La información que existe sobre estos productos es extensa y su administración es en general la primera elección. Se ha observado que son sustancias efectivas en el corto plazo y, dado que son múltiples los estudios de investigación al respecto -además de la gran experiencia clínica acumulada durante los últimos años en su utilización-, se considera que hoy día se sabe más sobre estos productos que sobre cualquier otro psicofármaco de prescripción en niños.

    El aumento en el diagnóstico de TDAH parece ser reflejo de un aumento en el reconocimiento de este problema. Sin embargo, como también se ha generado un exagerado incremento en la administración de estimulantes, grupos antagónicos han manifestado que últimamente se les está dando un uso inapropiado. Estos conflictos producen sin duda desconcierto y temor entre los padres de los menores con TDAH, los educadores y los legisladores, lo que impone mayores retos al trabajo clínico diario del psiquiatra infantil.

    La decisión de prescribir estas sustancias se basa en la presencia de TDAH con síntomas suficientemente graves para causar alteraciones funcionales en el hogar o en la escuela.

    Si bien la medicación es una herramienta eficaz y muy documentada, algunos síntomas pueden no revertirse. Asimismo, hay padres de niños y adolescentes que se oponen al uso de los estimulantes, sobre todo cuando los efectos colaterales son importantes o la eficacia es limitada. Se recomienda aplicar siempre un criterio de riesgo-beneficio que debe explicarse a los familiares, y tomar siempre en cuenta que, para una buena adhesión al tratamiento, se debe contar con la colaboración de los padres, maestros y cuidadores en general. Al respecto se debe considerar que hay aspectos inherentes al desarrollo o a la psicopatología misma que pueden impedir la cooperación del paciente.

    La farmacocinética de los estimulantes se caracteriza por una rápida absorción, una baja unión a proteínas y un rápido metabolismo extracelular. Se considera que más de 80% del producto se excreta sin cambios y se logra una mayor biodisponibilidad si se ingiere después de los alimentos. Sin embargo, en el caso de la pemolina, la actividad metabólica es diferente.

    Los productos tradicionales son el metilfenidato y la nfetamina, disponibles en preparados de acción larga y acción corta. La necesidad de utilizar estimulantes de acción prolongada deriva de las características particulares de los preparados de acción rápida, que requieren tomas frecuentes que a veces es difícil administrar, lo que repercute en la adhesión terapéutica.

    En Estado Unidos, la industria farmacéutica ha estado desarrollando un tipo de metilfenidato con patrones de liberación osmótica. Múltiples estudios demuestran que la respuesta clínica a los estimulantes es de hasta 70%. Sin embargo, es importante señalar que en general se acepta que los efectos de estos compuestos no son paradójicos ni específicos del TDAH. El tratamiento siempre deberá ser individualizado; la administración de dosis fijas es la práctica más utilizada por los clínicos. Los efectos terapéuticos establecidos para los estimulantes actúan sobre las áreas motora, social y cognoscitiva, además de los efectos ya conocidos sobre los principales síntomas del TDAH.

    Los efectos no deseados que se pueden presentar al usar estos compuestos, se resuelven las más de las veces con ajustes en dosis y horarios de administración. De acuerdo con la referencia de los autores, se deberá tomar en cuenta la comorbilidad psiquiátrica en el TDAH para los fines de la prescripción médica de los estimulantes. Asimismo, pese a todas las opiniones encontradas, por el momento no hay evidencia del desarrollo de tolerancia o dependencia a estos productos. El objetivo de este artículo es revisar algunos de los aspectos más relevantes sobre los fármacos estimulantes.

  • English

    In 1937 a serendipitous observation discovered the effects of amphetamines on disruptive behavior. Today, stimulant medications are available for clinical use and they are prescribed for the treatment of attention deficit/hyperactivity disorder (ADHD) in the childhood and adolescence, and sometimes in adults, but another conditions, such as narcolepsy, may be also the focus of stimulants use. Literature on stimulant medications is voluminous and in most cases a stimulant is the first-choice medication. These products are clearly effective at least in the short-term. After large numbers of research studies and 60 years of clinical experience in patients, there is more knowledge about stimulant use in children and adolescents than about any other drug. The increase in the diagnosis of ADHD over the past decade seems to reflect an increase in the recognition of the disorder and has led in turn to a dramatic increase in the prescription of stimulants. Nowadays, methylphenidate is the drug of choice in the treatment, although skeptics people in the United States argue that the increases indicate an inappropriate use of these products. The diverse and conflicting opinions about this topic have resulted in confusion for families, care providers, educators and policymakers, and child psychiatrists face a significant challenge in clinical practice. The decision to medicate is based on the presence of ADHD and persistent target symptoms sufficiently severe to cause functional impairment at school and usually also at home and with peers. Although medication is the most powerful and best documented intervention, some symptoms may not respond to it. Some parents and patients are resistant to the use of medication and some patients experience unacceptable side effects or limited efficacy. The careful clinician balances the risks of the untreated disorder and the expected benefits of medication as compared to other treatments. A baseline for target symptoms is useful before starting medication. Faithful adherence to a prescribed regime requires cooperation among the parents, the patient, school staff and often additional caretakers. Medications may be used incorrectly or completely avoided because of parental factors such as lack of perceived need for the drug, carelessness, inability to afford medication, misunderstanding of instructions, complex schedules of administration and family dynamics. Both developmental and psychopathological factors may impede the patient’s cooperation. The pharmacokinetics of the stimulants is characterized by rapid absorption, low plasma protein binding and rapid extracellular metabolism. Although several pathways are involved in their metabolism, up to 80% may be excreted unchanged in the urine. Both absorption and bioavailability may increase if stimulants are taken after meals. Traditional products like methylphenidate (MPH) and dl-amphetamine (AMP) have been available in two versions: short-acting and long-acting; in the case of pemoline, the pharmacology is different. The need for long-duration stimulants emanates from a variety of concerns like the time-response characteristics of standard products, compliance and schools policies which may prohibit its administration. Another problem is when some adolescents avoid cooperating because of fear of ridicule. Long-duration versions of stimulant medications have been available for more than a decade and help practitioners with adherence to treatment schedule, but some clinicians find that these products are less effective than the short-acting version. Pediatric psychopharmacological drug development by the pharmaceutical industry has increased greatly. New drugs are targeted to children with ADHD and these new products have been shown to be a useful alternative to older stimulant medications. An example of this is the new medication called OROS-MPH. Given once a day, this drug produces an ascending pattern plasma drug level generated by the caplet’s osmotically released, timed drug-delivery system. More than 160 controlled studies involving more than 5,000 school-age children demonstrated a 70% response rate when a single stimulant was tried. Stimulant treatment leads to improvements in both ADHD symptoms and associated conditions as compared to non-pharmacological treatments. Stimulants improve behavior and attention both in children with other disorders and in normal subjects, so these drug effects are neither “paradoxical” nor specific for ADHD. The duration of medication treatment is determined individually because treatment may be required through adolescence and into adulthood. Research literature suggests two divergent methods to choose a starting dose of MPH for a particular child with ADHD: the weight-adjusted method and the fixed dose method. The latter is the typical practice used in the United States. Clinicians should base decisions to change doses on the scores of one of the many standardized validated rating scales for assessing ADHD behavior. In addition to improving the core symptoms of inattention, hyperactivity, and impulsivity, the specific effects documented for groups of ADHD stimulant responders are on motor, social, and cognitive domains. Whether an individual patient is considered a positive responder depends on the balance of improvement in target symptoms with severity of side effects. Almost all stimulant-related sideeffects reported are rare and short-lived and are responsive to dose or timing adjustments. In placebo-controlled studies of stimulants, parents report delay of sleep onset, reduced appetite, weight loss, tics, stomach-ache, headache, and jitteriness as the more often side effects. The risk of abuse and the possibility of tolerance or drug refractoriness are greater in adults than in children but are rare still. Once the clinician and family agree to stimulant treatment, several steps must be planned. The parent should be educated first about the natural course of the disorder and the benefit-to-risk ratio of the medication treatment. The physician then needs to decide on a starting dose and a titration regimen. Predicting drug response in an individual child is difficult and most research shows that no neurological, physiological or psychological measures are reliable predictors. Even within history of abuse of illicit drugs, tics, seizure disorders and anxiety as comorbid disorders, the use of stimulants for ADHD may nor represent an absolute contraindication. The evaluation and management of the stimulants used for ADHD require input and cooperation from the patient, whether adolescents or adult, making the clinician’s role as coordinator or case manager vital to the treatment. ADHD has an extended course, requiring continuous treatment planning to deal with the effectiveness of current treatment and the emergence of new problems. The use of medications should be individualized, according to the pattern of target symptoms and strengths identified in the evaluation, but the reports from parents and teachers will be important to monitor the progress in academic or personal performances. The goal is to help parents understand their child and his/her problems, and to modify practices that may exacerbate his/her difficulties. The most troubling difficulty with pharmacological treatment of ADHD is the lack of maintenance of effects once treatment has been discontinued and the failure of generalization to settings in which treatment has not been active. Plans should be designed with these problems in mind. Taking into consideration that the assessment and treatment of the patient may be appropriate the objective of this paper will be to review the more important topics about the stimulants.