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ABSTRACT
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 ofstimulants. 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.
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