Stimulants ADHD treatment

Jensen, P., Kettle, L., Roper, M., Sloan, M., Dulcan, M., Hoven, C., Bird, H., Bauermeister, J., and Payne, J. (1999) Are stimulants overprescribed Treatment of ADHD in 4 US communities./ Am Acad Child Adolesc Psychiatry 38 797-804. 

The Multimodal Treatment of ADHD (MTA) Study, a large, multisite study of ADHD treatment (MTA Cooperative Group, 1999), highlights the importance of this therapeutic alliance. When outcome was measured only in terms of the child s inattention, stimulant medication alone did as well as medication plus psychosocial treatment. However, the combination of medication and psychotherapy had the best outcome in parent satisfaction and in reducing disruptive behaviors (Hinshaw et ah, 2000), which are important factors in longer-term compliance with treatment and outcome. 

Tricyclic antidepressants (TCAs) are not as well studied as stimulants for treatment of ADHD even in normally developing children and adolescents, but are well enough studied that they are established as a second-line treatment. There are no controlled studies of TCAs in MR. Two case series reported ADHD symptom improvement, but seizures were a problem in one series (Szymanski, 1998). 

The reason that pharmaceutical companies would support the view that ADHD has a biological cause seems obvious. A biological cause means that a drug (usually Ritalin) is the treatment of choice, and selling stimulants is a profitable business. The DEA estimates that pharmaceutical companies earn approximately 450 million a year from the sales of stimulants, and nearly all of the stimulants sold legally in the United States are prescribed for ADHD treatment. 

Over the last several years, NIMH has funded a cohort of dedicated stimulant/ADHD advocates to conduct an expensive, nationwide, longterm study under naturalistic conditions in the community to prove the effectiveness of stimulants in treating so-called ADHD (Jensen et ah, 2001). The list of authors includes Peter Jensen, Stephen Hinshaw, James Swanson, Larry Greenhill, and even Keith Conners. It was as if the aging Stimulant Club had gone on government relief to produce the NIMH Multimodal Treatment Study of ADHD (MTA), whose results continue to be published. 

Strattera (atomoxetine), the supposedly safer nonstimulant treatment for ADHD, turned out to be highly stimulating and is the only ADHD treatment required to carry a black-box warning, with a heading about how it can cause Suicidal Ideation in Children and Adolescents (chapter 11). 

Atomoxetine, bupropion, and TCAs are second-line alternatives to the stimulants for treatment of ADHD in children, teens, and adults. The potential benefits of these agents in comparison with stimulants include reduced risk of abuse and somewhat lower potential for sleep disturbance. TCAs are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. The monoamine oxidase inhibitor tranylcypromine is effective but used infrequently due to the potential for dangerous drug and dietary interactions. Selective serotonin reuptake inhibitors (SSRIs) are not effective for ADHD. ... 

Pemoline [2152-34-3] (24), stmcturally dissimilar to amphetamine or methylphenidate, appears to share the CNS-stimulating properties. As a consequence, pemoline is employed in the treatment of ADHD and of narcolepsy. There are several other compounds that are stmcturally related to amphetamines, although not as potent and, presumably, without as much abuse potential. These compounds also have anorexic effects and are used to treat obesity. Some of the compounds available are phentermine [122-09-8] fenfluramine [458-24-2] and an agent that is available over-the-counter, phenylpropanolamine [1483815-4] (26). 

Grace AA (2001) Psychostimulant actions on dopamine and limbic system function relevance to the pathophysiology and treatment of ADHD. In Solanto MV, Arnsten AFT, Castellanos FX (eds) Stimulant drugs and ADHD, Oxford University Press, pp 134—157... 

Behavioral therapy can be used to treat patients with ADHD however, it is generally not recommended as first-line monotherapy.8 Several studies have demonstrated that treatment with medication alone is superior to behavioral intervention alone in improving attention.12 However, behavioral therapy in combination with stimulant therapy was better at improving oppositional and aggressive behaviors.12 Behavioral modification involves training parents, teachers, and caregivers to change the physical and social environment and establishment... 

Atomoxetine (9), a selective NRI, is the first non-stimulant drug approved for the treatment of ADHD [22]. Interestingly, in a recent 12-week, randomized, double blind, placebo-controlled trial in 30 obese women, atomoxetine demonstrated modest short-term weight loss efficacy relative to placebo [23]. 

The dopamine transporter has been a target for developing pharmacotherapies for a number of CNS disorders including ADHD, stimulant abuse, depression and Parkinson s disease. Several excellent reviews in this area have been recently published [28-30]. The dopamine reuptake inhibitor methylphenidate has been successfully used for decades in the management of ADHD in children and adolescents. It remains a first-line treatment along with amphetamine for this disorder [31,32]. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Dextroamphetamine (Dexedrine). Dextroamphetamine is the second most widely used stimulant and the most commonly used amphetamine in the United States. It is about twice as potent as methylphenidate and should be initiated in the treatment of ADHD at 2.5 mg taken twice daily with breakfast and lunch. Like other stimulants, the benefits of dextroamphetamine can be seen almost immediately. With weekly visits while starting treatment, the dose can be increased in 2.5-5 mg increments until the effective dose is found. Because dextroamphetamine is also slightly longer acting than methylphenidate, patients may be less likely to need an evening dose. If an after-school dose is used, then like methylphenidate it should be 25-50% of the daytime dose. 

Modafinil (Provigil). The newest stimulant, modafinil, is not, pharmacologically, a true stimulant. Nevertheless, it is an effective treatment for narcolepsy at doses from 200 to 400mg/day. Several studies indicate that modahnil has little potential for abuse and is easier to tolerate than other stimulants. Modafinil has been studied in the treatment of ADHD. Though not approved for marketing by the FDA at the time of this writing, it may gain the indication in the near future. 

Serotonin-Boosting Antidepressants. Antidepressants that enhance serotonin activity in the brain have also been studied in ADHD. In particular, fluoxetine (Prozac) and the serotonin-selective TCA clomipramine (Anafranil) have been the most extensively evaluated, with mixed success. They provide some benefit for aggression and impulsivity but don t significantly improve the poor attention of ADHD. As a result, the SSRls and other serotonin-boosting antidepressants do not appear to be effective first-line treatments for ADHD. Conversely, depressed patients without ADHD often show improvements in symptoms of concentration and attention when treated with a SSRI. Although SSRls are not widely used in the treatment of ADHD, they may be worthy of consideration in ADHD patients whose impulsivity is not controlled by stimulants alone. Those with comorbid conduct disorder or ODD who are prone to agitation and at times violent outbursts may be helped by the addition of a SSRI. 

Close to 70% of children with ADHD will respond to a stimulant. When the child is not helped by the first stimulant that is prescribed, there is still a good chance of responding to a different one. If an initial trial of methylphenidate isn t successful, then switching to dextroamphetamine or Adderall is a reasonable strategy. If dextroamphetamine or Adderall was used first and did not work well, then we recommend switching to methylphenidate. Because dextroamphetamine and Adderall are more similar, it makes less sense to switch between these two. We do not recommend pemoline as a first-line treatment. 

Starting Treatment in Adults with ADHD. Beginning treatment of an adult is not significantly different from doing so in a child. The stimulants and atomoxetine remain the most effective medications. Methylphenidate, dextroamphetamine, and Adderall appear to be equally effective in group trials, but individuals may respond preferentially to one medication or the other. 

Attention deficit hyperactivity disorder (ADHD) For the treatment of ADHD in patients 6 years of age and older. Dexmethylphenidate is indicated as an integral part of a total treatment program for ADHD that may include other measures (eg, psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients. Stimulants are not intended for use in the patient who exhibits symptoms secondary to environmental factors or other primary psychiatric disorders, including psychosis. 

A second study appears to support the Dougherty study. Ten stimulant-naive adults with ADHD were studied before and after 4 weeks of daily treatment with methylphenidate by SPECT with [Tc-99m]-... 

The most common treatments for ADHD are the stimulant medications methylphenidate and amphetamines. Secondary medications include dopaminergic or noradrenergic reuptake blockers (e.g., a tamoxetine) and ttj-adrenergic agonists. These treatments are reviewed in this volume (see Chapters 20, 21, 24, and 35). Thus, only brief reference will be made here to the possible effects these compounds may have vis-a-vis modulation of attentional circuits. These ideas are summarized in Figure 8.2. 

The increasing use of stimulants in the United States to treat attention deficit hyperactivity disorder (ADHD) has aroused parental concern and compelled both medical professionals and the media to question the safety and efficacy of this type of treatment. Because ADHD is among the most common reasons for seeking mental health services for children, these questions are more pertinent than ever. This chapter will examine the history of stimulant use, the mechanism of action, pharmacokinetics, side effects, and issues related to their clinical use in children and adolescents. More detailed information on clinical applications is provided in Section III. 

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