STIMULANTS ADDED TO ATX

Some patients with ADHD gain a positive response from treatment with ATX alone but continue to suffer with additional impairments that are highly problematic.

Case 3

Frank, a 14-year-old ninth grader, had been diagnosed with ADHD-combined type in seventh grade. He was tried on MPH at that time but did not respond well to doses of 10 or 15 mg tid. When the dose was increased to 20 mg tid, he experienced marked improvement in symptoms of both inattention and hyperactivity/impulsivity, but he refused to continue because this higher dose caused severe blunting of affect and anorexia. Subsequently he was tried on mixed salts of amphetamine and on OROS MPH. With all of these stimulants, the dose required to produce significant alleviation of ADHD symptoms caused the same intolerable side effects.

Frank was then tried on nortriptyline (NT) up to 80 mg hs. On this regimen his hyperactive and impulsive symptoms were markedly alleviated, but his inattention symptoms continued to be problematic. and he disliked the regimen because it caused him to feel that he had lost his "sparkle," a less severe blunting of affect than on stimulants, but still uncomfortable enough to make him reluctant to take the medication. Over 2 years, he had several episodes of interrupting his treatment with NT to avoid side effects, being frustrated by declining grades and behaviour problems, and then unhappily resuming treatment on the NT regimen.

Frank requested a trial of ATX immediately after it became available. His NT was discontinued, and he was started on 25 mg qam for 1 week, after which the dose was increased to 50 mg and then, 1 week later, to 80 mg qam. After minor gastrointestinal complaints and some somnolence in the first week, no adverse effects were reported. Frank initially reported no benefit, but after 3 weeks he noticed that he felt more calm throughout the day. His parents and teachers reported improved behaviour throughout the day, but they and Frank noted that he continued to show much difficulty in sustaining concentration for academic tasks.

In week 6, Frank's regimen of ATX 80 mg qam was divided into 40 mg bid and then augmented with OROS MPH 18 mg qam. He reported that this slightly improved his ability to remember what he had read and to focus on his schoolwork. At his request, the dose was increased to OROS MPH 27 mg qam with the ATX 40 mg bid. Frank has continued on this regimen for 4 months with no adverse effects.

He reports that on this regimen he feels "like my regular self," and his grades have improved in all subjects. Frank's intermittent disruption of his treatment with NT illustrates an important problem that commonly occurs, especially with adolescent patients. Uncomfortable side effects such as blunting of affect can significantly interfere with treatment compliance, even when the regimen significantly improves target symptoms. The combination of ATX and OROS MPH alleviated this problem that had threatened to totally disrupt Frank's treatment. This combined regimen developed in collaboration with Frank also resulted in better control of the wider range symptoms targeted for treatment.

Case 4

Six-year-old George was diagnosed with ADHD-combined type and oppositional defiant disorder after 3 months in full-day kindergarten. His teacher complained that George refused to follow directions and was unable to sustain attention to tasks. George's parents reported that over several years he had been increasingly oppositional at home, so much that they were unable to get any babysitter to return for a second time. He often fought with neighbourhood children and was argumentative and disrespectful to his parents and other adults. Parents also reported that since early childhood George had experienced chronic difficulty in falling asleep. Despite their efforts to calm him, he was unable to settle into sleep until 10 to 11:30 p.m.

George was started on ATX 18 mg qam. Initially he complained of stomach-ache, but this dissipated within a few days. Dose was increased to 36 mg qam after 1 week. After 2 weeks, parents reported that George had begun to settle down more easily in the evening and was falling asleep without much difficulty by 8:30 p.m. They also noted improvement in his compliance with morning routines and getting off to school. After 3 weeks, the teacher reported that George was more cooperative in following directions and had a better attitude with other children but noted that he still had much difficulty in sustaining attention to stories, play, or reading exercises.

In that the recommended ATX dosing limit for George's weight had been reached, a trial of Adderall-XR 5 mg qam was added to the ATX regimen. This improved George's behaviour further and increased his ability to sustain attention in school, but it also caused increased difficulty in falling asleep. The ATX dose was then split so that George received 18 mg ATX with the morning dose of stimulant and 18 mg ATX at dinnertime. This recaptured the improvement in sleep. George has continued on this regimen for 3 months, with marked improvement at home and school and no adverse effects. ATX was chosen as an initial intervention for George because it offered the possibility of addressing his severe problems in sleep as well as his very problematic oppositional behaviour and inattention using a single agent with relatively smooth coverage throughout the day.

ATX was quite helpful for George, but the teacher's reports of continuing inattention symptoms that were interfering with leaning highlighted the need for further intervention. A higher dose of ATX was not tried because a dose response study of ATX (Michelson et a!. 2001) did not show added benefit to doses above 1.2 mg/kg/day. At this point, the combination of ATX and stimulant every morning was tried. Splitting the dose of ATX provided a way to retain benefits of the stimulant while sustaining improved sleep.