This is the first of a two-part edition of Med Check, featuring new
research abstracts presented at APA's 157th Annual Meeting in New York City in
May. This part covers research relating to medication treatment of ADHD,
Alzheimer's disease and other dementias, and bipolar disorder. The second part
will cover pharmacotherapy of depression and anxiety, psychotic disorders, and
The research presented in this format is preliminary, has not been
published in a peer-reviewed journal, and may involve uses of medications for
purposes that are not FDA approved. New research abstract reports are largely
sponsored by the products' manufacturers.
• Atomoxetine is associated with fewer sleep
disturbances than methylphenidate in children with ADHD. A Lilly-funded,
double-blind, randomized study looked at 85 patients taking the two drugs over
16 weeks in a crossover design. Patients took either atomoxetine or
methylphenidate for seven weeks, followed by a 10- to 20-day drug-free phase.
Then patients crossed over to the opposite drug for seven weeks. Sleep
assessments included actigraphy, polysomnography (on a subset of patients),
and parent and child diaries.
Patients taking atomoxetine experienced shorter time to sleep onset, longer
actual sleep time, and fewer sleep-related problems. Results were consistent
across the different measures.
APA: NR496. Presented May 4, 2004.
• Atomoxetine is effective in improving ADHD symptoms
in a real-world setting, according to data from the first prospective,
observational, longitudinal, open-label study of the drug's effects. Data were
collected on 482 pediatric patients during routine physician visits; drug
administration and dosing were at the physician's discretion. Using the
Physician Global Impression: ADHD Severity scale as well as parent rating
reports, researchers found that atomoxetine improved ADHD symptoms throughout
the day and into the evening for many patients. Improvement was observed in
core symptoms, overall behavioral assessment, and family interactions and was
consistent between patients who had never taken ADHD medication prior to the
study and those who had previously taken stimulants.
APA: NR475. Presented May 4, 2004.
• Mixed amphetamine salts—extended release is
associated with significantly greater improvement in school performance in
children aged 6 to 12, compared with atomoxetine. In a large, Shire-funded,
classroom-based study, children taking either medication improved on measures
of behavior, attention, and academic productivity. However, those taking mixed
amphetamine salts—extended release consistently showed greater
improvement in all three areas, compared with those on atomoxetine throughout
a 10- to 12-hour classroom day. Side effects were mild to moderate and
consistent with those known with the two medications.
APA: NR450. Presented May 4, 2004.
• OROS methylphenidate may provide better symptom
relief than atomoxetine, according to data from a
McNeil-funded study of more than 1,300 children between the ages of 6 and 12.
Preliminary results for the first half of patients completing the three-week,
open-label, parallel-design study showed an early and consistent advantage for
those taking OROS methylphenidate. Based on ratings with the
Attention-Deficit/Hyperactivity Disorder Rating Scale, patients taking OROS
methylphenidate improved by 11.5 points by the end of the first week, while
those taking atomoxetine, on average, improved 8.5 points.
By the end of the third week, patients taking OROS methylphenidate had an
average score reduction of 21.1 points, compared with 15.9 points for those
taking atomoxetine. Treatment-emergent adverse effects were similar in both
groups and consistent with the two medications' experience. APA: NR451.
Presented May 4, 2004.
• Memantine is safe and well tolerated in both
short-term and long-term treatment of dementia, according to a pooled analysis
of 940 patients treated with the NMDA receptor antagonist, compared with 922
patients treated with placebo.
In short-term trials (fewer than 28 weeks) only headache and confusion were
reported in more than 5 percent of patients taking memantine and at a rate at
least twice that of placebo. Agitation, diarrhea, accidental injury, and
urinary incontinence were reported in more than 5 percent of patients taking
memantine; however, these rates were significantly lower than those of the
corresponding placebo groups. In longer-term extension trials (up to two
years) agitation and urinary tract infection were the most frequently reported
adverse events, though rates were indistinguishable between those of memantine
and placebo. APA: NR831. Presented May 6, 2004.
• Rivastigmine appears to slow the progression of
Alzheimer's disease for as long as five years. Pooled long-term data from
studies evaluating more than 2,000 patients on the acetylcholinesterase
inhibitor for more than five years demonstrate a significant decrease in the
rate of decline, compared with projected declines in cognitive domains if the
same patients had not been on medication. Using the Alzheimer's Disease
Assessment Scale (ADAS-cog) patients at the beginning of their five years of
rivastigmine therapy had an average score of 17.4. By the end of the study,
those patients had, on average, declined to an average score of 36.8 (higher
numbers indicate more cognitive dysfunction). In comparison, those same
patients would have been projected to decline to an average score of 56.9 if
they had not taken any medication. Overall, rivastigmine was associated with
delaying a patient's decline into severe dementia by at least two years.
APA: NR501. Presented May 4, 2004.
• Aripiprazole is safe and effective in the treatment
of patients with acute manic and mixed episodes associated with bipolar
disorder. A phase III, multicenter, double-blind, placebo-controlled study
evaluated a 30 mg dose over a three-week period in 272 patients with bipolar I
disorder. By day four, patients taking aripiprazole had an average 12.5 point
improvement on the Young Mania Rating Scale, compared with a 7.2 point
improvement for those taking placebo. Adverse effects seen in the aripiprazole
group at a rate of at least 10 percent and twice that seen in the placebo
group included stomach upset, constipation, akathisia, and pain in the
A second analysis pooled data from four separate multicenter trials
comparing aripiprazole with placebo in nearly 1,000 patients. In this
analysis, there was no statistically significant weight gain seen with
aripiprazole, compared with placebo, and no dose-dependent differences in
extrapyramidal adverse events. The most frequently reported adverse events
were headache, nausea, dyspepsia, agitation, and akathisia.
APA: NR742, NR746. Presented May 5, 2004.
• Quetiapine is safe and effective for the treatment
of patients experiencing acute manic episodes associated with bipolar I
disorder. Remission rates were compared after three weeks and at the end of a
12-week, double-blind, placebo-controlled study, with remission defined as a
Young Mania Rating Scale score of 12 or less. For patients taking quetiapine,
37.5 percent achieved remission by day 21 and 65.4 percent by day 84. In
comparison, only 23 percent of those taking placebo achieved remission by day
21 and 35.9 percent did so by day 84. The most frequently encountered adverse
events noted with quetiapine are somnolence, dry mouth, dizziness,
constipation, asthenia, abdominal pain, changes in liver function, and weight
gain. APA: NR 752. Presented May 5, 2004.
• Ziprasidone provides rapid and significant
improvement in patients with acute bipolar mania. A pooled analysis of two
randomized, double-blind studies involving 415 patients hospitalized for acute
mania showed that improvement was evident as early as the second day, and
consistent improvement continued over the course of the three-week
Ziprasidone was equally effective in patients with manic or mixed episodes
and in those with or without psychotic symptoms. Dosing started at 80 mg per
day and was titrated up to 160 mg per day by the second or third treatment
day. The most common side effects were somnolence, headache, and
In a second study—a one-year, open-label, extension
study—ziprasidone continued to improve manic symptoms, with no increases
in weight, cholesterol, or triglycerides. APA: NR777, NR745. Presented May