Med Check

Atomoxetine significantly reduces core symptoms in children with ADHD for as long as 24 hours compared with placebo, reported Humberto Quintana, M.D., of Louisiana State University, and colleagues. In a secondary analysis, the team found some differences in the drug's effects when given once daily in the morning compared with once daily in the evening.

The results are from a randomized, double-blind, placebo-controlled trial that involved 288 children with ADHD. The six-week study compared a group who took atomoxetine in the morning with a group who took the drug in the evening, and compared both groups with a placebo-control group. Children in both drug-dosing schedules did statistically significantly better than those on placebo.

The group on the morning dose did better than the group on the evening dose as measured by the ADHD Rating Scale, the hyperactive/impulsive subscale of the ADHD-RS, and on Clinical Global Impression–Severity Scale. In addition, the children on the evening dose were more likely to experience an adverse event than the children on the morning dose. However, no differences were seen in the two groups in terms of the children's behavior in the morning and in the evening as assessed by their parents. Further, both groups displayed clinically significant improvement 24 hours after receiving a dose.

The most common adverse events noted in those taking atomoxetine were abdominal pain, decreased appetite, vomiting, headache, somnolence, and nausea.

APA 2005: NR 467 & NR 469; Funding: Eli Lilly and Co.

Modafinil, in a once-daily pediatric formulation, was found to be both safe and effective in children with ADHD aged 6 to 17 in terms of improving behavior and lessening the severity of symptoms associated with ADHD, reported Laurence Greenhill, M.D., of the New York State Psychiatric Institute, and colleagues.

For the nine-week study, 163 patients were randomly assigned to either modafinil or placebo. Modafinil was associated with robust improvement (effect size 0.69) in ADHD symptoms measured on the ADHD Rating Scale, the Connors' Parent-Rating Scale, and the clinician-rated Clinical Global Impression–Improvement (CGI-I) subscale. Modafinil was associated with significant improvements in overall condition (CGI-I score of 1 or 2) in 48 percent of patients, compared with 17 percent for those taking placebo.

The most common adverse events in patients taking modafinil were insomnia (29 percent compared with 4 percent in placebo), headache (20 percent vs. 15 percent), and decreased appetite (16 percent vs. 4 percent). Similar results were reported by James Swanson, M.D., of the University of California-Irvine, and colleagues, in a trial using the same protocol involving 128 patients. Effect size in the second study was 0.64 for modafinil.

APA 2005: Scientific & Clinical Report Session 4, No. 13, and Session 16, No.47; Funding: Cephalon

Intramuscular aripiprazole appears to be as effective as lorazepam at reducing agitation in patients with bipolar I disorder with either mixed or manic episodes, reported Dan Oren, M.D., of Bristol-Myers Squibb Co. and colleagues at BMS and Otsuka Pharmaceuticals. In a randomized, double-blind trial, 301 voluntarily hospitalized patients with acute agitation associated with bipolar disorder were administered either placebo, 10 mg IM aripiprazole, 15 mg IM aripiprazole, or 2 mg IM lorazepam.

Two hours after injection, patients who received 10 mg aripiprazole saw a mean improvement of 8.7 points on the Positive and Negative Syndrome Scale–Excited Component, compared with 8.7 points for those receiving 15 mg aripiprazole, 9.6 points for those receiving 2 mg lorazepam, and 5.8 points for those receiving placebo.

At two hours, 37 percent of those on placebo were classified as responders (CGI-I score of 1 or 2) compared with 69 percent of those receiving 10 mg aripiprazole, 63 percent of those receiving 15 mg aripiprazole, and 69 percent in those receiving lorazepam.

The most common adverse events seen with aripiprazole were nausea, headache, dizziness, and somnolence. The most common adverse events seen with lorazepam were sedation, dizziness, and somnolence.

APA 2005: NR 275; Funding: BMS/Otsuka

Lamotrigine alone may be as effective as lamotrigine combined with other psychotropics in stabilizing patients with bipolar disorder who are in a depressive episode, reported Beth Bentley, Pharm.D., of GlaxoSmithKline.

Data from two eight- to 16-week open-label phases of two long-term lamotrigine maintenance trials were combined. Of the 1,305 patients in the combined trials, 897 had depressive symptoms.

In the first study, 161 patients received lamotrigine as monotherapy. In the second study, 736 patients received lamotrigine plus other psychiatric medications (most commonly antidepressants). Compared with patients who received lamotrigine as adjunctive therapy, patients who entered the clinical trial on no medication and received only lamotrigine experienced statistically significantly greater rates of stabilization and improvement in scores on the Hamilton Rating Scale for Depression. In addition, none of the monotherapy patients exhibited signs of switching to mania.

APA 2005: NR 306; Funding: GSK

Olanzapine/fluoxetine combination (OFC) produced significantly greater improvement in patients with bipolar depression in overall severity of illness, depressive symptoms, and manic symptoms compared with lamotrigine therapy in patients with bipolar depression, reported Paul Keck Jr., M.D., of the University of Cincinnati and colleagues at Eli Lilly.

During the acute phase of a randomized, double-blind comparator study, 410 patients were randomly assigned to either OFC or lamotrigine. The OFC group saw greater improvement on average across the seven-week acute phase of the study (as measured by Clinical Global Impression–Severity scores). In addition, the OFC group had greater improvement on the Montgomery-Asberg Depression Rating Scale, Global Assessment of Function Scale, and Clinical Global Impressions–Improvement Scale.

Significantly more patients treated with OFC reported somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor. Those taking lamotrigine reported significantly higher rates of serious adverse events, such as rash.

APA 2005: NR 376; Funding: Eli Lilly

Olanzapine, quetiapine, and risperidone are not significantly different from one another with respect to patients' self-reported levels of function and overall measures of health-related quality of life, reported Krishnan Ramaswamy, Ph.D., of Janssen Medical Affairs and colleagues.

The researchers used the Short Form-8 Health Survey to measure mental and physical health status, including a wide array of adverse effects, and the Psychological General Well-Being Scale to measure patient functioning. There were 240 subjects (81 taking olanzapine, 95 quetiapine, and 64 risperidone).

Patients taking any of the three experienced sedation and decreased libido at varying rates; however, the differences were not statistically significant. Only two adverse events, insomnia and concentration difficulties, were statistically significantly different between the three drugs. There were no statistically significant differences in overall quality of life or functioning between the three groups of patients.

APA 2005: NR 394; Funding: Janssen Medical Affairs ▪