my personal edition > psychiatry other > news


  E-Mail this DGNews to a colleague

DGNews

Study Suggests Atomoxetine Significantly Improved Functioning in Children With Both ADHD and Anxiety Disorders

TORONTO, CANADA -- May 31, 2006 -- Data from a recent clinical study suggests that Strattera® (atomoxetine) significantly improved measures of psychosocial functioning (the impact of ADHD on various aspects of your life such as quality of relationships with family and peers) in children and adolescents who also had anxiety disorders.

The results of the 12-week study were presented today at the 159^th annual meeting of the American Psychiatric Association (APA).

The functioning assessment was part of a larger trial, of which the primary endpoint was to examine Strattera's ability to treat ADHD in children and adolescents with ADHD and anxiety disorders.

At the end of the study, Strattera significantly reduced ADHD symptoms such as inattention, hyperactivity and impulsivity by 39%, compared to a 4% improvement in patients taking placebo. Strattera also significantly reduced anxiety symptoms like excessive worry, sweating and trembling by 32%, compared with 19% of patients taking placebo.

The secondary analysis examined Strattera's effect on patient functioning. At the end of the study, patients taking Strattera saw a significant improvement in functioning compared to placebo as measured on the following scales, Multidimensional Anxiety Scale for Children (MASC), 9% improvement for Strattera versus 4% worsening for placebo; Life Participation Scale for ADHD-Revised (LPS-ADHD-R), 31% improvement for Strattera versus 10% improvement for placebo and the Child Health Questionnaire-Parent Completed Full Length (CHQ-PF50) 23% improvement for Strattera versus 11% improvement for placebo.

"It can be difficult to treat ADHD in children because of the complex nature of the disorder and the presence of underlying issues such as anxiety," said Dr. Umesh Jain, Head, Canadian ADHD Resource Alliance (CADDRA). "In some patients where anxiety is present, it is important to treat the anxiety, as well as the ADHD symptoms."

At least 25% of children with ADHD also suffer from anxiety disorders1 like separation anxiety, generalized anxiety or social phobia. 2 If left untreated, research has shown that anxiety disorders can contribute to difficulties in school, impaired relations with other children, low self-esteem, alcohol or other substance abuse, problems at work, and anxiety disorders in adulthood.3

Study Highlights:
- At the 12-week study endpoint, the response rate for improvement in ADHD symptoms for eligible patients, was significantly higher for Strattera relative to placebo (hyperactivity / impulsivity: -4.5 vs. -0.8; inattention: -4.6 vs. 0.1 on the ADHD Rating Scale-IV-Parent Version (ADHDRS-IV-PI)
- Mean change from baseline also showed greater improvement for Strattera-treated patients than those taking placebo (decreases of 10.5 points vs. 1.4 respectively, or 39% vs. 4%)
- Strattera patients also experienced significantly greater improvement in anxiety symptoms on the Pediatric Anxiety Rating Scale (PARS) compared with placebo (decreases of 5.5 points vs. 3.2 respectively, or 32% vs. 19%)
- Secondary analyses also showed significant improvement in anxiety (a decrease of -4.6 vs. an increase of 2.1 on the Multidimensional Anxiety Scale for Children. (MASC))
- In this study, the most common adverse events (occurred at a rate of ≥ 5% and at least twice the rate of placebo) were decreased appetite, upper abdominal pain, vomiting, nausea and influenza
- There were no clinically significant baseline-to-endpoint treatment differences in electrocardiogram (ECG) or laboratory measures, nor were there significant differences in the incidence of clinically important or treatment-emergent abnormal ECG or laboratory measures.

Methods
In this 12-week randomized, double-blind, placebo-controlled study, 87 patients who met the DSM-IV criteria for ADHD and either separation anxiety, generalized anxiety or social phobia received Strattera (dosage increased from 0.8 mg/kg/day to a target dose of approximately 1.2 mg/kg/day and not exceeding 120 mg/day). This was compared to an untreated control group of 89 patients on placebo. A total of 66 patients in each group completed the study.

In the study, that comprised six visits over approximately 12 weeks, patients were assessed according to the 18-item ADHDRS-IV-PI scale and total patient- and parent-reported PARS score. The secondary analysis examined patient functioning on the Multidimensional Anxiety Scale for Children (MASC), Life Participation Scale for ADHD-Revised (LPS-ADHD-R), and the Child Health Questionnaire-Parent Completed Full Length (CHQ-PF50) scales. This study was designed to examine Strattera's ability to improve symptoms of ADHD and comorbid anxiety in children with both ADHD and anxiety. It was not designed to study the effects of Strattera on ADHD or anxiety alone.

Sample sizes in this study were not sufficient to detect uncommon safety differences between treatments. Because of the 12-week duration, long term efficacy and safety conclusions cannot be drawn from this data.

Additionally, generalizability is limited since the patients in this study were clinically referred, and results do not indicate whether Strattera is independently beneficial for treatment of any single anxiety disorder.

About ADHD
ADHD is a complex disorder that can be difficult to diagnose and often occurs in tandem with other psychiatric diagnoses like anxiety or depression.4,5 Therefore, proper diagnosis of all of a patient's symptoms is vital for choosing appropriate treatment and monitoring for both safety and efficacy. ADHD can have lifelong consequences, including poor peer relations, poor academic performance, lower job status, and increased risk-taking behaviours such as substance abuse.5

About Strattera
Strattera, a selective norepinephrine reuptake inhibitor, is the first Health Canada approved non-stimulant to treat ADHD and provide full-symptom relief. It is approved for the treatment of ADHD in children six years of age and over, adolescents, and

adults.6 It is not known precisely how Strattera reduces ADHD symptoms, but scientists believe it works by blocking or slowing reabsorption of norepinephrine, a chemical in the brain considered important in regulating attention, impulsivity, and activity levels.7 This keeps more norepinephrine at work in the spaces between neurons in the brain. Improved efficiency in the norepinephrine system is associated with improvement in symptoms of ADHD.7

Since its first approval in the United States in 2002, more than 3.7 million patients have taken Strattera worldwide. It has been studied in more than six thousand patients in clinical trials, some for as long as three years. In 2004, Strattera was approved in Canada.

Strattera has been found to be generally safe and well tolerated.8 The most commonly observed adverse events in placebo-controlled clinical trials in children and adolescents were upset stomach, decreased appetite, nausea, vomiting, dizziness, tiredness, sleepiness and irritability.6

Strattera has a gradual onset of action, and the dose needs to be increased slowly to reach an effective maintenance dose as directed by a health care professional. Patients should be maintained at each dose level for at least 10 days to determine if the dose is effective. The dose should then be increased to the next level for patients who have not achieved optimal clinical response. It is important that patients do not exceed the recommended initial dose, subsequent dose increases and maximum daily dose. If the dose of Strattera is increased too quickly, there may be increased side effects, such as sleepiness and digestive system complaints. Improvement of ADHD symptoms is generally observed within one to four weeks after starting therapy.6

In some children and teens, Strattera increases the risk of suicidal thoughts. A combined analysis of 12 studies of Strattera showed that in children and teens this risk was 0.4% for those taking Strattera compared to none for those on placebo. A similar analysis in adults treated with Strattera did not reveal an increased risk of suicidal thoughts. Parents should call their doctor right away if their child has thoughts of suicide or sudden changes in mood or behaviour, especially at the beginning of treatment or after a change in dose.6

Strattera should not be taken at the same time as, or within two weeks of taking, a monoamine oxidase inhibitor (MAOI) or by patients with narrow angle glaucoma. Patients with symptoms of heart disease, moderate to severe hypertension, advanced atherosclerosis or uncontrolled hyperthyroidism should not take Strattera. As with all agents with sympathomimetic effects, caution is advised in patients who are involved in strenuous activity, use stimulants, or have a family history of sudden death or death due to heart problems. Patients with a history of high or low blood pressure, increased heart rate, or any heart or blood vessel disease should tell their doctor before taking Strattera.6

Use of drugs for treatment of ADHD has been associated with sudden death in children with pre-existing heart conditions.9

Although Strattera is not a stimulant, its use should generally be avoided in people with structural heart abnormalities. 6

Strattera has not been tested in children less than six years of age or in geriatric patients.

As with all ADHD medications, growth should be monitored during treatment although height and weight data measured for up to two years indicates minimal, if any, long-term effects. Strattera can cause liver damage in rare cases.

Patients should tell their doctor right away if they have itching, dark urine, yellow skin/eyes, upper right-sided abdominal tenderness, or unexplained "flu-like" symptoms.6


REFERENCES:
1. Diagnosis of attention-deficit/hyperactivity disorder. Summary, technical review: Number 3, August 1999. Agency for Health Care Policy and Research, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/adhdsutr.htm. Current as of October 1999; Accessed May 2006.
2. Atomoxetine Treatment for Pediatric Patients with Attention-Deficit/Hyperactivity Disorder and Comorbid Anxiety, American Psychiatric Association Meeting, 2006.
3. Substance Abuse and Mental Health Service Administration (SAHMSA), "Children and Adolescents with Anxiety Disorders." Accessed online at http://www.mentalhealth.samhsa.gov/publications/allpubs/CA-0007/default.asp on April 3, 2006.
4. American Academy of Pediatrics. Clinical practice guideline: Diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics 2000;105:1158-1170.
5. Karande S. Attention deficit hyperactivity disorder: A review for family physicians. Indian J Med Sci 2005;59:547-556.
6. Strattera® Product Monograph. Eli Lilly Canada Inc. March 22, 2006.
7. Caballero J, Nahata MC. Atomoxetine hydrochloride for the treatment of attention-deficit/hyperactivity disorder. Clin Ther 2003;25:3065-3083.
8. Barton J. Atomoxetine: a new pharmacotherapeutic approach in the management of attention deficit/hyperactivity disorder. Arch Dis Child 2005;90:26-29.
9. Nissen SE. ADHD drugs and cardiovascular risk. N Engl J Med 2006;354:1445-1448.


SOURCE: Eli Lilly and Company

E-Mail this DGNews to a colleague

To print, use this version