Strattera Treatment in Children With ADHD Who Have Poor Response to Stimulant Therapy

Strattera (atomoxetine) is a non-stimulant presynaptic norepinephrine reuptake inhibitor recently approved by the Food and Drug Administration for use in child, adolescent and adult patients with ADHD. Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors. Thus, Strattera could be a viable alternative treatment for ADHD individuals who do not respond to stimulants.

The purpose of this study is to assess the effectiveness, safety and tolerability of Strattera in youth, ages 6-17 years with ADHD who failed to respond to an adequate trial of stimulant treatment. If this initial study shows proof of the concept, we will follow-up the study with a randomized clinical trial.

Inclusion criteria

• Male and female outpatients 6-17 years of age.
• Subjects with the diagnosis of attention deficit hyperactivity disorder (ADHD), by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), as manifested in clinical evaluation and confirmed by structured interview.
• ADHD rating scale-symptom checklist > 24
• Subjects with a past history of depression, bipolar disorder, anxiety disorder (including obsessive compulsive disorder [OCD]) without current disorder for > 3 months as ascertained through structured diagnostic interview and clinical exam.
• Subjects treated for anxiety disorders and depression (with non-MAOI antidepressants [e.g., SSRIs, bupropion, venlafaxine] or benzodiazepines) who are on a stable medication regimen for at least three months, and who have a disorder specific Clinical Global Impression (CGI)-severity score ≤ 3 (mildly ill) and who have a score on the Hamilton-Depression and Hamilton-Anxiety Rating Scale below 15 (mild range) will be included in the study.
• Subjects with a past or present history of tics will be eligible.
• Subjects with a past history of substance use disorders but drug and alcohol free for > 6 months.
• Subjects with mild cases of asthma and allergy will be included.
• Potential subjects will have failed an adequate trial of a stimulant as defined by:

• Subjects who had intolerable side effects on a stimulant, or
• Poor response (an ADHD CGI-I of > 3) on at least 4 weeks of > 1.0 mg/kg/day of a methylphenidate product; or > 0.5 mg/kg/day of an amphetamine product.
• Only English-speaking subjects will be allowed into the study for the following reasons:

• the assessment instruments are not available and have not been adequately standardized in other languages;
• the clinical trials facility is located in Cambridge and not in the Massachusetts General Hospital (MGH) main campus without the availability of translators;
• psychiatric questionnaires and evaluations are taxing and adding the complexity of a translator has the potential to make the patient experience even more exhausting.

Exclusion criteria

• Any clinically unstable psychiatric conditions including the following:

• acute psychosis,
• acute panic,
• acute OCD,
• acute mania,
• acute suicidality,
• acute substance use disorders (alcohol or drugs),
• sociopathy,
• criminality.
• Any metabolic, neurological, hepatic, renal, cardiovascular, hematological, ophthalmic, or endocrine disease.
• Clinically significant abnormal baseline laboratory values which include the following:

• Values which deviate greater than 20% from the normal ranges of the laboratory standard for a basic metabolic screen and complete blood count.
• Exclusionary blood pressure parameters will include any values above 140 (systolic) and 90 (diastolic).
• Exclusionary electrocardiogram (ECG) parameters will include a QTC > 460 msec, QRS >120 msec, and PR > 200 msec. Subjects having ECG evidence of ischemia or arrhythmia as reviewed by an independent cardiologist.
• Mental retardation (intelligence quotient [I.Q.] < 75).
• Organic brain disorders.
• Seizures.
• Pregnant or nursing females.
• Subjects with current adequate treatment for ADHD or a history of a previous adequate trial of Strattera.
• Prior hypersensitivity to atomoxetine.
• MAOI antidepressant use currently or within two weeks of starting study.
• Urinary retention or bladder dysfunction.
• Narrow angle glaucoma.