Sleep and Tolerability Study: Comparing the Effects of Adderall XR and Focalin XR

Seattle Children's Healthcare System

Status and phase: Completed; Phase 3

Conditions: Attention Deficit Hyperactivity Disorder

Treatments: Drug: Mixed Amphetamine Salts, ER; Drug: Dexmethylphenidate; Drug: placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00393042

CRIT124E US15

2006-04

2006-0423

Details and patient eligibility

About

The purpose of this study is to evaluate how children and adolescents with Attention Deficit/ Hyperactivity Disorder (ADHD) respond to treatment with three differing doses of stimulant medications used to treat ADHD, Adderall XR® and Focalin XR®. Another purpose of the study is to evaluate if there are differences in sleep and other side effects, such as changes in mood or loss of appetite, which can occur with stimulant medications. A third purpose is to determine if there are differences in the characteristics of individuals who respond better to either of the medications.

This research is being done because the investigators do not know if one of these two commonly used treatments is better tolerated than the other. Children and adolescents with ADHD often have a hard time sitting still, playing quietly, finishing things they start, paying attention, waiting their turn, and not distracting others. These medications improve these symptoms, but sometimes affect sleep, appetite, or mood.

It is hypothesized that at effective and frequently prescribed doses, Adderall will be associated with insomnia, more stimulant side effects, and decreased tolerability during an acute trial relative to Focalin.

Full description

ADHD is often treated with stimulant medications, which have demonstrated short-term efficacy in numerous trials. However, treatment is often discontinued prematurely. Although ADHD often persists through adolescence, approximately half of all children who are treated with a stimulant medication discontinue treatment within one year (Charach, Ickowicz et al. 2004). Presumably, tolerability and treatment compliance are highly related to the side effect profile of stimulant medications (Schachar, Jadad et al. 2002). Sleep problems, particularly insomnia, are frequently associated with ADHD and are often exacerbated by stimulant medications, particularly at higher doses. Other frequent stimulant side effects are decreased appetite and mood lability (dysphoria/euphoria). Little is known about the relative effects of different stimulant formulations and dosages (i.e amphetamine, methylphenidate, dexmethylphenidate) on sleep and tolerability. There is some preliminary data with short acting stimulants suggesting a higher prevalence of sleep and appetite problems with amphetamine relative to mph (Pelham, Aronoff et al. 1999). Several studies indicate that sleep and other stimulant side effects are dose related (Stein, Sarampote et al. 2003), although this has not been found in all studies. Moreover, it is unclear if there are differences between long-acting amphetamine and methylphenidate based stimulants in their side effect profile and tolerability. Thus, we will directly compare these two long acting stimulant medications on their side effect profile and tolerability, including measures of sleep, mood, and evening behavior (e.g., family conflicts). The recently developed extended release formulation of dexmethylphenidate will be compared to one of the most common treatments for ADHD, extended release formulation of mixed amphetamine salts. The subject population will be older children and adolescents (10-17) with ADHD who are most likely to be treated with moderate to higher dose levels of stimulant medications and can complete all self-report measures.

Enrollment: 77 patients

Sex: All

Ages: 9 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Any ADHD subtype, determined by KSADS interview (Kaufman, Birmaher et al. 1997). Comorbidity will likewise be allowed, to ensure representation.
• Signed informed consent and assent
• Clinical Global Impressions - Severity for ADHD (CGI-S-ADHD) rating is greater than or equal to 4
• Findings on physical exam, laboratory studies, vital signs, and ECG are judged to be normal for age
• Pulse and blood pressure are within 95% of age and gender mean
• Able to complete study instruments and swallow capsules
• Willing to commit to the entire visit schedule for the study, including at least one visit to UIC Medical Center.

Exclusion criteria

• Previous diagnosis of mental retardation
• Non-responder to either medication at the doses offered in the study in an adequate trial
• Must not have experienced disabling adverse effects with either medication
• Concomitant psychotropic medications are required or medications which might have a CNS effect
• Any other medical condition which represents a contraindication for either treatment is present
• History of alcohol or drug abuse in the past 3 months, or a positive urinary toxic screen on initial evaluation that is not explained by a time-limited medical circumstance
• Females of childbearing age who are sexually active, do not use acceptable birth control (double protection method), and after counseling, are unwilling to do so
• History of allergic reactions to multiple medications
• A history of psychosis
• Diagnosis of bipolar disorder

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

77 participants in 2 patient groups

Focalin XR then Adderall XR

Experimental group

Description:

Subjects are given the Focalin XR first (dexmethylphenidate) for four weeks with a randomized placebo week followed by Adderall XR (mixed amphetamine salts) for four weeks with a randomized placebo week.

Treatment:

Drug: Dexmethylphenidate

Drug: Mixed Amphetamine Salts, ER

Drug: placebo

Adderall XR then Focalin XR

Experimental group

Description:

Subjects are given the Adderall XR (mixed amphetamine salts) for four weeks with a randomized placebo week followed by Focalin XR first (dexmethylphenidate) for four weeks with a randomized placebo week.

Treatment:

Drug: Dexmethylphenidate

Drug: Mixed Amphetamine Salts, ER

Drug: placebo