Remission versus response as the goal of therapy in ADHD: a new standard for the field?

Attention-deficit/hyperactivity disorder (ADHD) has a substantial negative impact; however, within long-term follow-up studies, a proportion of patients do very well, both symptomatically and functionally, suggesting that the lower the symptom burden, the greater the functional improvements. Studies in major depressive disorder have identified a relationship between symptomatic remission and restoration of normal functioning.

The purpose of this article was to propose a definition of remission in ADHD, review remission rates in clinical trials for commonly used medications, and explore the relationship between symptomatic remission and optimal functioning.

Remission and response rates for medications were obtained through MEDLINE searches of English-language citations (1999-2005) and meeting abstracts (2003-2005) using the terms amphetamine, atomoxetine, methylphenidate, ADHD, efficacy, effectiveness, and controlled trial, as well as hand searches of efficacy studies. Evidence from randomized controlled trials, as well as effectiveness studies, where the proportions of patients achieving predefined cutoff points for remission or response are reported, was reviewed. Because higher remission rates were identified with the oral, osmotic, controlled-release system (OROS) of methylphenidate, a relationship between symptomatic response/remission and optimal functioning was explored further.

Remission in ADHD should be defined as a loss of diagnostic status, minimal or no symptoms, and optimal functioning when individuals are being treated with or without medication. Symptomatic remission can be operationalized as a mean total score of S1 on most standardized questionnaires. For the medications examined (OROS methylphenidate, immediate-release methylphenidate, atomoxetine, and mixed amphetamine salts), response rates were comparable at approximately 70% to 75%; however, remission rates were higher with OROS methylphenidate compared with either immediate-release methylphenidate or atomoxetine (remission rates with amphetamines were not found). Benefits, including decreased illness burden as well as improved psychosocial and academic functioning, were associated with treatment versus no treatment and were greater with medication that offered higher remission rates.

The literature provided evidence that greater symptom improvements are associated with greater functional improvements, emphasizing that remission of ADHD as defined should be the goal of therapy. Treatment ought to include the early use of strategies with the greatest chance of achieving remission. Future clinical research should use remission as the primary outcome.