Optimising Attention-deficit–Hyperactivity Disorder Therapy – Efficacy and Tolerability of Equasym XL Modified-release Capsules
Optimising Attention-deficit–Hyperactivity Disorder Therapy – Efficacy and Tolerability of Equasym XL Modified-release Capsules
European Psychiatric Review 2008;1(1):56-7
Attention-deficit–hyperactivity disorder (ADHD) is one of the most commonly diagnosed behavioural disorders during childhood, occurring in about 4% of all school-age children. Fortunately, in recent years ADHD management has improved considerably. For treatment, several novel second-generation, once-daily methylphenidate formulations are currently available, aiming at easing symptom control, especially during school hours, and enhancing compliance by lower dosing intervals. These new formulations are as efficient as immediate-release (IR) methylphenidate drugs, which have to be administered at least twice a day.1 The outstanding feature of these novel formulations is their combination of an IR and an extended-release (ER) compound. In the case of Equasym XL, 30% of the total dose guarantees fast relief in the morning and 70% provides a long-lasting effect until the afternoon. The efficacy of this new product, which was especially developed for the daily routine of elementary-school children and high-school students, has been confirmed in various studies.
Compliance and Its Impact – No Need for Drugs That Are Not Taken
When psychosocial measures alone are insufficient, methylphenidate is one of the drugs of first choice for symptomatic treatment of patients with ADHD. As with all drugs, however, compliance increases with fewer administrations. In addition, children in particular often feel embarrassed to take prescription drugs in the presence of other children; herefore, they prefer to skip their medication rather than being teased. Thus, a once-daily drug administration before going to school is considered a great advantage by the afflicted and their parents. Without endangering immediate symptom control, this goal was achieved by combining IR with ER methylphenidate in one drug. While the IR compound of the drug is responsible for a fast effect – which, however, is of only short duration – the ER ingredient leads to a lasting effect throughout the afternoon for sustained relief of symptoms. Today, several second-generation methylphenidate formulations given only once a day are available either as capsules, such as Equasym XL, or as tablets, aiming at easing symptom control, especially during school hours, and enhancing compliance by lower dosing intervals. However, these once-daily formulations use different delivery systems, resulting in different pharmacokinetic profiles.2
Optimal Immediate-/Extended-release Ratio for a Quick and Lasting Effect
Before Equasym XL was put on the market, the optimal dose ratio for a controlled-delivery formulation of methylphenidate was investigated. Studies were performed in healthy adults as well as in children with ADHD, investigating 20:80, 30:70 and 40:60 IR/ER prototype formulations. Efficacy measures included the Swanson, Kotkin, Atkins, M/Flynn, Pelham (SKAMP) scale and the 10-minute permanent products measure of performance (PERMP) test.3 Pharmacokinetic analyses in the healthy volunteers revealed that all three formulations led to biphasic methylphenidate plasma concentrations with initial peaks approximately 1.5 hours after drug intake and another peak five to eight hours thereafter; however, the magnitude differed for the various agents. Since the 30:70 and 40:60 formulations were more comparable to twice-daily IR methylphenidate (Ritalin®), these agents were further investigated in children with ADHD. Both formulations given once a day in the mornings were effective in controlling ADHD symptoms and were superior to placebo treatment in the primary efficacy measures. They both had promising profiles, yet the 30:70 formulation was preferred and chosen for commercial development due to its more consistent treatment effect over the entire study observation period3 and its superiority during morning hours, a time particularly important to children, who have to give their best in school.
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