Health-Related Quality of Life and Functional Outcomes from a Randomized-Withdrawal Study of Long-Term Lisdexamfetamine Dimesylate Treatment in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Abstract

BackgroundThe stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD.ObjectiveSecondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.MethodsPatients aged 6–17 years with diagnosed ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons.ResultsThe open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one standard deviation below the normative mean in four of the five domains, and there was significant improvement across all domains from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean CHIP-CE: PRF T-scores deteriorated in all domains in the placebo group, but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Risk Avoidance (effect size 0.829; p < 0.001), Achievement (0.696; p < 0.001) and Satisfaction (0.636; p < 0.001) domains. Mean pretreatment WFIRS-P scores were lowest in the Family domain and the Learning and School domain. WFIRS-P total score and scores in all domains improved significantly from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean scores deteriorated in the placebo group but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Family, Learning and School, and Risky Activities domains and in total (effect size 0.908; p < 0.001).ConclusionsUsing parent-rate...

Lisdexamfetamine Dimesylate (Vyvanse) for the Treatment of Neurogenic Anejaculation

“…Lisdexamfetamine dimesylate (Vyvanse) is a medication commonly prescribed to children and adolescents with attention deficit hyperactivity disorder. Lisdexamfetamine dimesylate is a prodrug that is converted by the liver to the active dextroamphetamine (a noncatecholamine, sympathomimetic amine), which causes release of dopamine and norepinephrine from the presynaptic nerve terminals and blocks catecholamine re-uptake by competitive inhibition (Banaschewski et al, 2014). In theory, this release of dopamine and norepinephrine should potentiate the sympathetic receptors mediating seminal emission.…”

“…In theory, this release of dopamine and norepinephrine should potentiate the sympathetic receptors mediating seminal emission. The drug is generally well tolerated with a minimal side effect profile, and its treatment effectiveness for attention deficit hyperactivity disorder and tolerability has been validated in double blinded, placebo-controlled studies (Banaschewski et al, 2014).…”

Actualización en el tratamiento farmacológico del trastorno por déficit de atención/hiperactividad: lisdexanfetamina y guanfacina de liberación retardada

“…Debido a las diferencias de la LDX con el MPH, no se puede ajustar la LDX en base a las dosis previas que el paciente tomaba de este último. El tratamiento siempre ha de iniciarse con dosis bajas (generalmente 30 mg) y ajustarse de forma progresiva, según tolerabilidad y eficacia, hasta un máximo de 70 mg. La eficacia de la LDX como tratamiento del TDAH ha sido bien establecida en múltiples estudios, en niños, adolescentes y adultos, tanto en estudios de registro y mantenimiento estadounidenses como europeos [7,[14][15][16][17][18][19][20][21]. También se ha comprobado la eficacia de la LDX en pacientes tratados previamente con MPH y cuya respuesta no fue adecuada, medida cuantitativamente -menos de un 30% de reducción en la ADHD Rating Scale (ADHD-RS)-, con una respuesta clínica adecuada en casi el 80% de los pacientes, que en numerosas ocasiones se acompañó de una mejoría en la manifestación de los sentimientos medida a través de la escala de expresión emocional para niños [22,23].…”

“…Por ejemplo, en el estudio de registro europeo, el porcentaje de pacientes que refirieron 'mejorar' , según la escala de impresión clínica global, fue del 78% frente a un 61% en el grupo de MPH OROS y un 14% en el grupo con placebo; las diferencias fueron significativas entre ambos grupos de tratamiento activo y placebo [16]. Cuando se suspendió el tratamiento con LDX, las diferencias entre el grupo placebo y el que continuó con tratamiento fueron aún mayores [21]. Se obtuvieron diferencias significativas en una escala de calidad de vida para padres (Child Health and Illness Profile-Child Edition: Parent Report Form) en logros, evitación de riesgos, resistencia, satisfacción y global.…”

“…Se obtuvieron diferencias significativas en una escala de calidad de vida para padres (Child Health and Illness Profile-Child Edition: Parent Report Form) en logros, evitación de riesgos, resistencia, satisfacción y global. Durante la suspensión del tratamiento, las diferencias entre el grupo placebo y el que mantuvo el tratamiento en la WFIRS-P se produjeron en todos los dominios, pero sobre todo en los que afectan a la familia, el aprendizaje y la escuela, las actividades sociales y las actividades de riesgo, donde las mejorías se observaron desde la fase II del estudio [7,16,21,35]. Del mismo modo, la LDX se ha demostrado más eficaz en la mejoría de la puntuación total de la WFIRS-P cuando se compara con la ATX [36].…”