RESUMEN
Objective: Attention-deficit/hyperactivity disorder (ADHD) is estimated to affect up to 5% of adults worldwide. Preclinical work demonstrates that L-Threonic Acid Magnesium Salt (LTAMS) administration is associated with neurobiological and neurofunctional effects that could offer clinical benefits in ADHD treatment.Methods: Participants were 15 adults with ADHD of moderate severity. Subjects received up to 12 weeks of open-label LTAMS administered as MMFS302 and MMFS202. The study was approved by the Institutional Review Board and posted on ClinicalTrails.Gov (NCT02558790).Results: 47% of subjects met our criteria of response attaining a CGI-Improvement score ≤2 and AISRS total reduction ≥25%. Significant improvement was seen in the AISRS, CGI-I, and the shifting subscale of the BRIEF. Changes in IQ and WASI-II performance were favorable and significant in the study population.Conclusion: LTAMS supplementation was found to be effective and well tolerated. Nearly half of participants met our definition of ADHD symptom clinical response. These results support the need to further evaluate this compound in larger samples under double-blind conditions.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Butiratos/uso terapéutico , Estimulantes del Sistema Nervioso Central , Adulto , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Suplementos Dietéticos , Método Doble Ciego , Humanos , Proyectos Piloto , Resultado del TratamientoRESUMEN
PURPOSE/BACKGROUND: Interventions for attention-deficit/hyperactivity disorder (ADHD) may be inadequate for some patients. There is evidence that supplementation with L-methylfolate augments antidepressant agent effects and thus might also augment ADHD treatment effects by a common catecholaminergic mechanism. METHODS: Forty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ADHD participated in a randomized, double-blind, placebo-controlled, 12-week trial of 15 mg of L-methylfolate in combination with osmotic-release oral system methylphenidate. Osmotic-release oral system methylphenidate was dose optimized over the first 6 weeks. We evaluated the effects on ADHD symptoms, self-report on the Behavior Rating Inventory of Executive Function of executive function, methylphenidate dosing, neuropsychological test measures, the Adult ADHD Self-report scale, emotional dysregulation, social adjustment, and work productivity, as well as moderating effects of body mass index, autoantibodies to folate receptors, and select genetic polymorphisms. RESULTS: L-Methylfolate was well tolerated, with no significant effect over placebo except improvement from abnormal measures on the mean adaptive dimension of the ASR scale (χ = 4.36, P = 0.04). Methylphenidate dosing was significantly higher in individuals on L-methylfolate over time (χ = 7.35, P = 0.007). Exploratory analyses suggested that variation in a guanosine triphosphate cyclohydrolase gene predicted association with higher doses of methylphenidate (P < 0.001). CONCLUSIONS: L-Methylfolate was associated with no change in efficacy on measures relevant to neuropsychiatric function in adults with ADHD, other than suggestion of reduced efficacy of methylphenidate. Further investigation would be required to confirm this effect and its mechanism and the genotype prediction of effects on dosing.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Metilfenidato/uso terapéutico , Tetrahidrofolatos/uso terapéutico , Administración Oral , Adulto , Trastorno por Déficit de Atención con Hiperactividad/genética , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Preparaciones de Acción Retardada/uso terapéutico , Dietoterapia , Suplementos Dietéticos , Inhibidores de Captación de Dopamina/administración & dosificación , Inhibidores de Captación de Dopamina/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Función Ejecutiva/efectos de los fármacos , Femenino , Receptor 1 de Folato/inmunología , GTP Ciclohidrolasa/genética , Humanos , Masculino , Metilfenidato/administración & dosificación , Pruebas Neuropsicológicas , Proyectos Piloto , Tetrahidrofolatos/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is defined as a disorder of impaired attention and/or behavioral control. Studies suggest that the condition can dispose individuals to a higher risk of automobile accidents. ADHD symptoms respond to pharmacotherapy in a majority of uncomplicated cases. Evidence on how pharmacotherapies for ADHD impact driving behavior or outcomes could allow clinicians to support on-road safety rationally. We therefore undertook a review to identify the evidence base to date indicating positive or negative effects of pharmacotherapies on driving behavior in individuals with ADHD. Further, we evaluated the level of evidence for these effects, their specificity to ADHD, and how they may inform clinical care. We identified studies involving pharmacotherapy for ADHD that evaluated driving-related activities or outcomes. We then categorized these studies by the mode of measurement used and by the ADHD specificity of the driving behaviors measured. Finally, we extracted themes of interest to clinical practice in pharmacologic intervention. In total, 14 studies, involving 2-61 subjects diagnosed with ADHD, looked at computer-measured, observer-measured, or self-reported driving behavior correlates of pharmacotherapy during simulation or on-road driving. Of these studies, 13 involved psychostimulant agents and two used atomoxetine. All but three investigations (one of methylphenidate, one of mixed amphetamine salts, and one of atomoxetine) found favorable changes in measures such as steering and braking behaviors or reaction to unexpected events. One study found adverse effects on driving at hour 17 following mixed amphetamine salt administration. Four studies compared two pharmacotherapies, and each found differences in measured driving behavior between the therapies. One study explored impact on ADHD-specific driving impairments, and the same study was the only one to explore correlation of clinical measures (ADHD symptoms and self-reported driving behavior) with medication-associated changes-finding dissociation between changes in ADHD symptoms and changes in measured driving measures. While data to date are limited on the ADHD-specific effects of pharmacotherapies used for ADHD on driving, it is clear from our review that these agents have effects on driving-relevant behaviors. Further research is urgently needed to develop an evidence base for clinically predictable effects of pharmacotherapy on driving safety in individuals with ADHD. If possible, clinicians should evaluate the positive and negative effects of pharmacotherapy on driving in their clients.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Conducción de Automóvil , Estimulantes del Sistema Nervioso Central/uso terapéutico , Desempeño Psicomotor/efectos de los fármacos , Percepción Visual/efectos de los fármacos , Práctica Clínica Basada en la Evidencia/estadística & datos numéricos , HumanosRESUMEN
Although previously considered a disorder of childhood, studies in the last decade have demonstrated that attention-deficit hyperactivity disorder (ADHD) continues to impair function into adulthood and responds to pharmacotherapy. Due to age-specific changes in roles and challenges, it is possible that presentation and response to intervention may differ between older and younger adults. A literature search for papers that identified older adults with ADHD, including papers describing its epidemiology, manifestation, and treatment, was the basis for this paper. There is a paucity of data on ADHD in older adults; however, small observational studies have characterized the presence, impact, and treatment of ADHD in adults over the age of 50 years, and larger epidemiologic studies have demonstrated that ADHD symptoms exist in older adulthood. Optimal criteria for diagnosis of ADHD and methods of treating ADHD in older individuals have not been systematically explored. In light of the limited data, this review discusses considerations for differential diagnosis and safe pharmacotherapy of ADHD in older adults.