Aggregated n-of-1 trials of central nervous system stimulants versus placebo for paediatric traumatic brain injury – a pilot study

Direk

Clin Psychopharmacol Neurosci

et al. 2016

Almost one-fifth of children who sustain a traumatic brain injury (TBI) are under the risk of attention problems after injury. The efficacy and tolerability of methylphenidate (MPH) in children with a history of TBI have not been completely identified. In this case report, MPH-induced manic symptoms in an adolescent with TBI will be summarized. A male patient aged 17 years was admitted with the complaints of attention difficulties on schoolwork and forgetfullness which became evident after TBI. Long-acting MPH was administered with the dose of 18 mg/day for attention problems. After one week, patient presented with the complaints of talking to himself, delusional thoughts, irritability and sleeplessness. This case highlights the fact that therapeutic dose of MPH may cause mania-like symptoms in children with TBI. Close monitarization and slow dose titration are crucial when considering MPH in children with TBI.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Manic Symptoms Due to Methylphenidate Use in an Adolescent with Traumatic Brain Injury

Direk

Clin Psychopharmacol Neurosci

et al. 2016

“…Thus far, there have been few studies examining the use of stimulant medication in treating TBI-related attention deficits in children [ 12 , 13 , 14 , 15 , 16 ]. One of the better controlled studies was a recent investigation by LeBlond and colleagues [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Traumatic Brain Injury-Related Attention Deficits in Children: A Controlled Treatment Trial with Lisdexamfetamine Dimesylate (Vyvanse)

et al. 2021

Attention deficits are among the most common and persistent impairments resulting from traumatic brain injury (TBI). This study was the first to examine the effects of lisdexamfetamine dimesylate (LDX, Vyvanse) in treating TBI-related attention deficits in children. It was an extension of a previous controlled trial with adults. This was a 12-week, randomized, double-blind, placebo-controlled, dose-titration, crossover trial. In addition to weekly safety monitoring, there were assessments on a broad range of neuropsychological and behavioral measures at baseline, 6-weeks, and 12-weeks. A total of 20 carefully selected children were enrolled, ranging from 10 to 16 years of age. The sample consisted of cases with mainly mild TBI (based on the known details regarding their injuries), but they had persisting attention deficits and other post-concussion symptoms lasting from 2 to 29 months by the time of enrollment. A total of 16 children completed the trial. One of the children withdrew due to a mild anxiety reaction while on LDX. There were no other adverse effects. Positive treatment results were found on both formal testing of sustained attention and in terms of parent ratings of attention, emotional status, behavioral controls, and various aspects of executive functioning. The findings also served to highlight broader insights into the nature of attention deficits and their treatment in children with TBI.

“…The condition should be chronic and require prolonged treatment; the therapies should have a rapid onset and offset of action; the response to treatment should be accurately measurable; and the physician should be willing to consider multiple therapies. Such trials have been performed in a variety of conditions, including chronic obstructive lung disease, osteoarthritis, neuropathic pain, palliative care, traumatic brain injury, and attention deficit-hyperactivity disorder [ 25 – 30 ]. The treatment of primary hypertension in children meets these criteria and is equally well suited for an n-of-1 trial.…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of antihypertensive treatment for older children with primary hypertension: study protocol for a series of n-of-1 randomized trials

Samuel

Samuels

Brooks

et al. 2016

Trials

BackgroundChildren are increasingly being diagnosed with primary hypertension. The absence of comparative effectiveness research of antihypertensive medications in children has contributed to considerable differences in prescribing practices among physicians treating children with primary hypertension. Even if parallel-group trials had established a best overall choice for most of these children, the best medication for an individual may differ from the best overall medication.Methods/designThis project consists of a series of systematically administered n-of-1 trials among older children to verify the need for ongoing antihypertensive treatment and, if so, to identify the preferred single drug therapy from among the three major classes of drugs commonly used for primary hypertension (angiotensin-converting enzyme inhibitors, calcium channel blockers, and diuretics). We will determine whether one of these is the preferred therapy for the great majority of patients. The “preferred” therapy is the drug which produces normal ambulatory blood pressure, with the greatest reduction in blood pressure without unacceptable side effects. We will recruit 50 patients from the Houston Pediatric and Adolescent Hypertension Program clinic. For each patient, the three drugs will be prescribed in random order and each drug will be taken for 2 weeks. The effectiveness of each therapy will be measured with 24-h ambulatory blood pressure monitoring, and tolerability will be assessed using a side effect questionnaire. Participants will rotate through treatment periods, repeating drugs and adjusting doses until the preferred therapy is identified. In assessing whether one of the medications is most effective for the majority of subjects, the primary outcome will be the percentage of participants for whom each drug is selected as the preferred therapy. We hypothesize that no drug will be selected for the great majority of the subjects, a finding that would support consideration of clinical use of n-of-1 trials. Secondary analyses will explore whether patient characteristics predict which medication will be selected as a preferred drug.DiscussionThis study will help optimize care of participating patients and provide evidence regarding the usefulness of n-of-1 trials in identifying appropriate treatment for children with hypertension and potentially other disorders.Trial registrationClinicaltrials.gov NCT02412761 (registered 4/8/2015).