Methylphenidate use in geriatric depression: A systematic review.

Risques du méthylphénidate au long cours

BackgroundConcerns have been raised over the safety of methylphenidate (MPH), with regard to adverse effects on growth and blood pressure. Our study investigates whether, and to what extent, methylphenidate use in boys with ADHD is associated with having low body mass index (BMI), having low height, and increased systolic and diastolic blood pressure.MethodsData used for this study stem from the German KiGGS dataset. Three different groups of boys aged 6–15 years were included in the analysis: ADHD patients who used MPH for less than 12 months; ADHD patients who used MPH for 12 months or more; and ADHD patients without current MPH treatment. Each of these three groups was compared to a non-ADHD control group regarding low weight (BMI ≤ 3rd percentile), low height (≤3rd percentile) and raised systolic and diastolic blood pressure. For growth outcomes, boys were categorized according to age (< 11 years/≥11 years, to account for pubertal maturation). Multivariable logistic regression was conducted to test for associations.Results4244 boys were included in the study; MPH < 12 months: n = 65 (n = 36 < 11 years), MPH ≥ 12 months: n = 53 (n = 22 < 11 years), ADHD controls: n = 320 (n = 132 < 11 years), non-ADHD controls: n = 3806 (n = 2003 < 11 years). Pre-pubertal boys with MPH use less than 12 months and pubertal/postpubertal boys with MPH use of 12 months or greater were significantly more likely to have a BMI ≤ 3rd percentile compared to non-ADHD controls. Boys from the ADHD control group were significantly less likely to have a raised systolic blood pressure compared to non-ADHD controls. Beyond that, no significant between group differences were observed for any other growth and BP parameter.ConclusionThe analyses of the KiGGS dataset showed that MPH use in boys with ADHD is associated with low BMI. However, this effect was only observed in certain groups. Furthermore, our analysis was unable to confirm that MPH use is also associated with low height (≤3rd percentile) and changes in blood pressure.

The behavioral effects of repeated methylphenidate (MPH) treatment were assessed in young rats. In 4 experiments, rats (starting at Postnatal Day 10 or 16) were pretreated on 5 consecutive days with saline or MPH (2.5-20.0 mg/kg i.p.). Sensitization was assessed after 1 or 7 abstinence days, with rats receiving a test day challenge injection of either a low dose of MPH (2.5 mg/kg) or the same dose of MPH as given during pretreatment. Results show that a test day injection of 2.5 mg/kg MPH produced a sensitized locomotor response in rats pretreated with 2.5-20.0 mg/kg MPH. This MPH-induced locomotor sensitization was evident only after 1 abstinence day. Various pretreatment doses of MPH (5, 10, 15, or 20 mg/kg) were capable of sensitizing the stereotyped sniffing of young rats, but only rats pretreated and tested with the highest dose (20 mg/kg) of MPH showed an augmented stereotyped sniffing response that was still robust after 7 abstinence days. Results indicate that young rats are capable of exhibiting sensitization after an extended abstinence period, which contrasts with previous research suggesting that psychostimulant treatment does not produce long-term sensitization in young rats.

To examine the effects of stimulant medication on the sleep functioning of children with attention-deficit/hyperactivity disorder (ADHD) and identify predictors of sleep problems as a side effect of taking stimulant medication. One hundred sixty-three stimulant-naïve children (72% boys) aged 7 to 11 years diagnosed with ADHD (120 with ADHD predominantly inattentive type, 43 with ADHD combined type) participated in a 4-week, randomized, double-blind, placebo-controlled trial of once-daily (long-acting) methylphenidate (MPH). Parents completed weekly side-effect ratings including an item related to sleep problems. Ten percent of patients had parent-rated sleep problems before the initiation of medication. Rates of parent-rated sleep problems during MPH titration generally increased with increasing MPH dose (placebo: 8%; low dose: 18%; medium dose: 15%; high dose: 25%). Differences emerged between children with (n = 16) or without (n = 147) preexisting sleep problems. Although 23% of children without preexisting sleep problems went on to have sleep problems at the highest MPH dose, only 37.5% of children with preexisting sleep problems still had sleep problems at the highest MPH dose. Lower weight and lower body mass index (BMI) were associated with increased sleep problems during MPH titration. This study demonstrated a general association between increased MPH dose and increased sleep problems in children with ADHD, particularly for children of lower weight/BMI. However, a substantial proportion of children with preexisting sleep difficulties no longer had sleep problems on the highest MPH dose, which may help explain mixed findings reported to date in studies examining the impact of MPH on sleep functioning in children with ADHD and suggests that MPH dose titration should not be avoided solely on the basis of a child's premorbid sleep problems. Future research is needed to replicate and extend these findings to more specific domains of sleep functioning and to identify differences between children with persistent or improved sleep functioning as a result of MPH use.

To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. Inpatient pediatric rehabilitation. In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. Multicenter, retrospective medical record review. Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.

Cocaine responsiveness or anhedonia in rats treated with methylphenidate during adolescence

Objective: The aim of this study was to compare the effect of methylphenidate (MPH) versus MPH + parent training in children with ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) over a 12-month period. Method: After careful screening, 120 children diagnosed with ADHD + ODD/CD were included in the study. Treatment consisted of ongoing medication management for 12 months, with or without participation in a parent-training program beginning after the 1st month. Participants were not randomly assigned to treatment groups because of ethical, practical, and methodological reasons. Results: Data analyses revealed that mother–child relationship improvements and symptom severity did not benefit from parent training. Conclusion: The results of this study highlighted the positive role of MPH in ADHD. No significant effects were observed after the addition of parent training to MPH treatment. Clinicians should carefully follow patients’ improvements and titrate the MPH dosage during long-term treatment.

IntroductionLisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Post hoc subgroup analyses were performed from two studies in children with ADHD to compare the efficacy of LDX in participants who had received prior methylphenidate (MPH) treatment with that of the overall study populations.MethodsStudy 1 (7-week; open-label design) and study 2 (randomized, double-blind, placebo-controlled, crossover, laboratory school design) enrolled children aged 6–12 years with ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Both studies excluded children whose prestudy ADHD treatment provided effective control of ADHD symptoms with an acceptable safety profile. Post hoc efficacy analyses were performed in children who had received MPH within 6 months of study enrollment. Efficacy measures included the following scales: ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), Behavior Rating Inventory of Executive Function (BRIEF), Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), and Permanent Product Measure of Performance (PERMP).ResultsIn studies 1 and 2, 83/318 (26%) and 67/129 (52%) participants, respectively, had received MPH within 6 months and were not adequately controlled on current medication with acceptable tolerability; most of these participants had received long-acting MPH. In prior MPH participants, efficacy assessments demonstrated improvements from baseline (study 1) and versus placebo (study 2) that were comparable with those seen in the respective overall study population. Safety profiles were consistent with long-acting stimulant use.ConclusionIn two studies, children who had received prior MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study populations. For children with ADHD who were previously treated with MPH, LDX may, therefore, be an efficacious treatment option.

PP11.6 – 2858: ADHD predominantly inattentive subtype, interictal epileptiform discharges and use of methylphenidate for ADHD

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) frequently have comorbidities that are potential indications for antipsychotics (APs). Some studies have suggested that the combined use of methylphenidate (MPH) and APs is increasing in this population group. Longitudinal analyses and in-depth investigations on the substance level are lacking. This study aimed to estimate the cumulative proportion of concomitant AP/MPH use in children and adolescents with ADHD over a follow-up of up to 9 years and to describe patient characteristics stratified by specific AP drug. Based on claims data, concomitant AP/MPH use was identified among 67,595 children and adolescents with ADHD starting MPH treatment between 2005 and 2013. Characteristics and diagnoses-including those indicating appropriateness of AP use according to approved indications and/or guidelines-were examined at the time of first AP/MPH combination therapy. In addition, subsequent use of AP/MPH combination therapy was evaluated. The cumulative proportion of individuals with any AP/MPH combination therapy rose to over 6% within 9 years after initiating MPH. The most frequent APs first used in combination with MPH were risperidone (72%), pipamperone (15%), and tiapride (8%). Percentages of psychiatric hospitalization in the year preceding the first combination therapy with MPH were 33%, 43%, and 19%, respectively. The proportion of individuals with potentially appropriate use was high (>72%) in risperidone/MPH and tiapride/MPH and low (15%) in pipamperone/MPH combination users. Conduct disorders and tic disorders were frequent in users who were prescribed MPH with risperidone and tiapride, respectively. One-quarter of patients with AP/MPH combination therapy were one-time-only combination users. Our study suggests that a considerable proportion of children and adolescents with ADHD receive MPH in combination with APs and that this is a factor not only during the first years of MPH treatment. ADHD guidelines should specify algorithms concerning the use of AP medication.

ObjectiveChildren with attention deficit hyperactivity disorder (ADHD) have more visits to the emergency department (ED) due to injuries than those without ADHD. However, no study has investigated whether children with ADHD have more ED visits or hospitalizations due to infectious diseases (IDs) and whether methylphenidate (MPH) treatment may reduce the risk.MethodThe incidence of ID-related ED visits or hospitalizations was defined as the main outcome. The Cox regression and conditional Poisson regression models were calculated to estimate hazard ratios (HRs) in the population level and relative risks for the self-controlled case series design, respectively.ResultsChildren with ADHD had higher rates of emergency visits (HR = 1.25, 95% CI: 1.23~1.27) and hospitalizations (HR = 1.28, 95% CI: 1.26~1.31) due to IDs than those without ADHD. In the ADHD subgroup, those who received MPH treatment have a reduced risk of emergency visits (HR = 0.10, 95% CI: 0.09~0.10) and hospitalizations (HR = 0.73, 95% CI: 0.71~0.75), compared to those without treatment. The risk of ID-related emergency visits decreased to 0.21 (95% CI: 0.21~0.22); and hospitalizations decreased to 0.71 (95% CI: 0.69~0.73). Within self-controlled analysis, it is demonstrated that compared with non-MPH exposed period, children with ADHD had significantly decreased risks for infection-related emergency visits (RR = 0.73, 95% CI: 0.68~0.78) or hospitalizations (RR = 0.19, 95% CI: 0.17~0.21) during MPH-exposed periods.Conclusions and RelevanceThis is the first study that reported an increased risk of ID-related healthcare utilizations in children with ADHD compared to those without, and that such risks may be significantly reduced in ADHD children that received MPH treatment.

Methylphenidate effects in the young brain: friend or foe?

Methylphenidate alleviates manganese-induced impulsivity but not distractibility

Prospective follow-up studies found no chromosomal mutagenicity of methylphenidate therapy in ADHD affected children

Stimulants, such as methylphenidate (MPH), are beneficial for attention-deficit/hyperactivity disorder (ADHD), but individual response varies. A deeper understanding of the mechanisms underpinning response is needed. Previous studies suggest that a single MPH dose modulates resting-state functional connectivity (rs-fc). We investigated whether single-dose induced rs-fc changes were associated with post-dose optimization clinical response. Fifty-six adults with ADHD underwent rs-functional magnetic resonance imaging (rs-fMRI) under placebo and a single MPH dose, before starting MPH treatment. Clinical response was measured at two months. We tested if a single MPH dose (vs. placebo) shifted rs-fc; how these shifts were associated with treatment response (categorical approach); and whether these associations were driven by improvement on either ADHD symptom domain. A single MPH dose (vs. placebo) increased rs-fc in three subcortical-cortical and cerebellar-cortical clusters. Enhanced rs-fc between the cerebellar vermis (lobule 6) and the left precentral gyrus was associated with a greater probability of responding to treatment (χ2(7) = 22.740, p = .002) and with an improvement on both inattentive and hyperactive/impulsive symptoms (both p ≤ .001). We provide proof-of-concept that the brain functional response to a single MPH dose, administered before starting routine treatment, is indicative of two-month clinical response in adult ADHD. This may encourage future replication using clinically applicable measures.