Intake Of Methylphenidate Research Articles

EPA-0748 – Methylphenidate abuse: results of a french survey

Introduction Methylphenidate (MPH) abuse is well established especially among young people in USA. In France, MPH is indicated in treatment for attention deficit/hyperactivity disorder (ADHD) in children and narcolepsy in children and adults. Since its release onto the market, MPH abuse has been progressively increasing by individuals close to children treated with MPH and especially by patients to whom MPH is prescribed offlabel or obtained in black market. Objectives We report the results of a national survey on abuse and off-label use of methylphenidate. Methods Assessment of data collected between 2000 and 2011 from the Nots, OPPIDUM and OPEMA databases (tools for monitoring psychoactive substance misuse). Results MPH abuse and misuse were identified in 245 patients (168 in NotS, 68 in Oppidum and 9 in Opema). In NotS database, subjects were predominantly males (65%), aged between 12 and 74 years. When specified (122 cases), the sustained release form was used in 83% of cases and maximum daily MPH intake reached 2520 mg. MPH was injected (20%) or snorted (4%). Polydrug use was noted in 77% of cases. Regarding Oppidum and Opema databases, patients were exclusively adults and supported for drug addiction. In these cases, MPH was obtained by medical prescription (61%) and/or in black market (36%). Conclusion The medical practice of off-label prescription of MPH to treat ADHD or drug addiction in adults is the main problem in France. Another new aspect is that MPH is also diverted by teenagers, with or without ADH, for its stimulant and concentration-enhancing properties.

3240 mg long acting methylphenidate intake for suicide attempt

Pharmacotherapy is frequently used to treat symptoms of attention-deficit/hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. There are a few reported cases of overdose for suicide attempts or abuse with methylphenidate in current literature. Majority of these cases fully recovered after supportive therapy. We present a patient who ingested 3240 mg long acting methylphenidate for suicide attempt. He experienced increase in heart beat rate and blood pressure but he did not have additional symptoms. Although no serious neurological or cardiovascular event happened in this case, the supervised stimulant use is needed in child and adolescent population. Further studies are needed to evaluate the effect of methylphenidate overdose.

Attention‐deficit/hyperactivity disorder in childhood epilepsy: A neuropsychological and functional imaging study

Children with epilepsy have a significant risk for attention-deficit/hyperactivity disorder (ADHD), which is often accompanied by deficits in working memory performance. However, it is not yet clear whether there are specific differences in the underlying mechanisms of working memory capability between children with epilepsy-related ADHD and those with developmental ADHD. There is evidence that methylphenidate can improve the behavioral difficulties in children with developmental ADHD. Whether this medication has the same effect on ADHD symptoms in patients with epilepsy is not yet well understood. The aim of the present study is, therefore, to evaluate whether boys with epilepsy-related ADHD and developmental ADHD share a common behavioral, pharmacoresponsive, and neurofunctional pathophysiology. Seventeen boys with diagnosed combined epilepsy/ADHD, 15 boys with developmental ADHD, and 15 healthy controls (aged 8-14 years) performed on working memory tasks (N-back) while brain activation was recorded using functional magnetic resonance imaging. Each patient was tested twice: once after the intake of methylphenidate and once without in a counterbalanced order. On a behavioral level, we show that boys with epilepsy-related ADHD as well as those with developmental ADHD performed similarly poorly on tasks with high cognitive load when compared to healthy controls, and that intake of methylphenidate improved performance almost to normal levels in both ADHD groups. On the functional level, both patient groups showed similar reductions of activation in all relevant parts of the functional network of working memory when compared to controls. Of interest, intake of methylphenidate did not significantly alter this activity pattern. Our data show strong similarities between epilepsy-related and developmental ADHD on the behavioral, pharmacoresponsive, and neural level, favoring the view that ADHD with and without epilepsy shares a common underlying neurobehavioral pathophysiology.

Clinically-oriented monitoring of acute effects of methylphenidate on cerebral hemodynamics in ADHD children using fNIRS

ObjectiveAttention Deficit Hyperactivity Disorder (ADHD), a common developmental syndrome with inattention, hyperactivity, and impulsivity, is typically treated with the psychostimulant drug, methylphenidate (MPH). We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to search for a clinically implementable biological marker for the acute MPH effect on ADHD children. MethodsFollowing an MPH washout period, twelve ADHD children performed a go/no-go task before and 1.5h after MPH intake. fNIRS was used to monitor the lateral prefrontal cortical hemodynamics of ADHD children performing a go/no-go task. ResultsThere was no significant activation in the lateral prefrontal cortices examined before MPH intake. However, after MPH intake, significant MPH-elicited activation (oxygenated hemoglobin signal increase) was detected in the right lateral prefrontal cortex (LPFC) implicated with response inhibition functions. There was a large significant correlation between increases in task performance and activation in the right LPFC. ConclusionsThe improved cognitive performance was associated with activation in the right LPFC, which might serve as a biological marker to monitor the effect of MPH in ADHD children. SignificanceMPH-effect assessment in ADHD children using fNIRS can be performed within a 3h stay at a hospital during a single visit, and thus may be integrated into clinical practice.

Increased performance uncertainty in children with ADHD? - Elevated post-imperative negative variation (PINV) over the ventrolateral prefrontal cortex

BackgroundWe aimed to investigate the influences of attention deficit/hyperactivity disorder (ADHD) on response evaluation, as reflected by the postimperative negative variation (PINV), a slow event-related potential.MethodsWe investigated PINV as an indicator of performance uncertainty in an audio-visual contingent negative variation (CNV) paradigm with an interstimulus interval of 3 seconds. A constant, unilateral, quick motor reaction with either the right or the left thumb was required after an auditory forewarned (S1) visual imperative stimulus (S2). We examined 18 ADHD patients (combined or hyperactive-impulsive subtype) aged between 8 and 14 years and an age-, sex and IQ-matched control group of 19 healthy subjects using 64-channel high-density EEG. A first run was recorded drug-free, a second one under methylphenidate (MPH) medication in the ADHD group.ResultsWe found a significantly increased negativity of the PINV-component over the ventrolateral prefrontal cortex in ADHD children compared to the healthy control group. PINV amplitude was influenced by movement side, most likely due to the slightly more difficult task when left hand responses were required. After the intake of MPH, PINV amplitudes of ADHD children normalized.ConclusionsWe conclude that children with ADHD are likely to be more uncertain about the correctness of their performance and interpret the increased PINV as a hint towards compensatory mechanisms for a deficit in the evaluation of contingencies. Further studies are needed to assess the exact extent to which remainders of eye-movement related potentials contribute to PINV amplitude despite the correction for eye-artifacts.

Methylphenidate normalizes emotional processing in adult patients with attention-deficit/hyperactivity disorder: Preliminary findings

Emotional–motivational dysfunctions may significantly contribute to symptoms of attention-deficit/hyperactivity disorder (ADHD). Hyperactive–impulsive symptoms and sensation seeking could be the result of a search for reinforcers, and cognitive dysfunctions might be due to a low motivational drive. Emotional-motivational dysfunctions could also explain social dysfunctions in ADHD patients because they may lead to misinterpretations of emotional and social clues. Since methylphenidate (MPH) is the first choice as a pharmacological treatment in ADHD, we examined its influence on dysfunctional emotional processes. 13 adult ADHD patients were examined twice, without and after intake of MPH according to their personal medication regimen. The affect-modulated startle paradigm was used to assess physiological (affect-modulated startle response) and subjective (valence and arousal ratings) responses to pleasant, neutral and unpleasant visual stimuli. Healthy controls displayed affective startle modulation as expected, with startle attenuation and potentiation while watching pleasant and unpleasant pictures, respectively. In contrast, unmedicated ADHD patients displayed deficient responses to pleasant stimuli; no startle attenuation during the exposure to pleasant pictures was observed. However, MPH reinstated a normal affective startle modulation, as indicated by attenuation and potentiation associated with pleasant and unpleasant pictures, respectively. Valence and arousal ratings of patients were not affected by MPH. The data suggest that MPH as first choice treatment in ADHD has a positive impact on emotional processes in adult ADHD patients and points to the clinical relevance of emotional-dysfunctions in ADHD.

Non-motor dopamine withdrawal syndrome after surgery for Parkinson's disease: predictors and underlying mesolimbic denervation

Apathy has been reported to occur after subthalamic nucleus stimulation, a treatment of motor complications in advanced Parkinson's disease. We carried out a prospective study of the occurrence of apathy and associated symptoms, predictors and mechanisms in the year following subthalamic stimulation. Dopamine agonist drugs were discontinued immediately after surgery and levodopa was markedly reduced within 2 weeks. Apathy and depression were assessed monthly, using the Starkstein apathy scale and the Beck Depression Inventory. Dopamine agonists were re-introduced if patients developed apathy or depression. Preoperative non-motor fluctuations were evaluated using the Ardouin Scale. Depression, apathy and anxiety were evaluated both on and off levodopa. Analysis of predictors of apathy was performed using a Cox proportional hazard model. Twelve patients who developed apathy and a control group of 13 patients who did not underwent [11C]-raclopride positron emission tomography scanning before and after oral intake of methylphenidate. In 63 patients with Parkinson's disease treated with subthalamic stimulation, dopaminergic treatment was decreased by 82% after surgery. Apathy occurred after a mean of 4.7 (3.3-8.2) months in 34 patients and was reversible in half of these by the 12-month follow-up. Seventeen patients developed transient depression after 5.7 (4.7-9.3) months and these fell into the apathy group with one single exception. At baseline, fluctuations in depression, apathy and anxiety scores were greater in the group with apathy. Fluctuations in apathy, depression and anxiety ratings during a baseline levodopa challenge were also significant predictors of postoperative apathy in univariate analysis, but not motor and cognitive states or the level of reduction of dopaminergic medication. The multivariate model identified non-motor fluctuations in everyday life and anxiety score during the baseline levodopa challenge as two independent significant predictors of postoperative apathy. Without methylphenidate, [11C]-raclopride binding potential values were greater in apathetic patients bilaterally in the orbitofrontal, dorsolateral prefrontal, posterior cingulate and temporal cortices, left striatum and right amygdala, reflecting greater dopamine D2/D3 receptor density and/or reduced synaptic dopamine level in these areas. The variations of [11C]-raclopride binding potential values induced by methylphenidate were greater in non-apathetic patients in the left orbitofrontal cortex, dorsolateral prefrontal cortex, thalamus and internal globus pallidus and bilaterally in the anterior and posterior cingulate cortices, consistent with a more important capacity to release dopamine. Non-motor fluctuations are related to mesolimbic dopaminergic denervation. Apathy, depression and anxiety can occur after surgery as a delayed dopamine withdrawal syndrome. A varying extent of mesolimbic dopaminergic denervation and differences in dopaminergic treatment largely determine mood, anxiety and motivation in patients with Parkinson's disease, contributing to different non-motor phenotypes.

Effects of methylphenidate on working memory functioning in children with attention deficit/hyperactivity disorder

Background and aims Children with attention deficit/hyperactivity disorder (ADHD) often show deficits in working memory performance. Methylphenidate (MPH) is an effective medication to improve these cognitive difficulties. This study aimed to clarify which effect MPH induces on the underlying functional networks of working memory. Methods Fourteen boys diagnosed with ADHD and 12 healthy controls were investigated using functional magnetic resonance imaging (fMRI). Each patient was tested twice, once with medication and once without. The fMRI experiments consisted of three verbal N-back tasks with increasing difficulty. Functional images were acquired on a 3 Tesla head scanner. Results On the behavioral level, medicated patients performed similar to healthy controls and significantly better than without medication. On the functional level, patients showed the expected frontal and parietal activations, which were more pronounced in the 2- and 3-back tasks. Healthy controls showed significantly more activation in these regions and additional activation in the cerebellum. Interestingly, patients showed an additional effect of laterality. Left-sided frontal and parietal activation in patients was significantly less pronounced than in controls. Conclusion Functional data indicate different activation patterns in verbal working memory tasks between healthy controls and patients with ADHD irrespective of medication condition. Intake of MPH led to a clear improvement on a behavioral level. However, this effect was not reflected by changes in functional brain organization. MPH-induced changes leading to better performance in verbal working memory tasks might be very subtle and therefore not detectable by fMRI.

Arzneimittelinduzierte Psychose nach Einnahme von langsam freisetzendem Methylphenidat

The case report describes the sudden emerge of psychotic symptoms of a 13-year old boy, suffering from attention deficit hyperactivity disorder (ADHD), while he was treated with a modified--release formulation of methylphenidate. The question of the attending physician, whether the symptoms indicate an early beginning of schizophrenia or whether the symptoms can be considered as an overdose phenomenon of methylphenidate should be discussed. The knowledge of the pharmacokinetics of methylphenidate as modified--release formulation and the serum concentration values of methylphenidate and its metabolite provide information for interpretation of the case reported, with regard to the purpose of therapeutic drug monitoring (TDM) for methylphenidate. Finally we conclude that the ingestion of an unintended overdose of methylphenidate may have caused the boy's psychotic symptoms and that routine therapeutic serum concentrations of methylphenidate have to be correlated to the point of time when the blood was drawn in relation to the intake of methylphenidate.

Acute effects of methylphenidate on neuropsychological parameters in adults with ADHD: possible relevance for therapy

Recent research has demonstrated that attention-deficit/hyperactivity disorder (ADHD), one of the most common mental disorders in childhood, continues into adulthood. In adulthood, however, pharmacotherapy with psychostimulants still is an off-label treatment. Because of this we routinely administer a test dose of methylphenidate (MPH) prior to a continuous medication and measure MPH effects quantitatively and repeatedly employing a neuropsychological test battery. To probe if the acute effects of MPH are indeed helpful in predicting longer-term efficacy of MPH treatment we retrospectively analyzed the neuropsychological test results of 34 patients on continuous MPH medication. Two testing sessions had been performed without MPH (at baseline and 24 h after a single dose intake to control possible training effects), one after a single dose and one after 3-6 months of regular intake of MPH. A significant improvement of performance in tests assessing attentional, memory and executive functions after single medication was maintained on long term medication in those 23 patients available for follow-up. These results indicate that beneficial short term effects of MPH predict longer-term effects and may thus be helpful in the decision for an off-label treatment. Controlled prospective studies are now necessary.

Methylphenidate-Induced Changes in Cerebral Hemodynamics Measured by Functional Near-Infrared Spectroscopy

The aim of the present preliminary study was to evaluate the feasibility of measuring cerebral hemodynamic effects of a clinical dose of methylphenidate by near-infrared spectroscopy in 10 boys (median age, 10.7 years; range, 8.6-11.8 years) with developmental attention-deficit/hyperactivity disorder (ADHD). Using a Trail Making Test known to activate the left dorsolateral prefrontal cortex, cerebral hemodynamic changes show a lower increase of cerebral blood volume in the right prefrontal cortex (P = .033) and a lower increase of the tissue oxygenation index in the left prefrontal cortex (P = .015) in the condition after intake of methylphenidate compared with a drug-naive situation. A lower increase of the tissue oxygenation index indicates a changing regional oxygen metabolism and consumption induced by methylphenidate. Near-infrared spectroscopy is a sensitive tool for measuring pharmacological effects of methylphenidate on the cerebral hemodynamics.

Methylphenidate-Induced Orofacial and Extremity Dyskinesia

In this paper, we report the case of a 6(1/2)-year-old male patient diagnosed with attention-deficit/hyperactivity disorder (ADHD) who developed orofacial and extremity dyskinesias immediately after methylphenidate treatment. The episode lasted 5 hours, peaking in intensity 2 hours after the medication was administered before gradually subsiding. Five hours after the methylphenidate was administered, the child became extremely irritated and aggressive, which lasted approximately 2 hours. The patient's general intelligence (IQ) was measured to be below the normal range. The potential relationship between methylphenidate intake and the development of dyskinesia calls into question different mechanisms involving drug-receptor interaction or individual drug sensitivity related to a lower IQ. Our case report has practical implications for physicians by raising their awareness of dyskinesia as a potential side effect of methylphenidate treatment.

Self-Regulation of Visual Attention and Facial Expression of Emotions in ADHD Children

Objective: To test if visual focusing and mimic display as features of self-regulation in ADHD children show a curvilinear relation to rising methylphenidate (MPH) doses. To test if small dose steps of 2.5mg MPH cause significant changes in behavior. And to test the relation of these features to intellectual performance, parents' ratings, and clinical outcome. Method: Twenty-five children of a clinical convenience sample are filmed playing cards and doing oral arithmetic exercises without medication and after intake of MPH raised in steps of 2.5 mg. Recordings are revised by four blinded raters counting visual focus loss and rating the variability of patients' smile. Results: All hypotheses are confirmed. Best self-regulation coincides with best intellectual performance, highly significant improvement in parents' ratings, and good clinical outcome. Conclusion: The procedure could be helpful for MPH dose finding in the physician's practice and make therapy more efficient by means of a more precise dosage. (J. of Att. Dis. 2007; 10(4) 350-358)

Does Methylphenidate Reduce the Symptoms of Chronic Fatigue Syndrome?

Purpose Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life. Subjects and methods A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 × 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS). Results Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: −0.7, P = .010 for VAS; mean difference: −11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: −1.0, P = .001 for VAS; mean difference: −9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: −1.3, P <.0001) and compared with placebo (mean difference: −1.1, P <.0001). A clinical significant effect (≥33% improvement or CIS ≤76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients. Conclusions Methylphenidate at a dose of 2 × 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

Cerebral vasculitis following oral methylphenidate intake in an adult: A case report

Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.

A randomized, double-blind, placebo-controlled study of methylphenidate in patients with organic amnesia.

We examined the usefulness of methylphenidate (MPH) in the treatment of organic amnesia in a randomized, double-blind, placebo-controlled design. Twenty patients with amnesia due to closed head injuries (n = 10), viral encephalitis (n = 2), stroke lesions (n = 4), or surgical brain resections (n = 4) were assessed with a neuropsychological battery after the intake of MPH (10, 20, 30 or 40 mg), or placebo. We found no significant benefit of MPH for any of the cognitive tests.Copyright Lippincott-Raven Publishers