This cohort study of a Finnish national multiyear birth cohort uses instrumental variable analysis to investigate whether methylphenidate alters the long-term risk of psychotic disorder in children with attention-deficit/hyperactivity disorder.
Methylphenidate and the risk of psychosis in adolescents and young adults: a population-based cohort study
Background There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder. Methods In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12–30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis. Findings We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80–1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69–1·30) among those with a history of psychosis. Interpretation Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis. Funding Swedish Research Council, National Institute of Mental Health, UK National Institute of Health Research Nottingham Biomedical Research Centre.
Methylphenidate and Short-Term Cardiovascular Risk
This cohort study examines the risks of cardiovascular disease after 6 months of methylphenidate treatment in individuals with attention-deficit/hyperactivity disorder.
Intravenous Methylphenidate Abuse
Data are presented from a case series of 22 patients who abused methylphenidate hydrochloride (Ritalin-SR). The abuse pattern and symptoms of toxicity were similar to that seen with cocaine hydrochloride and amphetamine sulfate addiction; yet, the morbidity and mortality seen in this case series...
Occurrence of Psychosis and Bipolar Disorder in Individuals With ADHD Treated With Stimulants
This systematic review and meta-analysis evaluates the association between psychosis or bipolar disorder and stimulant treatment among individuals with attention-deficit/hyperactivity disorder.
How easy is it to get addicted to methylphenidate?
Hi so I (18m) will start taking prescripted methylphenidate (medikinet) next thursday and i’ve never taken any stimulants (besides caffeine and…
Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets
BACKGROUND:Non-medical use of methylphenidate is increasing. Little is known about potential acute medical complications associated with recreational use of methylphenidate. STUDY AIM: To identify medical problems associated with methylphenidate abuse. METHODS: Retrospective case series of methylphenidate abuse cases presenting to an inner city emergency department. RESULTS: We identified 14 cases of methylphenidate abuse between 2003 and 2010. Ten of these patients abused methylphenidate alone while four co-ingested other drugs, mainly alcohol. The route of ingestion was oral in nine patients, nasal in one and intravascular in four. Severe toxicity was exclusively observed in users who injected the drug. Two cases involved accidental intra-arterial injection and resulted in tissue necrosis leading to the amputation of a forearm and of fingertips, respectively. Clinical findings in the non-serious cases included mild to moderate symptoms and signs of sympathetic nervous stimulation such as agitation, tachycardia, hypertension, anxiety, hallucination, headache, tremor and dizziness. Nine of the fourteen patients were taking methylphenidate as a prescribed drug. Eight patients were former or current multiple substance abusers. CONCLUSION: Methylphenidate misuse is not a significant burden for emergency departments in Switzerland. Oral and nasal administration of methylphenidate did not result in severe toxicity. However, injection of crushed methylphenidate pills lead to serious local toxicity. Most patients with methylphenidate abuse had a prescription for the drug indicating deviation from medical use. A history of multiple substance use may be a risk factor for non-medical use of methylphenidate.
4-Fluoromethylphenidate
4-Fluoromethylphenidate is a stimulant drug that acts as a higher potency dopamine reuptake inhibitor than the closely related methylphenidate.
Timescales of developmental toxicity impacting on research and needs for intervention
Abstract Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision‐making must be weighed against the costs and necessary duration of research, as well as the long‐term costs to human health because of delayed protection of vulnerable early‐life stages of human development and, possibly, future generations. Although two‐generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY ‐ BPA ‐type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity ( PPTOX ) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm.
Chronic methylphenidate abuse: Effects on behaviour, redox homeostasis, and cholinergic system
Methylphenidate (MPH) (metil 2-fenil-2-(piperidin-2-il) acetato) is used as a drug of abuse as well as a cognitive enhancer owing to its amphetaminic structure. The objective of this study was to evaluate whether chronic exposure to an abusive context and dose of MPH (80 mg/L for 15 min/day for 7 days) in adult life causes behavioural changes related to anxiety, fear, sociability, locomotion, and memory as well as altered levels of biochemical markers, cortisol, and the cholinergic system. Here we used the zebrafish (Danio rerio) as a translatio Nnal model. We showed that fish exposed to MPH showed marked hypolocomotion and anxiogenic patterns, fear behaviour, and memory delay. MPH exposure also increased the levels of antioxidant enzymes, non-protein thiols, and reactive oxygen species compared with those in the control group, and the redox status was altered at the cerebral and peripheral levels. The cholinergic system exhibits a reduction in signalling and an increase in cortisol levels. Our results clarified the mechanisms involved in the toxicity elicited by the abusive use of MPH. Overall, our results demonstrated that chronic administration of an abusive dose of MPH in individuals without a diagnosis of attention deficit hyperactivity disorder (ADHD) can cause important damage.
How and when to take methylphenidate for adults
NHS medicines information on dosage for methylphenidate for adults, how to take it and what to do if you miss a dose or take too much.
Dose dependence of prenatal fluoride exposure associations with cognitive performance at school age in three prospective studies
Abstract Background Fluoride may be a developmental neurotoxicant at elevated exposures. We merged new data from a prospective Odense Child Cohort (OCC) with results from two previous birth cohort studies from Mexico and Canada to characterize the dose–effect relationship in greater detail. Methods The OCC contributed 837 mother–child pairs to the total of >1500. We measured creatinine-adjusted urine-fluoride concentrations in maternal urine samples obtained during late pregnancy. Child IQ was determined at age 7 years using an abbreviated version of the Wechsler Intelligence Scales for Children. Findings from the three cohorts were used to calculate the joint benchmark concentration (BMC) and the lower confidence limit (BMCL) after adjustment for covariables. Results In the OCC, urine-fluoride concentrations varied between 0.08 and 3.04 mg/l (median 0.52 mg/l) but were not significantly associated with full-scale IQ at age 7 years (β = 0.08; 95% confidence interval −1.14 to 1.30 for a doubling in exposure). No difference was apparent between boys and girls. In the OCC, the BMC was 0.92 mg/l, with a BMCL of 0.30 mg/l. The joint analysis of all three cohorts showed a statistically significant association between urine-fluoride and IQ, with a BMC of 0.45 mg/l (BMCL, 0.28 mg/l), slightly higher than the BMC previously reported for the two North American cohorts alone. Conclusions As the BMCL reflects an approximate threshold for developmental neurotoxicity, the results suggest that pregnant women and children may need protection against fluoride toxicity.
The association between attention-deficit/hyperactivity (ADHD) symptoms and self-employment
Attention-deficit/hyperactivity (ADHD) symptoms have been associated with the decision to become self-employed. Although these symptoms are generally regarded as disadvantageous, there may also be a bright side. To our knowledge, however, there has been no systematic, epidemiological evidence to support this claim. This paper examines the association between ADHD symptoms and self-employment in a population-based sample from the STAGE cohort of the Swedish Twin Registry (N = 7208). For replication, we used a sample of Dutch students who participated in the Global University Entrepreneurial Spirit Students' Survey (N = 13,112). In the Swedish sample, we found a positive association with self-employment for both general ADHD symptoms [odds ratio (OR) 1.13; 95 % confidence intervals (CI) 1.04-1.23] and hyperactivity symptoms [OR 1.19; 95 % CI 1.08-1.32], whereas no association was found for attention-deficit symptoms [OR 0.99; 95 % CI 0.89-1.10]. The positive association between hyperactivity and self-employment was replicated in the Dutch student sample [OR 1.09; 95 % CI 1.03-1.15]. Our results show that certain aspects of ADHD, in particular hyperactivity, can have a bright side, as they are positively associated with self-employment.
Safety of Safety Evaluation of Pesticides: developmental neurotoxicity of chlorpyrifos and chlorpyrifos-methyl
Authorization of pesticides for market release requires toxicity testing on animals, typically performed by test laboratories on contract with the pesticide producer. The latter provides the results and summary to the regulatory authorities. For the commonly used pesticide chlorpyrifos, an industry-funded toxicity study concludes that no selective effects on neurodevelopment occur even at high exposures. In contrast, the evidence from independent studies points to adverse effects of current exposures on cognitive development in children. We reviewed the industry-funded developmental neurotoxicity test data on chlorpyrifos and the related substance chlorpyrifos-methyl. We noted treatment-related changes in a brain dimension measure for chlorpyrifos at all dose levels tested, although not been reported in the original test summary. We further found issues which inappropriately decrease the ability of the studies to reveal true effects, including a dosage regimen that resulted in too low exposure of the nursing pups for chlorpyrifos and possibly for chlorpyrifos-methyl, and a failure to detect any neurobehavioral effects of lead nitrate used as positive control in the chlorpyrifos study. Our observations thus suggest that conclusions in test reports submitted by the producer may be misleading. This discrepancy affects the ability of regulatory authorities to perform a valid and safe evaluation of these pesticides. The difference between raw data and conclusions in the test reports indicates a potential existence of bias that would require regulatory attention and possible resolution.
151 Million People Affected: New Study Reveals That Leaded Gas Permanently Damaged American Mental Health
Childhood lead exposure from leaded gasoline has caused widespread mental health issues, particularly in Generation X, highlighting the dangers of delayed environmental regulation.
High intelligence: A risk factor for psychological and physiological overexcitabilities
High intelligence is touted as being predictive of positive outcomes including educational success and income level. However, little is known about the difficulties experienced among this population. Specifically, those with a high intellectual capacity (hyper brain) possess overexcitabilities in various domains that may predispose them to certain psychological disorders as well as physiological conditions involving elevated sensory, and altered immune and inflammatory responses (hyper body). The present study surveyed members of American Mensa, Ltd. (n=3715) in order to explore psychoneuroimmunological (PNI) processes among those at or above the 98th percentile of intelligence. Participants were asked to self-report prevalence of both diagnosed and/or suspected mood and anxiety disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and physiological diseases that include environmental and food allergies, asthma, and autoimmune disease. High statistical significance and a remarkably high relative risk ratio of diagnoses for all examined conditions were confirmed among the Mensa group 2015 data when compared to the national average statistics. This implicates high IQ as being a potential risk factor for affective disorders, ADHD, ASD, and for increased incidence of disease related to immune dysregulation. Preliminary findings strongly support a hyper brain/hyper body association which may have substantial individual and societal implications and warrants further investigation to best identify and serve this at-risk population.
Taming the endless scroll? Short-form videos, digital routines and neurocognitive outcomes in youth
Short-form videos (SFVs) deliver digital content in a way that sets them apart from other media. Concerns have arisen that such user interfaces may diminish attention, memory and emotional wellbeing in young people, yet evidence has not previously been synthesised for this demographic and in isolation from other media types. To assess the association between exposure to SFV-interfaces and neurocognitive outcomes in individuals aged $$\varvec{\le 25}$$years, and to appraise the certainty of this evidence. Following PRISMA and Cochrane guidelines, four databases (PubMed, PsycINFO, WoS, Cochrane Reviews) were searched (2015–2025). Of 1,498 records, 42 studies (N = 46,912; mean age = 16.8) met the PICOS criteria. Most were cross-sectional (88%), with two longitudinal, one EEG, and one MRI study. Risk of bias and quality were evaluated using GRADE. Heavy, unstructured SFV use (typically $$\varvec{\ge 4}$$h/day) was consistently associated with: small-to-moderate increases in inattention ($$\varvec{\beta \approx 0.30}$$) and impulsivity ($$\varvec{\beta \approx 0.25}$$); moderate reductions in working-memory span ($$\varvec{\beta \approx -0.75}$$) and self-regulation ($$\varvec{\beta \approx -0.45}$$); moderate elevations in anxiety ($$\varvec{\beta \approx 0.35}$$), depression ($$\varvec{\beta \approx 0.48}$$) and stress ($$\varvec{\beta \approx 0.32}$$); and a moderate-to-large surge in addiction symptoms ($$\varvec{\beta \approx 0.60}$$). Two cross-sectional imaging studies also reported associations between heavier short-video use and neurobiological measures. These included grey-matter volume differences in the orbitofrontal cortex and cerebellum, altered resting-state signal synchrony, and reduced P300 amplitudes. Protective factors included supportive environments, digital routines, and digital literacy. Consistent, albeit preliminary, evidence links excessive SFV watching to cognitive and emotional challenges in youth. Longitudinal and experimental studies are urgently needed, alongside trials of modifiable levers to reduce addiction-like use and related harms.
