Dexamfetamine 3mg/5ml oral suspension

ImportanceThe use of stimulant medications has expanded substantially beyond the traditional treatment of attention-deficit/hyperactivity disorder (ADHD) to encompass a variety of other clinical conditions. Understanding the safety of these medications is important as their use increases across diverse patient populations.ObjectiveTo assess the safety of stimulant medications as reported in randomized clinical trials (RCTs) investigating methylphenidate, lisdexamfetamine, and other amphetamines.Data sourcesA comprehensive literature search was conducted from July 1, 2024, through February 28, 2025, using CINAHL, Embase, PubMed or MEDLINE, ScienceDirect, and Web of Science for studies published since 2000. Keywords included safety, adverse event, side effect, amphetamine, dextroamphetamine, stimulant, lisdexamfetamine, and methylphenidate.Study selectionRCTs published between January 1, 2000, and December 13, 2024, were included. These trials investigated the safety of stimulants in various clinical conditions, including ADHD, depression, binge eating disorder, schizophrenia, Alzheimer disease, and stimulant use disorders as well as in healthy individuals. Trials not focused on safety or adverse events (AEs) of stimulants, nonoriginal research, nonhuman research, trials with concomitant prescriptions other than stimulants, and trials without a placebo group were excluded.Data extraction and synthesisData extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Independent reviewers extracted study data, and a random-effects model was used to pool results. Heterogeneity was assessed using the I2 statistic.Main outcomes and measuresThe primary outcome was the risk ratio (RR) of developing any AE in participants taking stimulants vs placebo.ResultsA total of 93 RCTs were included after exclusions. The methodological quality assessment of the included trials showed overall low or unclear risk of bias. Trials with a duration of up to 52 weeks showed that stimulant medications were associated with an increased risk of overall AEs compared with placebo (RR, 1.34; 90% CI, 1.27-1.41), with high heterogeneity (I2 = 67%). Statistical significance of this finding was maintained when subgroups (ie, methylphenidate, lisdexamfetamine, and other amphetamines) were separately analyzed.Conclusions and relevanceThis meta-analysis found an increased risk of overall AEs associated with stimulants compared with placebo. Future research could provide more standardized and consistent assessments of this outcome and may improve understanding about misuse risk.

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BackgroundMany studies address the different treatments for crack cocaine use disorder without distinguishing between crack use and cocaine use disorder. Furthermore, they highlight various approaches, such as psychotherapeutic methods, medications, and social interventions, whose effectiveness remains contentious for crack use disorder. Our aim was to evaluate the relative effectiveness of these various treatments, specifically for crack use disorder.MethodsThis systematic review followed PRISMA guidelines; we searched PubMed, Embase, and Web of Science for studies between 2014 and July 2024.Eligibility criteriaDue to the limited number of available studies, we included all studies worldwide with full text available in English or French, published between 2014 and 2024, reflecting the recent increase in interest in crack use. Studies included adults aged 18 years or older with a clinical diagnosis of crack cocaine addiction based on a validated clinical scale. We excluded studies that did not distinguish between crack and cocaine use in their assessment of crack cocaine (or crack/cocaine) use disorder. We reported the randomized controlled trials (RCTs) results based on the type of interventions, including various outcomes: reduction of health (within the biopsychosocial model), increased accessibility and retention in healthcare, and reduction in drug use. The reliability of the evidence was assessed using Cochrane's tool for evaluating the risk of bias.ResultsWe identified 3,313 records, of which 46 were eligible, and 33 were finally included. Among the 33 studies, 15 were RCTs. Among the RCTs, the majority had a moderate risk of bias (8/15), followed by high risk (6/15), and only one had a low risk of overall bias. Contingency management was associated with higher abstinence, better treatment retention, and improvements in mental health, although the interpretability of these findings is limited by their generalizability. Pharmacological trials with dexamfetamine showed a reduction in drug use and an increase in abstinence, but only in a specific population receiving heroin-assisted treatment. Adjunct trials such as transcranial direct current stimulation yielded mixed findings, with some studies suggesting improvements in abstinence and quality of life, while others reported no significant effects. The findings highlight that tailored interventions supported by a contingency management approach may enhance engagement and treatment effectiveness.

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BackgroundAmong young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic.MethodsThree databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles.ResultsWe identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol.ConclusionsThe numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.

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The NICE Guideline on ADHD published in 2008 represents a major advance in evidence-based healthcare for children, young people and adults with ADHD. It draws together systematic reviews and expert opinion to produce clinical practice recommendations covering diagnosis, behavioural and pharmacological treatment and organisation of services for children and adults. This article summarises the key practice recommendations, highlights where gaps remain in the evidence base and describes some of the challenges for implementing the guideline in routine clinical practice. Some of the key recommendations of the NICE guideline are that ADHD should only be diagnosed by specialists in secondary care, that parent training/education should be used as first-line management in those with moderate ADHD but medication may be offered as first-line line treatment for severe ADHD, alongside other management strategies. The recommended medications are methylphenidate, atomoxetine and dexamfetamine. Attention is drawn to the fact that ADHD can occur in the presence of co-existing conditions such as learning disability and autism spectrum disorder.

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Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively) and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response), and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.

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The stimulants methylphenidate, dextroamfetamine, and lisdexamfetamine are prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) in adults.1-4 The prescribing of ADHD medications has increased notably since 2000,2 and, while they are considered to have good safety profiles, the number of poisonings in Australia has also increased.3, 4 Few reports on fatal poisonings with these drugs in adults have been published.5-8 We therefore conducted a retrospective observational study of deaths in Australia of people aged 15 years or older in which methylphenidate or (lis)dexamfetamine toxicity was implicated. We searched records in the National Coronial Information System (NCIS), a database of medico-legal death investigation records provided by the coroners’ courts of each Australian jurisdiction; all suspected drug overdose deaths in Australia must be reported to coroners for investigation. We included all closed cases (deaths in which the coronial process had been completed) of deaths during 1 January 2000 – 30 July 2024 in which methylphenidate was listed in the NCIS drug coding fields set as contributing to death. These fields code for external factors that contributed to death according to the coronial investigation. We also searched records for “ADHD”, “dexamphetamine”, “lisdexamphetamine”, and “dextroamphetamine”, as well as for their registered brand names. The Justice Human Research Ethics Committee (M0063) and the University of New South Wales Human Research Ethics Committee (HC220754) approved the study. Our report conforms with STROBE (Supporting Information) guidelines for observational study reports.9 We identified 64 deaths in which ADHD medications were implicated: 41 methylphenidate-related, 23 (lis)dexamfetamine-related. The mean age at death was 38.2 years (standard deviation, 10.7 years); 45 were men. Substance use problems were documented in 45 cases. Evidence from witnesses or the death scene indicated probable injection of the drug as the terminal event in 18 cases. ADHD diagnoses were documented for 37 people, other mental health problems for 44 people. Fifty-one deaths were deemed unintentional. In 49 cases, death was attributed to polysubstance toxicity; the most frequent clinical presentation form was sudden collapse (20 cases) (Box 1). Blood toxicology results that covered all major drug classes were available for 63 of 64 deaths. In no case was there evidence for use of both methylphenidate and (lis)dexamfetamine by an individual. In the cases in which they were detected, the median methylphenidate concentration was 0.06 mg/L (interquartile range [IQR], 0.03–0.20 mg/L; range, 0.01–2.50 mg/L); the median amfetamine concentration was 0.11 mg/L (IQR, 0.03–0.40 mg/L; range 0.01–1.20 mg/L). Other drugs were detected in 57 cases, most frequently sedative–hypnotics (35 cases: 33 benzodiazepines, two Z-class hypnotics) and antidepressants (32 cases) (Box 2). Autopsy reports were available for 47 cases. Cardiomegaly (heart weight exceeding the 95th percentile of normal weight range) was evident in twelve people (eight of 28 methylphenidate-related deaths, four of 19 (lis)dexamfetamine-related deaths) and severe coronary artery disease in 17 (eleven methylphenidate-related deaths, six (lis)dexamfetamine-related deaths). We identified 64 AHDH medication-related deaths in Australia during 2000–24. As methylphenidate was dispensed 1 270 397 times and (lis)dexamfetamine 2 001 934 times during 2023 alone,10 recorded ADHD medication toxicity-related deaths were rare. About 20% of the deaths were intentional, a proportion similar to those in other reports on stimulant poisoning in Australia,3, 4 and mental health or substance use problems were each recorded for about 70% of the people who died. Blood methylphenidate and amfetamine concentrations each ranged across two orders of magnitude. Reported blood concentrations in stimulant-related deaths in other studies ranged between 0.05 and 3 mg/L for methylphenidate and 0.5 to more than 40 mg/L for amfetamine.1, 5, 8 Drugs other than ADHD medications were detected in 49 cases; the concomitant use of other drugs can increase the toxicity risk of ADHD medications.3, 4, 11 The small number of deaths we identified provides reassurance that ADHD medications have a relatively good safety profile. There are, however, people for whom greater caution is warranted, including those with histories of substance misuse or of mental health problems. People who use these medications need to be warned about the risk of polypharmacy. Given that psychostimulants may exacerbate cardiovascular disease, and that evidence of such disease was frequently recorded at autopsy in the cases we reviewed, people with cardiovascular disease may require closer monitoring. Our series did not include deaths for which the coronial process was not yet complete. While all suspected fatal drug overdoses must be reported to coroners for investigation and will be recorded in the NCIS, some deaths may not have been reported. Clinical histories were restricted to details documented in NCIS case files. Blood drug concentrations at the time of death or hospital admission may not be the peak concentrations. Toxicological analysis may not have detected new psychoactive substances. Finally, assessment of intent is difficult in all studies of mortality; classification as self-harm was based upon the NCIS code for “intentional self-harm”. In summary, we identified 64 deaths of adults in which the ingestion of methylphenidate, dextroamfetamine, or lisdexamfetamine was deemed to be a contributory factor; in 20% of cases, the death was judged to be intentional. In 78% of cases, people had ingested more than one drug, and 70% of people had known substance use problems. This study was funded by the National Drug and Alcohol Research Centre at the University of New South Wales. The Centre is funded by the Australian Department of Health and Aged Care. We acknowledge the Victorian Department of Justice and Community Safety as the source organisation for the data we analysed and the National Coronial Information System as the data source. We thank the staff at the National Coronial Information System. Amy Peacock is funded by a National Health and Medical Research Council Investigator Fellowship (1174630). Open access publishing facilitated by the University of New South Wales, as part of the Wiley – University of New South Wales agreement via the Council of Australian University Librarians. Amy Peacock has received untied educational grants from Seqirus and Mundipharma for post-marketing surveillance of pharmaceutical opioids; the organisations had no role in study design, analysis, or reporting, and their funding was for work unrelated to this project. Michael Farrell has received untied educational grants from Seqirus, Mundipharma, and Indivior for post-marketing surveillance of pharmaceutical opioids; the organisations had no role in study design, analysis, or reporting, and their funding was for work unrelated to this project. The data upon which the study is based comprise confidential medico-legal documents. Ethics agreements and legal obligations prevent making these data available for sharing. STROBE statement Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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