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Characteristics and Theories Related to Acute and Chronic Tolerance Development
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Kramer et al.191 described the patterns and effects of chronic amphetamine intoxication. Tremendous degrees of tolerance to certain effects of the amphetamines can be developed in human subjects. Whereas the usual therapeutic dose of dextroamphetamine taken orally is in the range of 10 to 20 mg daily,141 oral doses as large as 250 to 1,000 mg daily are not unheard of where sufficient drug is available to dependent individuals.115,141 Even more remarkable accounts of tolerance have been given for the use of amphetamines intravenously.191,317 During the early phases of intravenous abuse, doses of 20 to 40 mg of dextroamphetamine or methamphetamine are injected three or four times daily. But with the development of tolerance, the dose and frequency of administration are increased to the point that 100 to 300 mg doses may be injected repeatedly throughout the day. Kramer et al.191 cited the example of an individual who injected over 1,000 mg of methamphetamine every two hours up to a total of almost 15,000 mg in a single day apparently without serious morbidity. It is to be emphasized that such remarkable degrees of tolerance do not extend to all of the effects of the amphetamines. With repeated use, most individuals eventually exhibit toxic psychoses10,l56,295 and a variety of toxic physical effects.79,l74,191
Clinical Psychopharmacology of Amphetamine and Related Compounds
Published in John Caldwell, S. Joseph Mulé, Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Narcolepsy was one of the first conditions to be treated successfully with amphetamine3 and remains one of the few (some would say the only) clinical indications for its use. While the required oral dose of dextroamphetamine (Dexedrine®) ranges from 5 to 120 mg/day, most patients respond to 10 mg two to four times daily. The most frequently reported side effects include irritability, insomnia, palpitations, muscle jerking, and sweating; dextramphetamine can also at times lead to a sustained increase in blood pressure.59 Some patients fail to respond at all, and about a third develop tolerance to the drug and require progressively larger doses. The closely related compound methylphenidate (Ritalin®), 20 mg two to four times daily, has been shown to be as effective as dextroamphetamine but with less likelihood of causing side effects.61 The same is true of levoamphetamine.62
Stimulant Use Disorder
Published in James MacKillop, George A. Kenna, Lorenzo Leggio, Lara A. Ray, Integrating Psychological and Pharmacological Treatments for Addictive Disorders, 2017
Allison M. Daurio, Mary R. Lee
Use of psychostimulants such as dextroamphetamine or methylphenidate as a replacement therapy for PUD has been studied analogous to other replacement therapies for opioid (methadone and buprenorphine) or nicotine dependence (nicotine replacement therapy). Initial nonrandomized studies of dextroamphetamine as a replacement therapy for PUD were promising. Treatment with dextroamphetamine reduced stimulant use and stimulant injections by half [68, 69]. Further, randomized trials yielded mixed results. During the treatment period, several studies reported no difference between placebo and dextroamphetamine [70, 73]; and others found up to a 40% reduction in psychostimulant use [74]. In contrast, during post-treatment follow-up, one of these studies reported that dextroamphetamine was associated with a reduced severity of dependence [72]. Methylphenidate, another psychostimulant, failed to show significant differences in cocaine abstinence or craving compared to placebo [75, 76].
Psychiatric and non-psychiatric drugs causing false-positive amphetamines urine test in psychiatric patients: a pharmacovigilance analysis using FAERS
Published in Expert Review of Clinical Pharmacology, 2023
Vera Battini, Giovanna Cirnigliaro, Luca Giacovelli, Maria Boscacci, Silvia Massara Manzo, Giulia Mosini, Greta Guarnieri, Michele Gringeri, Beatrice Benatti, Emilio Clementi, Bernardo Dell’Osso, Carla Carnovale
Agents commonly used to treat ADHD, including dextroamphetamine, lisdexamphetamine, and atomoxetine, were among the most frequently reported in the FAERS. Indeed, the second most frequent diagnosis was ADHD. Dextroamphetamine and lisdexamfetamine are psychostimulant agents derived from amphetamine and represent the first-line therapy for ADHD [79,80]. Atomoxetine inhibits the presynaptic norepinephrine transporter (NET), reducing the norepinephrine reuptake, and at the same time is a dopamine reuptake inhibitor in the prefrontal cortex. On the other hand, methylphenidate inhibits the dopamine reuptake by increasing prefrontal, striatal, and accumbal dopamine levels. Since adolescents and adults with ADHD are at high risk for SUD [81], the UDS is crucial in this specific clinical setting; it is therefore of paramount importance for clinicians to consider the possible cross-reactivity of these agents with other substances of abuse.
Open‐label pilot study of lisdexamfetamine for cocaine use disorder
Published in The American Journal of Drug and Alcohol Abuse, 2021
John J. Mariani, C. Jean Choi, Martina Pavlicova, Amy L. Mahony, Daniel J. Brooks, John Grabowski, Frances R. Levin
This 8-week outpatient pilot trial tested LDX in doses up to 140 mg under open-label conditions for the treatment of CUD. The objective of the study was to determine the ideal target dose range, tolerability, and feasibility of LDX as a pharmacotherapy for CUD. As most participants were able to tolerate the target dose of 140 mg for the duration of the study period, the tested dosing schedule, with a two-week titration, appears to be an appropriate dosing strategy. While most participants reported adverse effects, no participants discontinued study medication or exited the trial due to medication adverse effects. Out of the 16 participants with post-enrollment data, four (25%) participants required dose reductions. Of these four participants, three completed the entire trial, and one completed 75% of the study weeks, suggesting that a flexible-fixed dosing strategy for LDX can be effective in retaining participants who have adverse effects at a higher dose. In interpreting these results, it is important to consider the relative potency of LDX to dextroamphetamine. LDX is roughly 40–50% as potent as dextroamphetamine, which means that the dose of LDX tested in this study is roughly equivalent to 60 mg/day of dextroamphetamine. Participants in this study were using approximately 25% of days at baseline, which may limit the generalization of the tolerability the this LDX to more frequent users of cocaine.
Review of lisdexamfetamine dimesylate in children and adolescents with attention deficit/hyperactivity disorder
Published in Current Medical Research and Opinion, 2020
Jadwiga Najib, Ekaterina Didenko, Daria Meleshkina, Kamila Yusupov, Kateryna Maw, Justin Ramnarain, Maliha Tabassum
Limited published data exists regarding the safety of lisdexamfetamine and dextroamphetamine in intentional exposures by adults with even less data regarding the exploratory or unintentional exposures in pediatric patients. A retrospective observational case series of exposure cases of LDX, MAS XR, MAS immediate release (IR), as single agents reported to the to the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) between January 2007 and December 2012 noted the following clinical effects: agitation (20, 22, and 25%, respectively) and tachycardia (19, 23, and 24%), respectively. In children < 6 years of age, majority were exploratory (93%), while therapeutic errors were noted most in children aged 6–12 years (66%). In adolescents and adults, the most common reasons were suicide attempts, abuse and therapeutic errors (28, 20, and 19%, respectively). Majority of cases (62%) were managed in a health care facility with most treated in the emergency department without any negative sequela. The odds of abuse/misuse were higher for MAS IR than that for LDX or MAS XR and the odds of MAS XR abuse/misuse was higher than for LDX (2.3 (95% confidence interval [CI]: 2.0–2.4), and 1.9 (95% CI: 1.7–2.2), respectively64. Data is consistent from an earlier poison control review from five poison centers from eight states which noted tachycardia (73%) as the most common adverse event reported with LDX followed by agitation (53%), dystonia (47%), insomnia (20%), hallucinations (30%), fasciculations (20%), chest pain (13%), and vomiting (13%)65.