The Pharmacology and Clinical Outcomes of Amphetamines to Treat ADHD

Hodgkins, Paul; Shaw, Monica; McCarthy, Suzanne; Sallee, Floyd R.

doi:10.2165/11599630-000000000-00000

Cited by 39 publications

(29 citation statements)

References 94 publications

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“…Although the mechanisms of action of stimulants in the treatment of ADHD remain to be fully established, it is possible that differences in the pharmacologies of methylphenidate- and amfetamine-based stimulants contributed to the differential treatment responses observed for lisdexamfetamine and OROS-MPH [19]. Differences in formulation and the resulting pharmacokinetic profiles of these long-acting stimulants may also have influenced their therapeutic activity.…”

Section: Discussionmentioning

confidence: 99%

A Post Hoc Comparison of the Effects of Lisdexamfetamine Dimesylate and Osmotic-Release Oral System Methylphenidate on Symptoms of Attention-Deficit Hyperactivity Disorder in Children and Adolescents

et al. 2013

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IntroductionThere are limited head-to-head data comparing the efficacy of long-acting amfetamine- and methylphenidate-based psychostimulants as treatments for individuals with attention-deficit hyperactivity disorder (ADHD). This post hoc analysis provides the first parallel-group comparison of the effect of lisdexamfetamine dimesylate (lisdexamfetamine) and osmotic-release oral system methylphenidate (OROS-MPH) on symptoms of ADHD in children and adolescents.Study DesignThis was a post hoc analysis of a randomized, double-blind, parallel-group, dose-optimized, placebo-controlled, phase III study.SettingThe phase III study was carried out in 48 centres across ten European countries.PatientsThe phase III study enrolled children and adolescents (aged 6–17 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for a primary diagnosis of ADHD and who had a baseline ADHD Rating Scale IV (ADHD-RS-IV) total score of 28 or higher.InterventionEligible patients were randomized (1:1:1) to receive a once-daily, optimized dose of lisdexamfetamine (30, 50 or 70 mg/day), placebo or OROS-MPH (18, 36 or 54 mg/day) for 7 weeks.Main Outcome MeasuresIn this post hoc analysis, efficacy was assessed using the ADHD-RS-IV and Clinical Global Impressions-Improvement (CGI-I) scale. Responders were defined as those achieving at least a 30 % reduction from baseline in ADHD-RS-IV total score and a CGI-I score of 1 (very much improved) or 2 (much improved). The proportion of patients achieving an ADHD-RS-IV total score less than or equal to the mean for their age (based on normative data) was also determined. Endpoint was the last on-treatment visit with a valid assessment. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.ResultsOf the 336 patients randomized, 332 were included in the safety population, 317 were included in the full analysis set and 196 completed the study. The mean (standard deviation) ADHD-RS-IV total score at baseline was 40.7 (7.31) for lisdexamfetamine, 41.0 (7.14) for placebo and 40.5 (6.72) for OROS-MPH. The least-squares (LS) mean change (standard error) in ADHD-RS-IV total score from baseline to endpoint was −24.3 (1.16) for lisdexamfetamine, −5.7 (1.13) for placebo and −18.7 (1.14) for OROS-MPH. The difference between lisdexamfetamine and OROS-MPH in LS mean change (95 % confidence interval [CI]) in ADHD-RS-IV total score from baseline to endpoint was statistically significant in favour of lisdexamfetamine (−5.6 [−8.4 to −2.7]; p < 0.001). The difference between lisdexamfetamine and OROS-MPH in the percentage of patients (95 % CI) with a CGI-I score of 1 or 2 at endpoint was 17.4 (5.0–29.8; p < 0.05; number needed to treat [NNT] 6), and the difference in the percentage of patients (95 % CI) achieving at least a 30 % reduction in ADHD-RS-IV total score and a CGI-I score of 1 or 2 was 18.3 (5.4–31.3; p < 0.05; NNT 6). The difference between lisdexamfetamine and OROS-MPH in the percentage of patients (95 % CI) with an ADHD-RS-IV ...

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Section: Discussionmentioning

confidence: 99%

A Post Hoc Comparison of the Effects of Lisdexamfetamine Dimesylate and Osmotic-Release Oral System Methylphenidate on Symptoms of Attention-Deficit Hyperactivity Disorder in Children and Adolescents

et al. 2013

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“…Various long-acting AMP- and MPH-based stimulants have been developed, with the aim of relieving ADHD symptoms throughout the day using a once-daily dose [9]. Lisdexamfetamine dimesylate (LDX) is the first long-acting prodrug stimulant for the treatment of ADHD [10].…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of the Safety of Lisdexamfetamine Dimesylate

Coghill

Caballero²,

Sorooshian³

et al. 2014

CNS Drugs

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BackgroundHere we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD).MethodsA PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]).ResultsIn short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25–39 % of patients and insomnia by 11–19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX.ConclusionsThe safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.

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“…Currently, methamphetamine is one of the most widely used illicit drugs in China, and its use seems to be increasing [8]. Moreover, medicinal methamphetamines still remain in limited use for the treatment of narcolepsy, attention deficit hyperactivity disorder (ADHD), and obesity [4,9,10]. This escalating availability and use in humans together with the fact that there are probably more than 200 million dogs in China [11], may lead to the increasing likelihood of accidental or intentional methamphetamine exposure in dogs.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine intoxication in a dog: case report

Pei

Zhang²

2014

BMC Vet Res

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BackgroundMethamphetamine abuse has undergone a dramatic worldwide increase, and represents a significant and global issue for public health. Incidents of methamphetamine intoxication and death in humans are relatively commonplace. Because of its increasing illicit availability, together with legitimate use in human medicine, accidental or intentional exposure to methamphetamine in dogs is becoming a more likely scenario.Case presentationA 3-year-old, 3.7 kg intact female Miniature Poodle who had been intentionally fed an unknown amount of a crystalline-like substance developed extreme agitation, seizures, tachycardia, hyperthermia, hypertension, disseminated intravascular coagulation (DIC), bloody diarrhea, and dilated pupils. Blood work revealed leukocytosis, erythropenia, lymphocytosis, thrombocytopenia, coagulation abnormalities, but all to a mild extent, together with mild elevation in both alanine aminotranferease (ALT) and alkaline phosphatase (ALKP), and a mild decreased in glucose. Radiologic diagnosis revealed generalized, severe distension of the stomach and small intestinal tract with air. Immunochromatographic screening tests and gas chromatography mass spectrometry analysis confirmed methamphetamine intoxication and revealed concentrations of methamphetamine in blood and urine of 0.32 μg/mL and 2.35 μg/mL respectively. The dog demonstrated progressive improvement after supportive care, with the high fever resolved over the initial 24 hours of hospitalization, and agitation was successfully controlled beyond 48 hours after initial hospitalization. Hemostatic abnormalities were progressive improved after heparin therapy and supportive care. By the sixth day of hospitalization the dog was clinically well, and all laboratory data had returned to normal with the exception of a mild elevateion of ALKP.ConclusionTo the authors’ knowledge, this is the second case report of methamphetamine intoxication in dogs presented in veterinary practice in open literature so far. Although rare, methamphetamine intoxication should be considered as a differential diagnosis in dogs with a toxic substance ingestion history and with typical nervous and cardiovascular system symptoms. In such cases rapid diagnosis and aggressive intervention is important for prognosis. Blood methamphetamine concentration may be a helpful value for assessment of the severity of intoxication and prediction of clinical outcomes.

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The Pharmacology and Clinical Outcomes of Amphetamines to Treat ADHD

Cited by 39 publications

References 94 publications

A Post Hoc Comparison of the Effects of Lisdexamfetamine Dimesylate and Osmotic-Release Oral System Methylphenidate on Symptoms of Attention-Deficit Hyperactivity Disorder in Children and Adolescents

A Post Hoc Comparison of the Effects of Lisdexamfetamine Dimesylate and Osmotic-Release Oral System Methylphenidate on Symptoms of Attention-Deficit Hyperactivity Disorder in Children and Adolescents

A Systematic Review of the Safety of Lisdexamfetamine Dimesylate

Methamphetamine intoxication in a dog: case report

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