Weisler R, Young J, Mattingly G, Gao J, Squires L, Adler L. Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. CNS Spectr 14: 573-585

Department of Psychiatry, University of North Carolina, Chapel Hill, USA.
CNS spectrums (Impact Factor: 2.71). 10/2009; 14(10):573-85.
Source: PubMed


To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).
Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.
A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P < .0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P < .0001).
LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.

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    • "However, most RCTs of adult ADHD are short-term studies of 4–10 weeks duration (Faraone and Glatt, 2010; Fredriksen et al., 2013). Only a few last 24 weeks or longer (Rosler et al., 2009; Biederman et al., 2010; Adler et al., 2009a, 2009b; Young et al., 2011), and some short-term trials have been conducted with open-label extensions (Ginsberg and Lindefors, 2012; Buitelaar et al., 2011; Marchant et al., 2010; Wender et al., 2011; Adler et al., 2009b; Weisler et al., 2009). Although these studies show beneficial effects of medication , their clinical relevance is unresolved, since the samples are typically small at endpoints due to the high rates of dropout , and selection bias is also likely since patients have typically had low rates of comorbid disorders (Weiss et al., 2006). "
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    ABSTRACT: Abstract How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to ‘real-world’ clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed.
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    • "The overall frequency of TEAEs for LDX-treated patients did not differ greatly between studies with durations of 4 weeks or 7–10 weeks (Table 1). This may have been because most TEAEs are reported to occur within 4 weeks of treatment initiation [18, 19, 23, 24, 29, 30]. It is also possible that the dose-optimized design of studies 317, 325, and 403 may have reduced the rate of TEAEs compared with the forced-dose titration design of the three shorter trials. "
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    ABSTRACT: Here 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). A 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]). In 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. The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.
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    • "Lisdexamfetamine, which can be administered once-daily, is a prodrug that is metabolised by red blood cells to yield its active metabolite, d-amphetamine, and L-lysine (Pennick, 2010). Lisdexamfetamine has been shown to be effective in the treatment of ADHD (evidence level Ia) in a number of randomised, double-blind, placebo-controlled trials that have been performed in children (Biederman et al., 2007a, 2007b) and adults (Adler et al., 2008), and also in open-label, long-term investigations (Findling et al., 2008; Weisler et al., 2009). The side-effect profile of this prodrug (Vyvanse® US Prescription Drug Label, 2012) is similar to that of d-ampheta-mine or methylphenidate (Heal et al., 2013), but there is evidence from studies performed in drug-experienced human volunteers that indicates its liability for recreational abuse may be substantially lower than that of immediate-release d-amphetamine (Jasinski and Krishnan, 2009a, 2009b). "
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.
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