Lisdexamfetamine for Binge Eating Disorder in Adults
Lisdexamfetamine for Binge Eating Disorder in Adults
Objective To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED).
Data sources The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and 'binge', and by also querying the Web of Science (Thomson Reuters) and Embase (Elsevier) commercial databases, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.
Study selection All available clinical reports of studies were identified.
Data extraction Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
Data synthesis LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED. The recommended dose range is 50–70 mg/day. Approval for the treatment of BED was based on a clinical development programme that included an 11-week Phase II proof-of-concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70 mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50–70 mg/day. Statistically significant reductions in binge eating days/week, the primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT for response across all trials (as defined by a Clinical Global Impressions-Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo was 3 (95% CI 3–4), and NNT for remission (as defined by 4-week cessation of binge eating) for LDX vs. placebo was 4 (95% CI 4–6). Reductions in weight ranged between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX vs. placebo was 44 (95% CI 23–1971). The most commonly encountered AEs (incidence ≥ 10% and greater than the rate for placebo) were dry mouth, decreased appetite, insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3–5), 11 (95% CI 8–17), 11 (95% CI 8–18) and 19 (95% CI 11–75), respectively.
Conclusions LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week. Effect sizes were highly robust. Pending clinical trials include a long-term study examining maintenance of efficacy.
Lisdexamfetamine dimesylate (SPD489, LDX) is a central nervous system stimulant originally approved in 2007 for the treatment of attention deficit hyperactivity disorder (ADHD). On January 30, 2015, LDX received approval by the US Food and Drug Administration (FDA) for the treatment of moderate to severe binge eating disorder (BED).
BED is the most common eating disorder, with an estimated lifetime prevalence of 2.6% among US adults, more than the prevalence for bulimia and anorexia nervosa combined. Despite this, BED often goes unrecognised and untreated, in part because although binge eating was first described in 1959, it was not included as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders until the fifth edition (DSM-5), published in 2013. In the DSM-5 definition, BED is characterised by recurrent episodes of binge eating (eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstances and a sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. Binge episodes are also associated with eating rapidly, eating until feeling uncomfortably full, eating large amounts of food when not feeling physically hungry, eating alone because of feeling embarrassed by how much one is eating, and feeling disgusted with oneself, depressed or guilty afterwards. BED is distinguished from bulimia nervosa in that BED is not associated with regular compensatory behaviours such as purging or excessive exercise, or with dietary restriction, although frequent dieting may be reported. Since binge eating is often a secretive behaviour, and commonly associated with a high degree of embarrassment or shame, it is not ordinarily revealed unless the clinician makes a direct inquiry regarding eating patterns. In addition to physical comorbidities including obesity and metabolic syndrome (although many persons with BED are not obese), BED is commonly associated with other psychiatric disorders, including anxiety, depression, impulse control disorders and substance use. Approximately 4 of 5 adults with lifetime BED have at least one comorbid psychiatric disorder, and approximately 1 of 2 has three or more. BED is actively researched, with over 1600 publications listed in the US National Library of Medicine's PubMed resource containing the text words 'binge eating disorder', together with over 220 clinical trials registered in the US ClinicalTrials.gov registry. Psychological treatments including cognitive behavioural interventions have been recommended as first line and are supported by meta-analytic reviews. Unfortunately, routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED, and up to now there have not been any approved pharmacological interventions for this disorder.
The aim of this review is to synthesise the available data regarding the efficacy and safety of LDX for the treatment of BED and to place this new treatment option into clinical perspective.
Summary and Introduction
Summary
Objective To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED).
Data sources The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and 'binge', and by also querying the Web of Science (Thomson Reuters) and Embase (Elsevier) commercial databases, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.
Study selection All available clinical reports of studies were identified.
Data extraction Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
Data synthesis LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED. The recommended dose range is 50–70 mg/day. Approval for the treatment of BED was based on a clinical development programme that included an 11-week Phase II proof-of-concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70 mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50–70 mg/day. Statistically significant reductions in binge eating days/week, the primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT for response across all trials (as defined by a Clinical Global Impressions-Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo was 3 (95% CI 3–4), and NNT for remission (as defined by 4-week cessation of binge eating) for LDX vs. placebo was 4 (95% CI 4–6). Reductions in weight ranged between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX vs. placebo was 44 (95% CI 23–1971). The most commonly encountered AEs (incidence ≥ 10% and greater than the rate for placebo) were dry mouth, decreased appetite, insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3–5), 11 (95% CI 8–17), 11 (95% CI 8–18) and 19 (95% CI 11–75), respectively.
Conclusions LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week. Effect sizes were highly robust. Pending clinical trials include a long-term study examining maintenance of efficacy.
Introduction
Lisdexamfetamine dimesylate (SPD489, LDX) is a central nervous system stimulant originally approved in 2007 for the treatment of attention deficit hyperactivity disorder (ADHD). On January 30, 2015, LDX received approval by the US Food and Drug Administration (FDA) for the treatment of moderate to severe binge eating disorder (BED).
BED is the most common eating disorder, with an estimated lifetime prevalence of 2.6% among US adults, more than the prevalence for bulimia and anorexia nervosa combined. Despite this, BED often goes unrecognised and untreated, in part because although binge eating was first described in 1959, it was not included as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders until the fifth edition (DSM-5), published in 2013. In the DSM-5 definition, BED is characterised by recurrent episodes of binge eating (eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstances and a sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. Binge episodes are also associated with eating rapidly, eating until feeling uncomfortably full, eating large amounts of food when not feeling physically hungry, eating alone because of feeling embarrassed by how much one is eating, and feeling disgusted with oneself, depressed or guilty afterwards. BED is distinguished from bulimia nervosa in that BED is not associated with regular compensatory behaviours such as purging or excessive exercise, or with dietary restriction, although frequent dieting may be reported. Since binge eating is often a secretive behaviour, and commonly associated with a high degree of embarrassment or shame, it is not ordinarily revealed unless the clinician makes a direct inquiry regarding eating patterns. In addition to physical comorbidities including obesity and metabolic syndrome (although many persons with BED are not obese), BED is commonly associated with other psychiatric disorders, including anxiety, depression, impulse control disorders and substance use. Approximately 4 of 5 adults with lifetime BED have at least one comorbid psychiatric disorder, and approximately 1 of 2 has three or more. BED is actively researched, with over 1600 publications listed in the US National Library of Medicine's PubMed resource containing the text words 'binge eating disorder', together with over 220 clinical trials registered in the US ClinicalTrials.gov registry. Psychological treatments including cognitive behavioural interventions have been recommended as first line and are supported by meta-analytic reviews. Unfortunately, routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED, and up to now there have not been any approved pharmacological interventions for this disorder.
The aim of this review is to synthesise the available data regarding the efficacy and safety of LDX for the treatment of BED and to place this new treatment option into clinical perspective.
