Lisdexamfetamine for Binge Eating Disorder in Adults
Lisdexamfetamine for Binge Eating Disorder in Adults
Short-term treatment with LDX for BED produces robust therapeutic effects. A possible explanation rests with current thinking regarding pathologic overeating and its neurobiological underpinnings involving dysfunction of dopamine and norepinephrine circuitry. This is consistent with LDX's effect on dopamine and norepinephrine neurotransmitters. In addition to changes in actual binge eating frequency, there is evidence that LDX treatment impacts on binge eating associated obsessive and compulsive features.
Although psychological treatments such as cognitive behavioural therapy and interpersonal therapy can reduce binge eating behaviour, access to such treatments may be limited because of local availability and/or cost. Moreover, psychological treatment approaches have generally not resulted in weight loss, although successfully eliminating binge eating might protect against future weight gain.
Much effort has been made in the development of pharmacological approaches for the treatment of BED. Each alternative appeared to have a significant shortcoming, for example, although antidepressants can reduce the frequency of binge eating behaviour, they are not efficacious regarding weight loss, and although topiramate has efficacy in terms of both amelioration of binge eating and weight reduction, it has a negative impact on cognitive function.
Several limitations to this systematic review need to be made explicit. Available so far are the results of carefully conducted registration trials that enrolled subjects who fulfilled restrictive inclusion/exclusion criteria. Such patients may differ from persons encountered in routine clinical practice. For example, registration trials ordinarily exclude patients with current comorbid substance use disorders, untreated medical conditions, current suicidality, or who require concomitant use of other psychotropic agents. Moreover, adherence to treatment in a clinical trial is enhanced compared with less structured settings. Thus, pragmatic clinical trials that are more generalisable will help place LDX into clinical perspective for its use in the 'real world.' However by controlling who can participate in the registration trials, the potential confounding effects because of depression, anxiety, or ADHD can be minimised. Disentangling these different effects of LDX may be challenging in comorbid populations.
The studies themselves rely on self-reported diaries for the primary outcome measure. This is a potential weakness but unavoidable in an illness defined by the frequency of binge eating episodes. However, several secondary measures have clearly supported the primary findings.
The anorectic effect of LDX requires further characterisation, including whether or not dose–response for weight loss differs from that for reducing binge eating behaviours. It would also be useful to calculate the proportion of obese patients receiving LDX vs. placebo who experience a 5% and 10% decrease in their body weight in order to indirectly compare LDX with other agents on this outcome. However, LDX is not indicated for weight loss and the product label warns that the use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events.
Long-term data are anticipated, including a 52-week open-label extension to the short-term studies (NCT01657019). This will inform clinicians regarding the tolerability and safety profile of extended use of LDX in BED. Also pending are the results of a maintenance of efficacy study of LDX for BED, where time to relapse of binge eating is the primary outcome measure (NCT02009163). Practice-based evidence from medication utilisation databases will inform regarding typical doses used for LDX for the treatment of BED and whether dose adjustments are required over time. Whether the effect of LDX on BED is generalisable to other stimulants requires further research.
Discussion
Short-term treatment with LDX for BED produces robust therapeutic effects. A possible explanation rests with current thinking regarding pathologic overeating and its neurobiological underpinnings involving dysfunction of dopamine and norepinephrine circuitry. This is consistent with LDX's effect on dopamine and norepinephrine neurotransmitters. In addition to changes in actual binge eating frequency, there is evidence that LDX treatment impacts on binge eating associated obsessive and compulsive features.
Although psychological treatments such as cognitive behavioural therapy and interpersonal therapy can reduce binge eating behaviour, access to such treatments may be limited because of local availability and/or cost. Moreover, psychological treatment approaches have generally not resulted in weight loss, although successfully eliminating binge eating might protect against future weight gain.
Much effort has been made in the development of pharmacological approaches for the treatment of BED. Each alternative appeared to have a significant shortcoming, for example, although antidepressants can reduce the frequency of binge eating behaviour, they are not efficacious regarding weight loss, and although topiramate has efficacy in terms of both amelioration of binge eating and weight reduction, it has a negative impact on cognitive function.
Several limitations to this systematic review need to be made explicit. Available so far are the results of carefully conducted registration trials that enrolled subjects who fulfilled restrictive inclusion/exclusion criteria. Such patients may differ from persons encountered in routine clinical practice. For example, registration trials ordinarily exclude patients with current comorbid substance use disorders, untreated medical conditions, current suicidality, or who require concomitant use of other psychotropic agents. Moreover, adherence to treatment in a clinical trial is enhanced compared with less structured settings. Thus, pragmatic clinical trials that are more generalisable will help place LDX into clinical perspective for its use in the 'real world.' However by controlling who can participate in the registration trials, the potential confounding effects because of depression, anxiety, or ADHD can be minimised. Disentangling these different effects of LDX may be challenging in comorbid populations.
The studies themselves rely on self-reported diaries for the primary outcome measure. This is a potential weakness but unavoidable in an illness defined by the frequency of binge eating episodes. However, several secondary measures have clearly supported the primary findings.
The anorectic effect of LDX requires further characterisation, including whether or not dose–response for weight loss differs from that for reducing binge eating behaviours. It would also be useful to calculate the proportion of obese patients receiving LDX vs. placebo who experience a 5% and 10% decrease in their body weight in order to indirectly compare LDX with other agents on this outcome. However, LDX is not indicated for weight loss and the product label warns that the use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events.
Long-term data are anticipated, including a 52-week open-label extension to the short-term studies (NCT01657019). This will inform clinicians regarding the tolerability and safety profile of extended use of LDX in BED. Also pending are the results of a maintenance of efficacy study of LDX for BED, where time to relapse of binge eating is the primary outcome measure (NCT02009163). Practice-based evidence from medication utilisation databases will inform regarding typical doses used for LDX for the treatment of BED and whether dose adjustments are required over time. Whether the effect of LDX on BED is generalisable to other stimulants requires further research.
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