Stimulants for the Control of Hedonic Appetite

Abstract

The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug.

The Obesity–Impulsivity Axis: Potential Metabolic Interventions in Chronic Psychiatric Patients

“…A striatal hypodopaminergic state is believed to trigger overnutrition, which in turn augments dopamine transmission. According to this model, D-2 stimulants correct the hypodopaminergia, lowering the overnutrition reward ( 100 – 102 ). Indeed, reduced D-2 receptor density was demonstrated in obese individuals, implying impaired dopaminergic signaling in this metabolic disorder ( 103 ).…”

The Neurobiology of Binge-eating Disorder Compared with Obesity: Implications for Differential Therapeutics

“…Stimulants have been used to treat obesity and, more recently, BED. Stimulants act on the reward system by increasing catecholamine availability via reversing transport systems, 152,153 which results in appetite suppression associated with elevated extracellular dopamine in the VS 154 and, importantly, dose-related improvements in executive functioning. 155 Appetite-suppressant effects of stimulant medications led to their early applications for weight loss in patients with obesity; for example, amphetamines were used to reduce appetite beginning in the 1930s, and the first stimulant to be FDA approved for treating obesity was methamphetamine in 1947.…”

Drug Treatment of Obesity: From Bench to Bedside

“…Modulators of monoamine neurotransmitters (dopamine, serotonin and norepinephrine) can suppress appetite efficiently by enhancing POMC neuronal activity [87]. However, a major concern for the use of this therapy is the risk of adverse cardiovascular events and psychiatric morbidity.…”