Addiction potential of phentermine prescribed during long-term treatment of obesity

Hendricks, Ed J.; Srisurapanont, Manit; Schmidt, Stacy L.; Haggard, Morgandy; Souter, S; Mitchell, CL; Marco, Dubini; Hendricks, Marcia; Istratiy, Y; Greenway, Frank L.

doi:10.1038/ijo.2013.74

Cited by 53 publications

(36 citation statements)

References 38 publications

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“…Evaluation of phentermine’s addictive potential revealed no abuse liability in overweight, obese and weight loss maintenance patients (Hendricks et al, 2014). Amphetamine-like withdrawal was absent upon abrupt treatment cessation at doses much higher than commonly recommended and after treatment durations of up to 21 years (Hendricks et al, 2014). …”

Section: Pharmacotherapies For Obesitymentioning

confidence: 99%

Obesity: Current and potential pharmacotherapeutics and targets

Narayanaswami

Dwoskin

2017

Pharmacology & Therapeutics

157

121

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Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed.

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Section: Pharmacotherapies For Obesitymentioning

confidence: 99%

Obesity: Current and potential pharmacotherapeutics and targets

Narayanaswami

Dwoskin

2017

Pharmacology & Therapeutics

157

121

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“…12 Neuropsychiatric related adverse events were also more common, including depression (7%, 33), anxiety (4%, 50), irritability (3%, 50), insomnia (10%, 20), and disturbances in attention (4%, 33). 12 Although phentermine-ER topiramate (15 and 92 mg/d, respectively) increases heart rate by about 2 beats/min, the FDA judged that the potential increase in cardiovascular risk was balanced by improvements in blood pressure and other cardiovascular risk factors.…”

Section: Phentermine-er Topiramatementioning

confidence: 99%

Pharmacotherapy for weight loss

Rueda-Clausen

Padwal

2014

BMJ

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“…Phentermine was approved as an anti-obesity agent by the FDA in 1959 for shortterm management [40] and was approved again when combined with topiramate in 2012 [40] . A recent study for long-term use has shown that phentermine is not associated with addiction and drug-craving behaviour [41] . Phentermine is not associated with serious risk, although high blood pressure due to vasoconstriction and vasculopathies has been reported [42] .…”

Section: Anti-obesity Drugs and Monoaminesmentioning

confidence: 99%

Khat (<b><i>Catha edulis</i></b>) and Obesity: A Scoping Review of Animal and Human Studies

et al. 2016

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Background: Khat (Catha edulis) is a plant that is deeply rooted in the cultural life of East African and Southwestern Arabian populations. Prevalent traditional beliefs about khat are that the plant has an effect on appetite and body weight. Summary: This review assesses the accumulated evidences on the mutual influence of monoamines, hormones and neuropeptides that are linked to obesity. A few anti-obesity drugs that exert their mechanisms of action through monoamines are briefly discussed to support the notion of monoamines being a critical target of drug discovery for new anti-obesity drugs. Subsequently, the review provides a comprehensive overview of central dopamine and serotonin changes that are associated with the use of khat or its alkaloids. Then, all the studies on khat that describe physical, biochemical and hormonal changes are summarised and discussed in depth. Conclusion: The reviewed studies provide relatively acceptable evidence that different khat extracts or cathinone produces changes in terms of weight, fat mass, appetite, lipid biochemistry and hormonal levels. These changes are more pronounced at higher doses and long durations of intervention. The most suggested mechanism of these changes is the central action that produces changes in the physiology of dopamine and serotonin. Nonetheless, there are a number of variations in the study design, including species, doses and durations of intervention, which makes it difficult to arrive at a final conclusion about khat regarding obesity, and further studies are necessary in the future to overcome these limitations.

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Addiction potential of phentermine prescribed during long-term treatment of obesity

Cited by 53 publications

References 38 publications

Obesity: Current and potential pharmacotherapeutics and targets

Obesity: Current and potential pharmacotherapeutics and targets

Pharmacotherapy for weight loss

Khat (<b><i>Catha edulis</i></b>) and Obesity: A Scoping Review of Animal and Human Studies

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