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Richard B. Rothman - One of the best experts on this subject based on the ideXlab platform.

  • Neurochemical mechanisms of Phentermine and fenfluramine : Therapeutic and adverse effects
    Drug Development Research, 2020
    Co-Authors: Richard B. Rothman, Michael H. Baumann
    Abstract:

    Most clinically available anorectic medications, such as Phentermine and fenfluramine, are thought to interact with monoamine systems in the brain. Preclinical evidence suggests that there is substantial overlap between the neural circuits controlling feeding behavior and those involved in self-administration of abused drugs. Thus, anorectics may be effective treatments for substance use disorders. The purpose of the present article is to review recent findings that address the neurochemical mechanisms of action of Phentermine, fenfluramine, the Phentermine plus fenfluramine combination, and other selected anorectic medications. We review studies that have examined the effects of Phentermine and fenfluramine in a variety of preclinical models of stimulant addiction. The implications of these findings for explaining the therapeutic efficacy and potential adverse actions of these drugs are considered. Finally, the review concludes by discussing the feasibility of developing novel drugs that produce the same neurochemical effects as Phentermine plus fenfluramine, without the associated adverse effects of primary pulmonary hypertension (fenfluramine-related), neurotoxicity (fenfluramine-related), and abuse liability (Phentermine-related). Such agents would have potential applications in the treatment of obesity, drug dependence, and other psychiatric disorders. Drug Dev. Res. 51:52–65, 2000. Published 2000 Wiley-Liss, Inc.

  • Phentermine therapy for obesity does not elevate blood pressure.
    Diabetes Obesity and Metabolism, 2011
    Co-Authors: E. J. Hendricks, Richard B. Rothman
    Abstract:

    To the Editor: The report by Kang et al. [1] of a clinical trial with a new diffuse-controlled release of Phentermine for obesity is timely because Phentermine is currently one of the few remaining approved drugs for obesity pharmacotherapy. We agree that the study data supports the authors’ conclusions that this formulation of Phentermine is a safe and effective treatment adjunct for treating obesity. We also agree that further longterm studies of Phentermine should be undertaken. In our opinion, Phentermine pharmacotherapy for obesity is much safer than is commonly assumed. Phentermine offers a high potential of substantial benefit to obese patients, particularly those with moderate elevations of blood pressure, and it should be the first choice medicine when pharmacotherapy is considered for most obese patients. Kang et al. mentioned that Phentermine may elevate blood pressure, even though they observed the opposite effect. Other than a few anecdotes, there is little or no evidence in the peer-reviewed medical literature to support the often repeated conjecture that Phentermine, when chronically administered, can elevate blood pressure. The clinical trial reports cited by Kang et al. either did not report blood pressures or reported that Phentermine-treated subjects had declines in blood pressure. The meta-analyses cited discuss elevations of blood pressure as adverse effects but provide no supporting data. Average blood pressures are known to decline when obese patients lose weight without pharmacotherapy [2]. Obesity treatment specialists experienced with Phentermine have known for some time that average blood pressures also decline in patients when Phentermine is added to weight loss therapy. These observations have recently been confirmed in two observational reports from private practices, one short term [3] and the other long term [4]. In clinical trials for Qnexa, a combination of Phentermine and topiramate, investigators also observed that the blood pressure declined in treated patients with the most pronounced declines occurring in patients with preexisting hypertension [5]. The long-term Phentermine study mentioned above [4] found that Phentermine-treated patients with preexisting hypertension had the greatest declines in blood pressure, patients with preexisting prehypertension had lesser declines, while patients with initial optimum blood pressures (

  • RE: Pulmonary hypertension associated with use of Phentermine?
    Yonsei Medical Journal, 2011
    Co-Authors: Ed J Hendricks, Richard B. Rothman
    Abstract:

    Dear Sir, Recently Bang, et al.1 reported a case of a 29 year-old obese woman who was hospitalized with pulmonary arterial hypertension (PAH) and a history of having taken Phentermine hydrochloride 37.5 milligrams daily for 35 days. Since common etiologies of PAH were excluded by the patient's history, examination procedures, and hospital course, the authors suggest this is the first case of Phentermine-induced PAH. We suggest instead this is a case of idiopathic pulmonary arterial hypertension (IPAH) rather than PAH secondary to therapeutic Phentermine. The authors suggest, based on one case report, that Phentermine mono-therapy produces the same increase in incidence of PAH previously seen in patients treated with fenfluramine mono-therapy and in patients treated with a combination of fenfluramine and Phentermine. However, a survey of 95 European cases of PAH by Abenhaim, et al.2 found that of the 30 patients that had a history of taking anorexic agents, 24 had taken a fenfluramine, but none had taken Phentermine. Moreover, Rich, et al.,3 in a North American prospective study in which 579 patients with pulmonary hypertension were studied, found that the odds ratios for an association of pulmonary hypertension and fenfluramine to be 7.5, an odds ratio for a similar association for Phentermine of 0.6, and concluded that fenfluramines, but not Phentermine are risk factors for PAH. Since fenfluramines were taken off-market in 1997 there have been no subsequent reports linking PAH or IPAH to anorectic medicines. Hence the literature does not support the contention of Bang, et al. that Phentermine mono-therapy has caused an increased incidence of secondary PAH similar to that caused by fenfluramine. Physicians in other countries may not be aware that Phentermine has long been the most widely used anti-obesity medicine in the United States. A recent survey of United States obesity treatment specialists found that for 97%, Phentermine was their first choice among the available anti-obesity drugs.4 The majority of physicians surveyed reported they prescribed Phentermine long-term in any patient provided the medicine was effective and produced no intolerable side effects. The longest duration of Phentermine therapy reported in the literature has been forty years with no serious adverse effects.5 The survey confirmed that most specialists have employed doses higher than the maximum dose of 37.5 milligrams daily recommended by the U.S. Food and Drug Administration (FDA)-approved label. There are other reports of the safe use of higher doses.4,6-9 Thus, in spite of continued widespread use of Phentermine for longer durations and higher doses than recommended by the FDA-approved label, there is no report of an increased incidence of pulmonary hypertension due to Phentermine in the U.S. The incidence of IPAH is approximately one case per million per year in the general population. Since Phentermine is so widely used, it is reasonable to expect an occasional patient diagnosed with IPAH will coincidently have taken Phentermine. PAH and IPAH are characterized by an increase in pulmonary vascular resistance due to progressive obliteration of pulmonary arterioles, which in turn are induced by pulmonary arteriole smooth muscle cell proliferation and arteriolar vasoconstriction with accompanying inflammation and thrombosis. One hypothesis to explain fenfluramine-induced PAH is that fenfluramine releases 5-hydroxytryptophan (5-HT) via the 5-HT transporter (SERT), and that the increased concentration of plasma 5-HT provokes pulmonary vasoconstriction and pulmonary arterial smooth muscle cell proliferation.10 However, recent data raises questions about this hypothesis.11 5-HT is also thought to play a central role in the pathogenesis of IPAH. Bang, et al. imply that Phentermine is active as a serotonin transporter producing increases in 5-HT levels, and therefore has the potential to cause PAH. However, Rothman, et al.12 have shown previously that Phentermine has considerably less potent SERT substrate activity, and is considerably less effective in elevating plasma 5-HT compared to fenfluramine, and compared to the commonly abused stimulants methamphetamine and 3,4-methylenedioxymethamphetamine. In another study Rothman, et al. found that Phentermine produced minimal increases in 5HT, insufficient to provoke pulmonary arteriolar smooth muscle proliferation.13 These studies suggest that it is unlikely Phentermine could induce PAH by the mechanism proposed by Bang, et al. In summary we suggest that Phentermine, after 52 years of widespread use has proven to be both effective and safe. Historically, an association between Phentermine mono-therapy and PAH has been suggested but confirming evidence has not appeared. Currently, while we have few effective pharmacologic agents to include in obesity treatment, patients and physicians are fortunate to have Phentermine available. Bang, et al. are correct in noting the absence of 870long-term, dose ranging, clinical trials with Phentermine; we concur that such trials are needed and should be conducted. Meanwhile, while we await trials, Phentermine treatment should not be withheld from the obese because of fear of theoretical but unproven adverse effects.

  • Phentermine cardiovascular safety II: Response to Yosefy Int J Cardiol. 2009 Epub Mar 19
    International Journal of Cardiology, 2010
    Co-Authors: Richard B. Rothman, Ed J Hendricks
    Abstract:

    Abstract This is the fourth in a series of letters-to-the-editor discussing Phentermine and cardiovascular safety. Yosefy et al., in reporting a case of aortic cusp tear in a 28year-old woman with a bicuspid aortic valve, attributed the tear to previous Phentermine therapy. Evidence of mitral and tricuspid valve thickening was noted at echocardiography. In replying we pointed out that Phentermine-induced valvular heart disease has not been reported and suggested that, since the reference cited for support referred to fenfluramine-induced valvulopathy, the attribution of the cusp tear to Phentermine was incorrect. Yosefy replied, asserting that since the patient had no other cardiac risk factor, the tear had to be due to Phentermine. In support of his presumption that Phentermine therapy can induce cardiac risk he cited only the PDR warnings for Phentermine. In this reply we point out that a congenital biscupid valve should not be ignored as a cardiac risk factor, that aortic valve cusp tears have been associated with bicuspid valves but never with Phentermine or with valve thickening no matter the etiology, and that there is no published data implicating Phentermine as a cause of valve thickening (or any other valve pathology). Evidence of Phentermine safety in the peer-reviewed medical literature is discussed in the context of the cardiovascular warnings for Phentermine in the PDR.

  • Phentermine cardiovascular safety
    American Journal of Emergency Medicine, 2009
    Co-Authors: Richard B. Rothman, Ed J Hendricks
    Abstract:

    A letter to the editor from Yosefy et al. [1] in the International Journal of Cardiology recently came to our attention in which the authors state “Phentermine is known to cause valvular disease with prolonged use” and cite for support of this statement a paper by Sachdev et al. [2]. The statement is incorrect, is not supported by the cited reference, and should be refuted since it incorrectly maligns a drug of known safety and usefulness in treating obesity [3]. Furthermore the cited reference pertains to fenfluramineinduced rather than Phentermine-induced valvulopathy. Current evidence indicates that Phentermine can reduce risk factors for cardiac disease since Phentermine therapy included in a comprehensive weight loss program produces an enhanced weight loss [4]. Among the obesity drugs, only the fenfluramines cause drug-induced cardiac valvulopathy [5,6]. Valvulopathic drugs, including fenfluramines, ergotamine, methysergide, pergolide, and cabergoline, are known to induce damage because they are potent agonists of cardiac 5-HT2B receptors [7,8]. Phentermine is not a serotonergic drug and it does not induce cardiac valvulopathy [9]. Obesity is a known risk factor for cardiovascular pathology including obesity cardiomyopathy, venous insufficiency, venous thrombosis, pulmonary embolization, hypertension, stroke, coronary artery disease, congestive heart failure, and arrhythmias [10–12]. Phentermine has consistently been the most frequently prescribed anti-obesity medication [13]. A recent survey of 250 U.S. physicians practicing bariatric

Richard J. Wurtman - One of the best experts on this subject based on the ideXlab platform.

  • characterization of Phentermine and related compounds as monoamine oxidase mao inhibitors
    Biochemical Pharmacology, 2000
    Co-Authors: Ismail H. Ulus, Timothy J. Maher, Richard J. Wurtman
    Abstract:

    Abstract Phentermine was shown in the 1970s to inhibit the metabolism of serotonin by monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence, it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. We examined the effects of Phentermine and several other unlabeled MAO inhibitors on MAO activities in rat lung, brain, and liver, and also the interactions of such drugs when administered together. Rat tissues were assayed for MAO-A and -B, using serotonin and β-phenylethylamine as substrates. Phentermine inhibited serotonin-metabolizing (MAO-A) activity in all three tissues with Ki values of 85–88 μM. These potencies were similar to those of the antidepressant MAO inhibitors iproniazid and moclobemide. When Phentermine was mixed with other unlabeled reversible MAO inhibitors (e.g. pseudoephedrine, ephedrine, norephedrine; estradiol benzoate), the degree of MAO inhibition was additive. The cardiac valvular lesions and primary pulmonary hypertension that have been reported to be associated with fenfluramine-Phentermine use may have resulted from the intermittent concurrent blockage of both serotonin uptake and metabolism.

  • Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramines
    The Lancet, 1999
    Co-Authors: Timothy J. Maher, Ismail H. Ulus, Richard J. Wurtman
    Abstract:

    1It was suggested that these findings, were due to an increase in circulating serotonin. Subsequently, the US Food and Drug Administration found heart-valve lesions among patients taking a fenfluramine without Phentermine. Given the paucity of data on Phentermine’s actions, we determined whether Phentermine could modify the metabolism of other monoamines besides the norepinephrine released from sympathetic neurons. In rats, Phentermine, like d-amphetamine, releases dopamine into brain synapses. 2 We tested the ability of a low dose (15 mg by mouth) to affect plasma dopamine in human beings. Nine young, non-obese male volunteers gave blood just before, and 1, 2, or 4 h after receiving the drug. Plasma dopamine concentrations, assayed by radioimmunoassay 3 , rose with Phentermine (p

  • Phentermine and other monoamine oxidase inhibitors may increase plasma serotonin when given with fenfluramines
    The Lancet, 1999
    Co-Authors: Timothy J. Maher, Ismail H. Ulus, Richard J. Wurtman
    Abstract:

    1It was suggested that these findings, were due to an increase in circulating serotonin. Subsequently, the US Food and Drug Administration found heart-valve lesions among patients taking a fenfluramine without Phentermine. Given the paucity of data on Phentermine’s actions, we determined whether Phentermine could modify the metabolism of other monoamines besides the norepinephrine released from sympathetic neurons. In rats, Phentermine, like d-amphetamine, releases dopamine into brain synapses. 2 We tested the ability of a low dose (15 mg by mouth) to affect plasma dopamine in human beings. Nine young, non-obese male volunteers gave blood just before, and 1, 2, or 4 h after receiving the drug. Plasma dopamine concentrations, assayed by radioimmunoassay 3 , rose with Phentermine (p<0·05; ANOVA; Wilcoxon’s test); however a greater increase was noted in serotin levels within the blood platelets as assayed by ELISA and confirmed by high performance liquid chromatography (r=0·496; p<0·001). The increase in platelet serotonin could reflect increased release of serotonin from enterochromaffin cells, or inhibition of its metabolism by monoamine oxidase (MAO). That the increase resulted from MAO inhibition and not from increased serotonin release was shown by the finding that plasma serotonin concentration fell slightly. That Phentermine inhibits the MAO which catabolises serotonin was well known in the early 1970s,

  • effects of fenfluramine and Phentermine fen phen on dopamine and serotonin release in rat striatum in vivo microdialysis study in conscious animals
    Brain Research, 1998
    Co-Authors: Aygul Balcioglu, Richard J. Wurtman
    Abstract:

    Abstract We measured the effects of acute or chronic administration of fenfluramine and Phentermine, alone or in combination, on brain dopamine and serotonin release into striatal dialysates of freely moving rats. Samples collected every 30 min were assayed in a single run by high-pressure liquid chromatography. Acute or chronic administration of fenfluramine (1 mg/kg, i.p.) did not significantly change dopamine concentrations in rat striatal dialysates, but increased those of serotonin by 182% (acute) and 124% (chronic). Phentermine (2 mg/kg, i.p.), on the other hand, significantly increased dopamine concentrations by 52% (acute) and 80% (chronic) without affecting those of serotonin. Administration of the drugs in combination (fenfluramine 1 mg/kg and Phentermine 2 mg/kg) amplified the effects of each, increasing striatal dopamine concentrations by 209% (acute) and serotonin concentrations by 330% (acute) and 299% (chronic).

Ed J Hendricks - One of the best experts on this subject based on the ideXlab platform.

  • addiction potential of Phentermine prescribed during long term treatment of obesity
    International Journal of Obesity, 2014
    Co-Authors: Ed J Hendricks, Manit Srisurapanont, Stacy L Schmidt, M Haggard, S Souter, C L Mitchell, D G De Marco, M J Hendricks, Y Istratiy, Frank L Greenway
    Abstract:

    Phentermine was approved by the US FDA in 1959 for short term use for obesity. It is the most commonly used anti-obesity drug on the US market and many US bariatric physicians use Phentermine long term, ignoring the FDA guidelines that it be used for three months or less. Phentermine is not approved for use in Europe and some other countries around the world because of the fear of addiction, tachycardia, and elevated blood pressure. Actual objective assessments of Phentermine, as compared to administrative opinions, have been rare. The article by Hendricks et al in this issue is one of the few available in the literature. The study is not optimally designed, but suggests that fears of addiction to Phentermine are exaggerated. None of the 269 subjects who had been on Phentermine for up to 21 years demonstrated any addictive behavior as assessed by questionnaire and physical examination. Prior studies in the literature in monkeys did not demonstrate significant addictive potential. However, Phentermine has a reputation as a “street drug” and is sold in Europe for high prices. Since the combination of Phentermine and topiramate has just been approved for long term use in the US, government sponsored, well controlled research into the long term use of generic Phentermine is needed. There is no possibility that any private company will do long term research on this generic drug. Should the fears regarding Phentermine be shown to be groundless, the positions of governments to ban Phentermine should be reconsidered.

  • blood pressure and heart rate effects weight loss and maintenance during long term Phentermine pharmacotherapy for obesity
    Obesity, 2011
    Co-Authors: Ed J Hendricks, Frank L Greenway, Eric C Westman, Alok K Gupta
    Abstract:

    There is a perception that Phentermine pharmacotherapy for obesity increases blood pressure and heart rate (HR), exposing treated patients to increased cardiovascular risk. We collected data from Phentermine-treated (PT) and Phentermine-untreated (P0) patients at a private weight management practice, to examine blood pressure, HR, and weight changes. Records of 300 sequential returning patients were selected who had been treated with a low-carbohydrate ketogenic diet if their records included complete weight, blood pressure, and HR data from seven office examinations during the first 12 weeks of therapy. The mean time in therapy, time range, and mode was 92 (97.0), 12–624, and 52 weeks. 14% were normotensive, 52% were prehypertensive, and 34% were hypertensive at their first visit or had a previous diagnosis of hypertension. PT subjects systolic blood pressure/diastolic blood pressure (SBP/DBP) declined from baseline at all data points (SBP/DBP −6.9/−5.0 mm Hg at 26, and −7.3/−5.4 at 52 weeks). P0 subjects' declines of SBP/DBP at both 26 and 52 weeks were −8.9/−6.3 but the difference from the treated cohort was not significant. HR changes in treated/untreated subjects at weeks 26 (−0.9/−3.5) and 52 (+1.2/−3.6) were not significant. Weight loss was significantly greater in the PT cohort for week 1 through 104 (P = 0.0144). These data suggest Phentermine treatment for obesity does not result in increased SBP, DBP, or HR, and that weight loss assisted with Phentermine treatment is associated with favorable shifts in categorical blood pressure and retardation of progression to hypertension in obese patients.

  • RE: Pulmonary hypertension associated with use of Phentermine?
    Yonsei Medical Journal, 2011
    Co-Authors: Ed J Hendricks, Richard B. Rothman
    Abstract:

    Dear Sir, Recently Bang, et al.1 reported a case of a 29 year-old obese woman who was hospitalized with pulmonary arterial hypertension (PAH) and a history of having taken Phentermine hydrochloride 37.5 milligrams daily for 35 days. Since common etiologies of PAH were excluded by the patient's history, examination procedures, and hospital course, the authors suggest this is the first case of Phentermine-induced PAH. We suggest instead this is a case of idiopathic pulmonary arterial hypertension (IPAH) rather than PAH secondary to therapeutic Phentermine. The authors suggest, based on one case report, that Phentermine mono-therapy produces the same increase in incidence of PAH previously seen in patients treated with fenfluramine mono-therapy and in patients treated with a combination of fenfluramine and Phentermine. However, a survey of 95 European cases of PAH by Abenhaim, et al.2 found that of the 30 patients that had a history of taking anorexic agents, 24 had taken a fenfluramine, but none had taken Phentermine. Moreover, Rich, et al.,3 in a North American prospective study in which 579 patients with pulmonary hypertension were studied, found that the odds ratios for an association of pulmonary hypertension and fenfluramine to be 7.5, an odds ratio for a similar association for Phentermine of 0.6, and concluded that fenfluramines, but not Phentermine are risk factors for PAH. Since fenfluramines were taken off-market in 1997 there have been no subsequent reports linking PAH or IPAH to anorectic medicines. Hence the literature does not support the contention of Bang, et al. that Phentermine mono-therapy has caused an increased incidence of secondary PAH similar to that caused by fenfluramine. Physicians in other countries may not be aware that Phentermine has long been the most widely used anti-obesity medicine in the United States. A recent survey of United States obesity treatment specialists found that for 97%, Phentermine was their first choice among the available anti-obesity drugs.4 The majority of physicians surveyed reported they prescribed Phentermine long-term in any patient provided the medicine was effective and produced no intolerable side effects. The longest duration of Phentermine therapy reported in the literature has been forty years with no serious adverse effects.5 The survey confirmed that most specialists have employed doses higher than the maximum dose of 37.5 milligrams daily recommended by the U.S. Food and Drug Administration (FDA)-approved label. There are other reports of the safe use of higher doses.4,6-9 Thus, in spite of continued widespread use of Phentermine for longer durations and higher doses than recommended by the FDA-approved label, there is no report of an increased incidence of pulmonary hypertension due to Phentermine in the U.S. The incidence of IPAH is approximately one case per million per year in the general population. Since Phentermine is so widely used, it is reasonable to expect an occasional patient diagnosed with IPAH will coincidently have taken Phentermine. PAH and IPAH are characterized by an increase in pulmonary vascular resistance due to progressive obliteration of pulmonary arterioles, which in turn are induced by pulmonary arteriole smooth muscle cell proliferation and arteriolar vasoconstriction with accompanying inflammation and thrombosis. One hypothesis to explain fenfluramine-induced PAH is that fenfluramine releases 5-hydroxytryptophan (5-HT) via the 5-HT transporter (SERT), and that the increased concentration of plasma 5-HT provokes pulmonary vasoconstriction and pulmonary arterial smooth muscle cell proliferation.10 However, recent data raises questions about this hypothesis.11 5-HT is also thought to play a central role in the pathogenesis of IPAH. Bang, et al. imply that Phentermine is active as a serotonin transporter producing increases in 5-HT levels, and therefore has the potential to cause PAH. However, Rothman, et al.12 have shown previously that Phentermine has considerably less potent SERT substrate activity, and is considerably less effective in elevating plasma 5-HT compared to fenfluramine, and compared to the commonly abused stimulants methamphetamine and 3,4-methylenedioxymethamphetamine. In another study Rothman, et al. found that Phentermine produced minimal increases in 5HT, insufficient to provoke pulmonary arteriolar smooth muscle proliferation.13 These studies suggest that it is unlikely Phentermine could induce PAH by the mechanism proposed by Bang, et al. In summary we suggest that Phentermine, after 52 years of widespread use has proven to be both effective and safe. Historically, an association between Phentermine mono-therapy and PAH has been suggested but confirming evidence has not appeared. Currently, while we have few effective pharmacologic agents to include in obesity treatment, patients and physicians are fortunate to have Phentermine available. Bang, et al. are correct in noting the absence of 870long-term, dose ranging, clinical trials with Phentermine; we concur that such trials are needed and should be conducted. Meanwhile, while we await trials, Phentermine treatment should not be withheld from the obese because of fear of theoretical but unproven adverse effects.

  • a study of abrupt Phentermine cessation in patients in a weight management program
    American Journal of Therapeutics, 2011
    Co-Authors: Ed J Hendricks, Frank L Greenway
    Abstract:

    Phentermine is the most widely used antiobesity drug in the United States. Although no evidence of Phentermine addiction has been published, fear that Phentermine has addiction potential has contributed to curtailment of its worldwide use in clinical practice. The aim of this study was to evaluate the abuse and addiction potential of long-term Phentermine pharmacotherapy in patients in a weight management program. Thirty-five patients in a weight management program who abruptly stopped taking prescribed Phentermine on their own initiative were examined using the 18-item Kampman Cocaine Selective Severity Assessment scale modified for Phentermine. The Kampman Cocaine Selective Severity Assessment scale has also been modified by McGregor for amphetamines to assess withdrawal from amphetamine in amphetamine-addicted subjects. For comparison, 35 new patients were examined with the same scale before any treatment was initiated. Data from the treated and untreated groups were compared by t test with each other and with published data from amphetamine-addicted subjects. There were no significant differences in individual items or total scores between the patients who stopped Phentermine abruptly and the patients who had never taken Phentermine. There was a striking and significant difference in individual and total scores between the Phentermine-treated subjects and the amphetamine-dependent subjects. Cravings for the substance abused, the hallmark characteristic of substance dependence and withdrawal, were entirely absent in the Phentermine-treated subjects. Abrupt cessation of long-term Phentermine therapy does not induce amphetamine-like withdrawal. Long-term Phentermine therapy does not induce Phentermine cravings. Symptoms observed after abrupt Phentermine cessation represent loss of therapeutic effect and are not withdrawal.

  • Phentermine cardiovascular safety II: Response to Yosefy Int J Cardiol. 2009 Epub Mar 19
    International Journal of Cardiology, 2010
    Co-Authors: Richard B. Rothman, Ed J Hendricks
    Abstract:

    Abstract This is the fourth in a series of letters-to-the-editor discussing Phentermine and cardiovascular safety. Yosefy et al., in reporting a case of aortic cusp tear in a 28year-old woman with a bicuspid aortic valve, attributed the tear to previous Phentermine therapy. Evidence of mitral and tricuspid valve thickening was noted at echocardiography. In replying we pointed out that Phentermine-induced valvular heart disease has not been reported and suggested that, since the reference cited for support referred to fenfluramine-induced valvulopathy, the attribution of the cusp tear to Phentermine was incorrect. Yosefy replied, asserting that since the patient had no other cardiac risk factor, the tear had to be due to Phentermine. In support of his presumption that Phentermine therapy can induce cardiac risk he cited only the PDR warnings for Phentermine. In this reply we point out that a congenital biscupid valve should not be ignored as a cardiac risk factor, that aortic valve cusp tears have been associated with bicuspid valves but never with Phentermine or with valve thickening no matter the etiology, and that there is no published data implicating Phentermine as a cause of valve thickening (or any other valve pathology). Evidence of Phentermine safety in the peer-reviewed medical literature is discussed in the context of the cardiovascular warnings for Phentermine in the PDR.

D G Parkes - One of the best experts on this subject based on the ideXlab platform.

  • Antiobesity effects of the β-cell hormone amylin in combination with Phentermine or sibutramine in diet-induced obese rats
    International Journal of Obesity, 2008
    Co-Authors: J D Roth, J L Trevaskis, J Wilson, J Athanacio, C Mack, N C Kesty, T Coffey, C Weyer, D G Parkes
    Abstract:

    Objective: To characterize the interactive effects of amylin with Phentermine or sibutramine on food intake, body weight/composition and gene expression in diet-induced obese (DIO) rats. Design: DIO rats were intraperitoneally injected with a single dose of amylin (10 μg kg^−1) and/or Phentermine (1 mg kg^−1) or chronically infused with amylin (100 μg kg^−1 d^−1) or vehicle with or without Phentermine (0.5–10 mg kg^−1 d^−1) or sibutramine (3 mg kg^−1 d^−1) using two surgically implanted subcutaneous osmotic mini-pumps. Measurements: Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, Phentermine or amylin+Phentermine). Body weight and composition (for amylin and/or sibutramine or Phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (β-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or Phentermine) after sustained infusion (2 weeks). Results: Acute co-administration of amylin (10 μg kg^−1) and Phentermine (1 mg kg^−1) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain (∼4–8%). Phentermine's anorexigenic (10–17%) and weight-reducing effects (∼0–5%) were only evident at the highest dose tested (10 mg kg^−1 d^−1). Combination of amylin (100 μg kg^−1 d^−1) and Phentermine reduced food intake (30–43%), body weight (8–12%) and adiposity to a greater extent than either monotherapy. Amylin prevented Phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin+sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin+Phentermine treatment, amylin+sibutramine mediated weight loss was attributable to significant reductions in fat mass. Conclusions: Combined treatment of DIO rats with the pancreatic β-cell hormone amylin and Phentermine or sibutramine resulted in additive anorexigenic, weight- and fat-reducing effects.

  • antiobesity effects of the beta cell hormone amylin in combination with Phentermine or sibutramine in diet induced obese rats
    International Journal of Obesity, 2008
    Co-Authors: J D Roth, J L Trevaskis, J Athanacio, N C Kesty, T Coffey, C Weyer, J K Wilson, Christine M Mack, D G Parkes
    Abstract:

    To characterize the interactive effects of amylin with Phentermine or sibutramine on food intake, body weight/composition and gene expression in diet-induced obese (DIO) rats. DIO rats were intraperitoneally injected with a single dose of amylin (10 μg kg−1) and/or Phentermine (1 mg kg−1) or chronically infused with amylin (100 μg kg−1 d−1) or vehicle with or without Phentermine (0.5–10 mg kg−1 d−1) or sibutramine (3 mg kg−1 d−1) using two surgically implanted subcutaneous osmotic mini-pumps. Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, Phentermine or amylin+Phentermine). Body weight and composition (for amylin and/or sibutramine or Phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (β-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or Phentermine) after sustained infusion (2 weeks). Acute co-administration of amylin (10 μg kg−1) and Phentermine (1 mg kg−1) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain (∼4–8%). Phentermine's anorexigenic (10–17%) and weight-reducing effects (∼0–5%) were only evident at the highest dose tested (10 mg kg−1 d−1). Combination of amylin (100 μg kg−1 d−1) and Phentermine reduced food intake (30–43%), body weight (8–12%) and adiposity to a greater extent than either monotherapy. Amylin prevented Phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin+sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin+Phentermine treatment, amylin+sibutramine mediated weight loss was attributable to significant reductions in fat mass. Combined treatment of DIO rats with the pancreatic β-cell hormone amylin and Phentermine or sibutramine resulted in additive anorexigenic, weight- and fat-reducing effects.

Susan L Mcelroy - One of the best experts on this subject based on the ideXlab platform.

  • successful treatment of binge eating disorder with combination Phentermine topiramate extended release
    The Primary Care Companion To The Journal of Clinical Psychiatry, 2015
    Co-Authors: Anna I Guerdjikova, Angela Fitch, Susan L Mcelroy
    Abstract:

    To the Editor: Phentermine/topiramate extended release is a novel medication approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in obese adults. To our knowledge, Phentermine/topiramate extended release has not yet been evaluated in binge eating disorder, which often co-occurs with obesity. We therefore present 2 patients with binge eating disorder and obesity who experienced cessation of binge-eating behaviors and clinically significant weight loss with Phentermine/topiramate extended release.

  • Successful Treatment of Binge Eating Disorder With Combination Phentermine/Topiramate Extended Release.
    The Primary Care Companion To The Journal of Clinical Psychiatry, 2015
    Co-Authors: Anna I Guerdjikova, Angela Fitch, Susan L Mcelroy
    Abstract:

    To the Editor: Phentermine/topiramate extended release is a novel medication approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in obese adults. To our knowledge, Phentermine/topiramate extended release has not yet been evaluated in binge eating disorder, which often co-occurs with obesity. We therefore present 2 patients with binge eating disorder and obesity who experienced cessation of binge-eating behaviors and clinically significant weight loss with Phentermine/topiramate extended release.