-
Synapse (New York, N.Y.) May 1999Phentermine produces a spectrum of concentration-dependent biochemical effects. It interacts with NE transporters at 0.1 microM, DA transporters at about 1 microM, 5-HT...
Phentermine produces a spectrum of concentration-dependent biochemical effects. It interacts with NE transporters at 0.1 microM, DA transporters at about 1 microM, 5-HT transporters at 15 microM and MAO-A at about 100 microM. When administered at typical anorectic doses, phentermine primarily interacts with DA and NE transporters and does not produce biochemical or neurochemical effects which would occur if it were inhibiting MAO-A. Some other explanation other than MAO inhibition must be sought to explain how oral phentermine increases platelet 5-HT, since platelet MAO-B does not metabolize platelet 5-HT, and since amphetamine-type drugs are even weaker inhibitors of MAO-B than MAO-A. Clinical studies in humans have shown that amphetamine, which is a more potent inhibitor of MAO-A than phentermine, does not inhibit MAO-A at therapeutic doses. Neither phentermine alone, fluoxetine alone or their combined use have been associated with cardiac valvulopathy, and clinical experience has shown their combined use to be free of significant adverse effects. Viewed collectively, there appears to be no data to support the hypothesis that phentermine inhibits MAO at typical therapeutic doses.
Topics: Adrenergic Uptake Inhibitors; Brain Chemistry; Humans; Monoamine Oxidase Inhibitors; Phentermine; Serotonin
PubMed: 10231134
DOI: 10.1002/(SICI)1098-2396(199905)32:2<141::AID-SYN8>3.0.CO;2-R -
Clinical Pharmacology and Therapeutics Jan 2014Obesity is a growing pandemic, and related health and economic costs are staggering. Pharmacotherapy, partnered with lifestyle modifications, forms the core of current... (Review)
Review
Obesity is a growing pandemic, and related health and economic costs are staggering. Pharmacotherapy, partnered with lifestyle modifications, forms the core of current strategies to reduce the burden of this disease and its sequelae. However, therapies targeting weight loss have a significant history of safety risks, including cardiovascular and psychiatric events. Here, evolving strategies for developing antiobesity therapies, including targets, mechanisms, and developmental status, are highlighted. Progress in this field is underscored by Belviq (lorcaserin) and Qsymia (phentermine/topiramate), the first agents in more than 10 years to achieve regulatory approval for chronic weight management in obese patients. On the horizon, novel insights into metabolism and energy homeostasis reveal guanosine 3',5'-cyclic monophosphate (cGMP) signaling circuits as emerging targets for antiobesity pharmacotherapy. These innovations in molecular discovery may elegantly align with practical off-the-shelf approaches, leveraging existing approved drugs that modulate cGMP levels for the management of obesity.
Topics: Animals; Anti-Obesity Agents; Benzazepines; Drug Combinations; Drug Delivery Systems; Drug Discovery; Fructose; Humans; Obesity; Phentermine
PubMed: 24105257
DOI: 10.1038/clpt.2013.204 -
Journal of the American Association of... Oct 2017To review the currently available pharmacotherapies for obesity management with a particular focus on the United States. (Review)
Review
BACKGROUND AND PURPOSE
To review the currently available pharmacotherapies for obesity management with a particular focus on the United States.
METHODS
Narrative review based on literature searches and the latest prescribing information (up to July 2017).
CONCLUSIONS
Obesity pharmacotherapies may assist those individuals who have obesity, or overweight with comorbidities, who have failed to maintain weight loss with lifestyle modifications alone (caloric restriction and increased physical activity). Currently approved options in the United States include phentermine for short-term use and five obesity pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an obesity pharmacotherapy is indicated, treatment should be selected to provide the most appropriate option for each individual and their circumstances. Variables such as contraindications, individual comorbidities, patient choice, patient readiness to incorporate additional behavioral changes (e.g., alcohol prohibition), and cost should guide choices.
IMPLICATIONS FOR PRACTICE
Each of the obesity pharmacotherapies has advantages and disadvantages that can help guide treatment choice. Those receiving treatment may also have individual preferences based on factors such as administration route, frequency of dosing, and/or safety profile. In addition, some options may be particularly appropriate for patients with common obesity-related complications such as depression or diabetes.
Topics: Adult; Anti-Obesity Agents; Benzazepines; Female; Humans; Lactones; Liraglutide; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Risk Reduction Behavior; United States
PubMed: 29024552
DOI: 10.1002/2327-6924.12519 -
Synapse (New York, N.Y.) Dec 2000The anorectic drug phentermine produces dose-related toxic effects on brain dopamine (DA) neurons in animals. Until recently, phentermine was widely used in combination...
The anorectic drug phentermine produces dose-related toxic effects on brain dopamine (DA) neurons in animals. Until recently, phentermine was widely used in combination with fenfluramine for purposes of appetite suppression and weight loss. With the recent withdrawal of fenfluramine from the market, many people have begun combining phentermine with fluoxetine, a serotonin reuptake inhibitor which also produces mild anorectic effects. Fluoxetine, in addition to inhibiting serotonin reuptake, inhibits hepatic mixed function oxidase, which plays an important role in the metabolic degradation of amphetamines. The purpose of the present study was to assess the effects of fluoxetine on the anorectic and DA neurotoxic effects of phentermine in mice. Phentermine, in combination with fluoxetine, produced greater reductions in food intake and body weight than phentermine alone. The phentermine/fluoxetine combination also produced greater long-term reductions in brain DA levels than phentermine alone, likely reflecting greater DA neurotoxicity of the drug combination. Brain concentrations of phentermine were also found to be higher in animals pretreated with fluoxetine. These findings indicate that fluoxetine potentiates both the anorectic and DA neurotoxic effects of phentermine, probably by increasing phentermine brain levels. The clinical significance of these findings remains to be ascertained.
Topics: Animals; Anorexia; Appetite Depressants; Biogenic Monoamines; Body Temperature; Body Weight; Brain; Dopamine Antagonists; Eating; Fluoxetine; Liver; Male; Mice; Oxidoreductases; Phentermine; Time Factors
PubMed: 11044894
DOI: 10.1002/1098-2396(20001215)38:4<471::AID-SYN12>3.0.CO;2-6 -
The International Journal of Eating... Feb 2020Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized controlled trials (RCTs) yet performed, this trial aimed to evaluate PHEN/TPM-ERs efficacy and safety in a crossover RCT for patients with binge-eating disorder (BED) or bulimia nervosa (BN).
METHOD
Participants were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug washout, then 12-week crossover. Demographics, vitals, eating disorder behaviors, mood, and side effects were measured. Primary outcome was objective binge-eating (OBE) days/4-weeks; secondary outcomes included binge abstinence. Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis.
RESULTS
The 22 adults (BED = 18, BN = 4) were female (96%), Caucasian (55%), aged 42.9 (SD = 10.1) years with body mass index = 31.1 (SD = 6.2) kg/m . Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < .0001), with abstinence rates = 63.6% on PHEN/TPM-ER versus 9.1% on placebo (p < .0001). Weight changes = -5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo. Drop-out = 2 (9%) on PHEN/TPM-ER and 2 (9%) on placebo, with few side effects. Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo. Responses were not significantly different for BED versus BN.
DISCUSSION
This first RCT to evaluate the efficacy and safety of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective at reducing binge eating than placebo and well tolerated. However, with only four participants with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution.
TRIAL REGISTRATION
Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.
Topics: Adolescent; Adult; Binge-Eating Disorder; Bulimia Nervosa; Cross-Over Studies; Drug Combinations; Female; Humans; Middle Aged; Phentermine; Topiramate; Young Adult
PubMed: 31721257
DOI: 10.1002/eat.23192 -
Current Diabetes Reports May 2017This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate,... (Review)
Review
PURPOSE OF REVIEW
This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice.
RECENT FINDINGS
Weight loss achieved by currently approved drugs ranges from approximately 3 to 9%, above and beyond weight loss with lifestyle counseling alone, after a year. Response and attrition rates in clinical trials indicate that the benefits of pharmacotherapy range from substantial for some patients, modest for others, and no benefits for others still. Decisions regarding selection of a suitable drug from the available pharmacotherapy options and duration of treatment should be based on the expected and observed benefit-to-risk balance and tailored to the needs of each individual patient using the principles of shared decision-making.
Topics: Anti-Obesity Agents; Benzazepines; Clinical Trials as Topic; Fructose; Humans; Life Style; Liraglutide; Obesity; Phentermine; Topiramate; Weight Loss
PubMed: 28378293
DOI: 10.1007/s11892-017-0859-2 -
Singapore Medical Journal Sep 2017
Topics: Acetylcholine; Adult; Angina, Unstable; Central Nervous System Stimulants; Coronary Angiography; Coronary Vasospasm; Female; Humans; Patient Safety; Phentermine; Risk Factors
PubMed: 28261741
DOI: 10.11622/smedj.2017014 -
Obesity (Silver Spring, Md.) May 2017To assess the short-term tolerability of lorcaserin alone or with two dose regimens of phentermine. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess the short-term tolerability of lorcaserin alone or with two dose regimens of phentermine.
METHODS
This was a 12-week, randomized, double-blind, pilot safety study of N = 238 nondiabetic patients with obesity or overweight with ≥1 comorbidity randomized to lorcaserin 10 mg twice daily (BID; LOR BID) alone or with phentermine 15 mg once daily (QD; LOR BID+PHEN QD) or 15 mg twice daily (LOR BID+PHEN BID). Patients reporting ≥ 1 of 9 potentially serotonergic adverse events (AEs), mean weight loss (WL), and ≥5% WL are reported.
RESULTS
N = 238 were randomized, and N = 235 were treated. N = 94 reported potentially serotonergic AEs: 37.2% LOR BID, 42.3% LOR BID+PHEN QD, and 40.5% LOR BID+PHEN BID. AEs leading to discontinuation were reported approximately twice as often in the LOR BID+PHEN BID group versus the LOR BID group. Mean WL was 3.5 kg/3.3%, 7.0 kg/6.7%, and 7.6 kg/7.2% for LOR BID, LOR BID+PHEN QD, and LOR BID+PHEN BID, respectively. At least 5% WL was achieved by 28.2% LOR BID, 59.0% LOR BID+PHEN QD (P = 0.0002 vs. LOR BID), and 70.9% LOR BID+PHEN BID (P < 0.0001 vs. LOR BID) patients.
CONCLUSIONS
Phentermine added to lorcaserin enhanced short-term weight loss but did not increase incidence of potentially serotonergic AEs; however, phentermine twice daily increased discontinuation compared to both lorcaserin alone and lorcaserin plus phentermine once daily.
Topics: Adolescent; Adult; Anti-Obesity Agents; Benzazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Phentermine; Pilot Projects; Weight Loss; Young Adult
PubMed: 28440045
DOI: 10.1002/oby.21811 -
Diabetes Apr 2019Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the...
Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia. There is significant interest in combination use of liraglutide and phentermine for weight loss; however, both drugs have been reported to induce systemic hemodynamic changes, and as such the therapeutic window for this drug combination needs to be determined. To understand their impact on metabolic and cardiovascular physiology, we tested the effects of these drugs alone and in combination for 21 days in lean and obese male mice. The combination of liraglutide and phentermine, at 100 μg/kg/day and 10 mg/kg/day, respectively, produced the largest reduction in body weight in both lean and diet-induced obese (DIO) mice, when compared with both vehicle and monotherapy-treated mice. In lean mice, combination treatment at the aforementioned doses significantly increased heart rate and reduced blood pressure, whereas in DIO mice, combination therapy induced a transient increase in heart rate and decreased blood pressure. These studies demonstrate that in obese mice, the combination of liraglutide and phentermine may reduce body weight but only induce modest improvements in cardiovascular functions. Conversely, in lean mice, the additional weight loss from combination therapy does not improve cardiovascular parameters.
Topics: Animals; Anti-Obesity Agents; Blood Pressure; Body Weight; Drug Therapy, Combination; Heart Rate; Liraglutide; Male; Mice; Obesity; Phentermine; Treatment Outcome; Weight Loss
PubMed: 30674622
DOI: 10.2337/db18-1149 -
Newsweek Sep 1997
Topics: Antidepressive Agents, Second-Generation; Appetite Depressants; Consumer Product Safety; Fenfluramine; Fluoxetine; Heart Valve Diseases; Humans; Obesity; Phentermine; Risk Factors; United States; Weight Loss
PubMed: 10173270
DOI: No ID Found