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Clinics (Sao Paulo, Brazil) May 2017The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A systematic review of primary studies was conducted, followed by a direct meta-analysis (random effect) and mixed treatment comparison. Medline and other databases were searched. Heterogeneity was explored through I2 associated with a p-value. Of 739 identified publications, 25 were included in the meta-analysis. The global evaluation of Cochrane resulted in 19 studies with a high level of bias and six with unclear risk. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.
Topics: Appetite Depressants; Diethylpropion; Humans; Mazindol; Obesity; Overweight; Publication Bias; Reproducibility of Results; Risk Factors; Treatment Outcome; Weight Loss
PubMed: 28591345
DOI: 10.6061/clinics/2017(05)10 -
BMJ Clinical Evidence Mar 2011About one third of the US population and one quarter of the UK population are obese, with increased risks of hypertension, dyslipidaemia, diabetes, cardiovascular... (Review)
Review
INTRODUCTION
About one third of the US population and one quarter of the UK population are obese, with increased risks of hypertension, dyslipidaemia, diabetes, cardiovascular disease, osteoarthritis, and some cancers. Fewer than 10% of overweight or obese adults aged 40 to 49 years revert to a normal body weight after 4 years. Nearly 5 million US adults used prescription weight-loss medication between 1996 and 1998, but one quarter of all users were not overweight.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in adults with obesity? What are the effects of bariatric surgery in adults with morbid obesity? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: bariatric surgery versus medical interventions, biliopancreatic diversion, diethylpropion, gastric bypass, gastric banding, mazindol, orlistat (alone and in combination with sibutramine), phentermine, sibutramine (alone and in combination with orlistat), sleeve gastrectomy, and vertical banded gastroplasty.
Topics: Adult; Diethylpropion; Gastric Bypass; Gastroplasty; Humans; Obesity; Obesity, Morbid; Phentermine; Weight Loss
PubMed: 21411021
DOI: No ID Found -
Journal of Clinical Medicine Feb 2022: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same... (Review)
Review
: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. : A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. : The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone ( = 5), mephedrone ( = 7), methylone ( = 1), and diethylpropion ( = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. : Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health.
PubMed: 35207278
DOI: 10.3390/jcm11041004 -
The Cochrane Database of Systematic... Oct 2019Fluoxetine is a serotonin reuptake inhibitor indicated for major depression. It is also thought to affect weight control: this seems to happen through appetite changes... (Review)
Review
BACKGROUND
Fluoxetine is a serotonin reuptake inhibitor indicated for major depression. It is also thought to affect weight control: this seems to happen through appetite changes resulting in decreased food intake and normalisation of unusual eating behaviours. However, the benefit-risk ratio of this off-label medication is unclear.
OBJECTIVES
To assess the effects of fluoxetine for overweight or obese adults.
SEARCH METHODS
We searched the Cochrane Library, MEDLINE, Embase, LILACS, the ICTRP Search Portal and ClinicalTrials.gov and World Health Organization (WHO) ICTRP Search Portal. The last date of the search was December 2018 for all databases, to which we applied no language restrictions .
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the administration of fluoxetine versus placebo, other anti-obesity agents, non-pharmacological therapy or no treatment in overweight or obese adults without depression, mental illness or abnormal eating patterns.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts and titles for relevance. Screening for inclusion, data extraction and risk of bias assessment was performed by one author and checked by the second. We assessed trials for the overall certainty of the evidence using the GRADE instrument. For additional information we contacted trial authors by email. We performed random-effects meta-analyses and calculated the risk ratio (RR) with 95% confidence intervals (95% CI) for dichotomous outcomes and the mean difference (MD) with 95% CI for continuous outcomes.
MAIN RESULTS
We identified 1036 records, scrutinized 52 full-text articles and included 19 completed RCTs (one trial is awaiting assessment). A total of 2216 participants entered the trials, 1280 participants were randomly assigned to fluoxetine (60 mg/d, 40 mg/d, 20 mg/d and 10 mg/d) and 936 participants were randomly assigned to various comparison groups (placebo; the anti-obesity agents diethylpropion, fenproporex, mazindol, sibutramine, metformin, fenfluramine, dexfenfluramine, fluvoxamine, 5-hydroxy-tryptophan; no treatment; and omega-3 gel). Within the 19 RCTs there were 56 trial arms. Fifteen trials were parallel RCTs and four were cross-over RCTs. The participants in the included trials were followed up for periods between three weeks and one year. The certainty of the evidence was low or very low: the majority of trials had a high risk of bias in one or more of the risk of bias domains.For our main comparison group - fluoxetine versus placebo - and across all fluoxetine dosages and durations of treatment, the MD was -2.7 kg (95% CI -4 to -1.4; P < 0.001; 10 trials, 956 participants; low-certainty evidence). The 95% prediction interval ranged between -7.1 kg and 1.7 kg. The MD in body mass index (BMI) reduction across all fluoxetine dosages compared with placebo was -1.1 kg/m² (95% CI -3.7 to 1.4; 3 trials, 97 participants; very low certainty evidence). Only nine placebo-controlled trials reported adverse events. A total of 399 out of 627 participants (63.6%) receiving fluoxetine compared with 352 out of 626 participants (56.2%) receiving placebo experienced an adverse event. Random-effects meta-analysis showed an increase in the risk of having at least one adverse event of any type in the fluoxetine groups compared with placebo (RR 1.18, 95% CI 0.99 to 1.42; P = 0.07; 9 trials, 1253 participants; low-certainty evidence). The 95% prediction interval ranged between 0.74 and 1.88. Following fluoxetine treatment the adverse events of dizziness, drowsiness, fatigue, insomnia and nausea were observed approximately twice as often compared to placebo. A total of 15 out of 197 participants (7.6%) receiving fluoxetine compared with 12 out of 196 participants (6.1%) receiving placebo experienced depression. The RR across all fluoxetine doses compared with placebo was 1.20 (95% CI 0.57 to 2.52; P = 0.62; 3 trials, 393 participants; very low certainty evidence). All-cause mortality, health-related quality of life and socioeconomic effects were not reported.The comparisons of fluoxetine with other anti-obesity agents (3 trials, 234 participants), omega-3 gel (1 trial, 48 participants) and no treatment (1 trial, 60 participants) showed inconclusive results (very low certainty evidence).
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that off-label fluoxetine may decrease weight compared with placebo. However, low-certainty evidence suggests an increase in the risk for dizziness, drowsiness, fatigue, insomnia and nausea following fluoxetine treatment.
PubMed: 31613390
DOI: 10.1002/14651858.CD011688.pub2 -
Current Medical Research and Opinion Jul 2013Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals... (Review)
Review
BACKGROUND
Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals who fail to achieve their intended weight goals with diet and exercise alone. Current approved therapies for weight loss include phentermine, diethylpropion, orlistat, and phentermine/topiramate. The objective of this paper was to review the place of lorcaserin, a novel serotonin 2C agonist, which was FDA approved in July 2012. Unlike contemporary lipase inhibitors and sympathomimetic amines, lorcaserin is purported to reduce food consumption and increase satiety.
SCOPE
A systematic review of the literature for all relevant articles was performed through January 2013 using MEDLINE, Web of Science, and International Pharmaceutical Abstracts using key words related to lorcaserin.
FINDINGS
Three phase III clinical studies have been published evaluating the efficacy and safety of lorcaserin in various obese populations. A higher proportion of patients receiving lorcaserin (∼47%) lost more than 5% body weight from baseline in comparison with the placebo group (∼25%; p < 0.05 in all studies). Those receiving the recommended dose of lorcaserin 10 mg twice daily lost on average ∼6 kg of body weight from baseline versus ∼3 kg with placebo. Patients with diabetes mellitus also saw significant reductions in their HbA1c with lorcaserin (∼0.9%) versus placebo (∼0.4%; p < 0.001). Lorcaserin is generally well tolerated with the most commonly experienced adverse events being nausea, dizziness, headache, upper respiratory tract infections, and nasopharyngitis. Cardiovascular evaluations showed no appreciable increase in valvulopathy with lorcaserin use versus placebo.
CONCLUSION
For now, pharmacists should continue to recommend the use of lorcaserin as a complement to, not in lieu of, ongoing lifestyle and behavioral modification.
Topics: Anti-Obesity Agents; Benzazepines; Body Weight; Eating; Humans; Obesity; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Weight Loss
PubMed: 23574263
DOI: 10.1185/03007995.2013.794776 -
Clinical Therapeutics Sep 2019Obesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A... (Meta-Analysis)
Meta-Analysis
PURPOSE
Obesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A meta-analysis was conducted to evaluate the safety and efficacy of 4 central-acting drugs, all approved in Brazil's market for weight loss.
METHODS
PubMed, EMBASE, and Cochrane library databases were searched from inception until January 2018 to retrieve randomized controlled trials comparing sibutramine, diethylpropion, mazindol, and fenproporex versus placebo in overweight or obese patients. Language was not a restriction for the database searches. We extracted and combined data from studies that reported adverse drug events and weight change. A random effects meta-analytic model was applied in all calculations. The Cochrane Collaboration tool was used to assess the quality and bias of all included studies. Quality of evidence was assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation criteria.
FINDINGS
Fifty-three studies were included, with a total of 16,903 patients with a median follow-up of 12 weeks (2-260 weeks). The appetite suppressants showed a significant weight loss compared with placebo (mean difference [MD], -4.70 kg; 95% CI, -5.25 to -4.15; I = 100%; 43 studies). There was an increased total number of adverse events, dry mouth, constipation, insomnia, dizziness, and tachycardia reported in the intervention group (risk ratio [RR], 1.06; 95% CI, 1.01 to 1.10; I = 20% [22 studies]; RR, 2.08; 95% CI, 1.76 to 2.47; I = 34% [25 studies]; RR, 2.31; 95% CI, 1.88 to 2.84; I = 0% [25 studies]; RR, 1.84; 95% CI, 1.40 to 2.39; I = 0% [17 studies]; RR, 1.78; 95% CI, 1.24 to 2.58; I = 0% [13 studies]; and RR, 2.01; 95% CI, 1.42 to 2.86; I = 0% [10 studies], respectively). Sibutramine showed a significant increase in heart rate and mean diastolic pressure compared with placebo (MD, 4.17 beats/min [95% CI, 3.60 to 4.74; I = 99%; 23 studies]; MD, 1.68 mm Hg [95% CI, 1.29 to 2.07; I = 98%; 22 studies]).
IMPLICATIONS
These drugs are effective for weight loss in overweight and obese patients; however, they increase the risk of adverse events. In fact, the evidence is of low quality, the data availability of studied agents (especially for cardiovascular outcomes) are limited, and the studies are of short duration. PROSPERO identifier: CRD42018091083.
Topics: Adult; Appetite Depressants; Central Nervous System; Humans; Overweight; Randomized Controlled Trials as Topic
PubMed: 31351676
DOI: 10.1016/j.clinthera.2019.06.005