Systematic review and meta-analysis of the efficacy and safety of amfepramone and mazindol as a monotherapy for the treatment of obese or overweight patients

Abstract

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.

Adverse Events Reported with the Use of Mazindol in Adult Obese Mexican Patients

“…Adverse events most frequently reported by Mexican patients were of gastrointestinal (dry mouth, polydipsia, constipation, thirst and nausea) or neurological (headache, dizziness, insomnia, anxiety and fatigue) origin, and relatively few cases of cardiovascular, dermatological, endocrinological or genitourinary systems. In line with our results, a meta-analysis study shows that only insomnia and constipation were associated with the consumption of Mazindol [34]. A further analysis revealed us that in patients with comorbidities, only in 9 cases of minor adverse reactions, the basic problem worsened, whereas in patients with hypertension there were not reported increments in blood pressure and, only a subject of three, who had hypoglycemia was associated with concomitant administration of hypoglycemic agents.…”

“…This profile of adverse events in Mexican patients is in line with the reported general set of adverse events and also with the statement that Mazindol is especially useful in patients with mild to moderate hypertension and diabetes mellitus [22,23]. Lucchetta et al in their meta-analysis study shows that Mazindol was not associated to major adverse reactions [34]. In fact, it has been used Mazindol in the treatment of narcolepsy and attention-deficit/hyperactivity disorder, as the incidence of central nervous stimulation is relatively low with the use of Mazindol [24,35].…”

The Appetite Suppressant D-norpseudoephedrine (Cathine) Acts via D1/D2-Like Dopamine Receptors in the Nucleus Accumbens Shell

“…Thus, NPE induces anorectic effects in the same manner as other phenethylamine derivatives such as diethylpropion, phentermine, bupropion, and cathinone; this is perhaps not surprising because chemically, these substances are all structurally related to amphetamine ( Khan et al, 2012 ). Studies in humans and in rodents revealed that amphetamine congeners produce weight loss and decreased food intake at different levels with the following strength (amphetamine > cathinone > diethylpropion ≥ phentermine > NPE > bupropion) ( Zelger and Carlini, 1980 ; Chen et al, 2001 ; Cercato et al, 2009 ; Hendricks et al, 2009 ; Kalyanasundar et al, 2015 , 2016 ; Hauner et al, 2017 ; Lucchetta et al, 2017 ; Perez et al, 2019 ). In summary, what they all have in common is that their pharmacological effects on weight loss and food intake require DA signaling ( Balcioglu and Wurtman, 1998 ; Baumann et al, 2000 ; Chen et al, 2001 ; Kalyanasundar et al, 2015 ; Lemieux et al, 2015 ).…”

Traditional Chinese medicine for restless legs syndrome

“…[ 17 ] At the same time, the potential scale reduction factor(potential scale reduction factor, PSRF) is used to evaluate the convergence of the results, When the PRSF is close to or equal to 1.00 (1.00 ≤ PSRF ≤ 1,05), it indicates that the results have good convergence and the obtained results are highly reliable. [ 18 ] At the same time, Stata software is used to calculate the SUCRA (surface under the cumulative ranking curves, SUCRA) value and the area under the SUCRA curve in order to rank the efficacy of various interventions. The value range is 0 to 100.…”