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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 -
The Cochrane Database of Systematic... Sep 2016Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be... (Review)
Review
BACKGROUND
Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment.
OBJECTIVES
To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy.
SEARCH METHODS
This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field.
SELECTION CRITERIA
We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants and placebo (RD 0.00, 95% CI -0.01 to 0.01; RD 0.00, 95% CI -0.02 to 0.01, respectively). When we included the type of drug as a moderating variable, the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dexamphetamine than with placebo. Psychostimulants also appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone-maintained, dual heroin-cocaine addicts. Retention to treatment was low, though, so our results may be compromised by attrition bias. We found no evidence of publication bias.
AUTHORS' CONCLUSIONS
This review found mixed results. Psychostimulants improved cocaine abstinence compared to placebo in some analyses but did not improve treatment retention. Since treatment dropout was high, we cannot rule out the possibility that these results were influenced by attrition bias. Existing evidence does not clearly demonstrate the efficacy of any pharmacological treatment for cocaine dependence, but substitution treatment with psychostimulants appears promising and deserves further investigation.
PubMed: 27670244
DOI: 10.1002/14651858.CD007380.pub4 -
European Journal of Pediatrics Jan 2016Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances... (Review)
Review
UNLABELLED
Prader-Willi syndrome (PWS) is a rare genetic syndrome. The phenotype includes moderate to intellectual disability, dysmorphia, obesity, and behavioral disturbances (e.g., hetero and self-injurious behaviors, hyperphagia, psychosis). Psychotropic medications are widely prescribed in PWS for symptomatic control. We conducted a systematic review of published literature to examine psychotropic medications used in PWS. MEDLINE was searched to identify articles published between January 1967 and December 2014 using key words related to pharmacological treatments and PWS. Articles with original data were included based on a standardized four-step selection process. The identification of studies led to 241 records. All selected articles were evaluated for case descriptions (PWS and behavioral signs) and treatment (type, titration, efficiency, and side effects). Overall, 102 patients were included in these studies. Treatment involved risperidone (three reports, n = 11 patients), fluoxetine (five/n = 6), naltrexone (two/n = 2), topiramate (two/n = 16), fluvoxamine (one/n = 1), mazindol (one/n = 2), N-acetyl cysteine (one/n = 35), rimonabant (one/n = 15), and fenfluramine (one/n = 15).
CONCLUSION
We identified promising treatment effects with topiramate for self-injury and impulsive/aggressive behaviors, risperidone for psychotic symptoms associated with uniparental disomy (UPD), and N-acetyl cysteine for skin picking. The pharmacological approach of behavioral impairment in PWS has been poorly investigated to date. Further randomized controlled studies are warranted.
WHAT IS KNOWN
Behavioral disturbances in Prader-Willi syndrome including aggressive reactions, skin picking, and hyperphagia might be very difficult to manage. Antipsychotic drugs are widely prescribed, but weight gain and increased appetite are their major side effects.
WHAT IS NEW
Topiramate might be efficient for self-injury and impulsive/aggressive behaviors, N-acetyl cysteine is apromising treatment for skin picking and Antidepressants are indicated for OCD symptoms. Risperidone is indicated in case of psychotic symptoms mainly associated with uniparental disomy.
Topics: Adolescent; Child; Child, Preschool; Cystine; Fructose; Humans; Prader-Willi Syndrome; Psychotropic Drugs; Risperidone; Topiramate
PubMed: 26584571
DOI: 10.1007/s00431-015-2670-x -
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 -
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 -
Current Diabetes Reviews 2020Obesity shows a multifactorial disease and presents a serious public health problem, with an alarming epidemic character. According to NHANES (National Health and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Obesity shows a multifactorial disease and presents a serious public health problem, with an alarming epidemic character. According to NHANES (National Health and Nutrition Examination Survey) from 2015 to 2016, 39.6% of American adults and 18.5% of young people were obese and 7.7% of adults and 5.6% of young people had severe obesity. Brazil ranks fifth in the world ranking, with about 18 million people reaching up to 70 million overweight individuals. Despite shortterm weight loss with diet and exercise, weight regain continues to be a concern. Anti-obesity drugs, such as Sibutramine (SIB), Phentermine (PHEN), Fenproporex (FEN), Mazindol (MAZ), Amfepramone (AMFE) and Orlistat (ORL) may play a role in weight reduction in patients whose condition is refractory to non- and maintenance of weight loss.
OBJECTIVE
A systematic review followed by meta-analysis of randomized clinical trials over the past five years to explore the efficacy and safety of anorexigenic drugs for weight reduction and consequent treatment of obesity.
METHODS
The search strategy in MEDLINE / Pubmed, Web of Science, ScienceDirect Journals (Elsevier), Scopus (Elsevier), OneFile (Gale) is as follows : - search for mesh terms (Sibutramine, Phentermine, Fenproporex, Mazindol, Amfepramone , Orlistat, Weight loss, Safety), and the use of booleans "and" between mesh terms and "or" among historical findings.
RESULTS
It was observed that in the last five years of randomized studies no significant general complications were found, with only 5.7%. The mean overall weight loss was 6.18 (± 2.8) kg in the mean time of 12 months. The overall success rate among these drugs was 80.18%. The p-value values did not present a significant statistical difference, being p <0.05 within each drug group analyzed, for both weight and success rates.
CONCLUSION
The scientific findings of randomized studies on the use of anorexigenic drugs to treat obesity have shown safety and efficiency in the last five years, with a reasonable weight loss and no significant complications.
Topics: Appetite Depressants; Humans; Obesity; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 31729302
DOI: 10.2174/1573399815666191113125247 -
Clinics (Sao Paulo, Brazil) Mar 2018[This corrects the article doi: 10.6061/clinics/2017(05)10].
[This corrects the article doi: 10.6061/clinics/2017(05)10].
PubMed: 29561929
DOI: 10.6061/clinics/2018/e1err -
Drug and Alcohol Dependence Nov 2020Stimulant (cocaine and/or methamphetamine) use has increased among people with opioid use disorder. We conducted a systematic review of medications for stimulant use... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant (cocaine and/or methamphetamine) use has increased among people with opioid use disorder. We conducted a systematic review of medications for stimulant use disorders in this population.
METHODS
We searched for randomized controlled trials in multiple databases through April 2019, and dual-screened studies using pre-specified inclusion criteria. Primary outcomes were abstinence defined as stimulant-negative urine screens for ≥3 consecutive weeks; overall use as the proportion of stimulant-negative urine specimens; and retention as the proportion of participants who completed treatment. We rated strength of evidence using established criteria and conducted meta-analyses of comparable interventions and outcomes.
RESULTS
Thirty-four trials of 22 medications focused on cocaine use disorder in patients with opioid use disorder. Most studies enrolled participants stabilized on opioid maintenence therapy, generally methadone. None of the six studies that assessed abstinence found significant differences between groups. We found moderate-strength evidence that antidepressants (desipramine, bupropion, and fluoxetine) worsened retention. There was moderate-strength evidence that disulfiram worsened treatment retention (N = 605, RR 0.86, 95 % CI 0.77 to 0.95). We found low-strength evidence that psychostimulants (mazindol and dexamphetamine) may reduce cocaine use, though the difference was not statistically significant (standard mean difference 0.35 [95 % CI -0.05 to 0.74]). There was only 1 trial for methamphetamine use disorder, which showed insufficient-strength evidence for naltrexone.
CONCLUSIONS
Co-occurring stimulant/opioid use disorder is an important problem for targeting future research. Medication trials for methamphetamine use disorder are lacking in this population. Most of the medications studied for cocaine use were ineffective, although psychostimulants warrant further study.
Topics: Analgesics, Opioid; Antidepressive Agents; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Female; Humans; Methadone; Naltrexone; Opioid-Related Disorders
PubMed: 32861136
DOI: 10.1016/j.drugalcdep.2020.108193 -
Expert Review of Neurotherapeutics Jul 2019: Despite stimulants being highly efficacious in short-term randomized controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of...
: Despite stimulants being highly efficacious in short-term randomized controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of novel non-stimulant options are currently in the pipeline for the treatment of attention-deficit/hyperactivity disorder (ADHD). : The authors conducted a systematic review of RCTs registered in ClinicalTrials.gov in the past 5 years (January 2014 and February 2019), supplemented by searches in PubMed, Web of Science, and drug manufacturer websites to find recent RCTs on novel non-stimulant ADHD medications. : The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), , and Molindone hydrochloride (SPN-810). Given the high effect size found in RCTs of stimulants in terms of efficacy on ADHD core symptoms, it is unlikely that these novel agents will show better efficacy than stimulants, at the group level. However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a 'one size fits all' to a 'precision medicine' approach.
Topics: Attention Deficit Disorder with Hyperactivity; Cannabinoid Receptor Modulators; Central Nervous System Stimulants; Humans; Neurotransmitter Agents; Piperidines; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 31167583
DOI: 10.1080/14737175.2019.1628640