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; I2 = 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; I2 = 20% [22 studies]; RR, 2.08; 95% CI, 1.76 to 2.47; I2 = 34% [25 studies]; RR, 2.31; 95% CI, 1.88 to 2.84; I2 = 0% [25 studies]; RR, 1.84; 95% CI, 1.40 to 2.39; I2 = 0% [17 studies]; RR, 1.78; 95% CI, 1.24 to 2.58; I2 = 0% [13 studies]; and RR, 2.01; 95% CI, 1.42 to 2.86; I2 = 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; I2 = 99%; 23 studies]; MD, 1.68 mm Hg [95% CI, 1.29 to 2.07; I2 = 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.
OBJECTIVES: To review the evidence on first- and second-generation antipsychotics (FGAs and SGAs) for the treatment of various psychiatric and behavioral conditions in children, adolescents, and young adults (ages ≤ 24 years).
DATA SOURCES: Eight electronic databases, gray literature, trial registries, and reference lists.
METHODS: Two reviewers conducted study selection and risk of bias assessment independently, and resolved discrepancies by consensus. One reviewer extracted and a second verified the data. We conducted meta-analyses when appropriate and network meta-analysis across conditions for changes to body composition. We rated strength of evidence for prespecified outcomes.
RESULTS: One hundred thirty-five studies (95 trials and 40 observational studies) were included. None of the evidence was rated as high strength of evidence; results having moderate strength (i.e., probably an accurate effect) are presented (with n studies) below.SCHIZOPHRENIA AND RELATED PSYCHOSES (N = 39): Compared with placebo, SGAs as a class probably increase response rates, decrease slightly (not clinically significant for many patients) negative and positive symptoms, and improve slightly global impressions of improvement, severity, and functioning. There is likely little or no difference between high and low doses of quetiapine for clinical severity and functioning. Many outcomes for individual drug comparisons were of low or insufficient strength of evidence. BIPOLAR DISORDER (N = 19): Compared with placebo, SGAs probably decrease mania, decrease depression symptoms slightly, and improve symptom severity and global functioning to a small extent. SGAs (and aripiprazole alone) probably increase response and remission rates versus placebo for manic/mixed phases. Quetiapine likely makes little or no difference in depression. AUTISM SPECTRUM DISORDERS (N = 23): Compared with placebo, SGAs as a class probably decrease irritability, and decrease slightly lethargy/social withdrawal, stereotypy, and inappropriate speech; they likely increase response rates and (slightly) clinical severity. It is likely that aripiprazole and risperidone decrease irritability. ATTENTION DEFICIT HYPERACVTIVITY DISORDER (ADHD) AND DISRUPTIVE, IMPULSE-CONTROL, AND CONDUCT DISORDERS (N = 13): Compared with placebo, SGAs as a class (and risperidone individually) probably decrease conduct problems and aggression. Risperidone alone likely decreases hyperactivity in children with a primary diagnosis of conduct disorders or with ADHD but not responding to stimulants. OTHER CONDITIONS: All outcomes had low or insufficient strength of evidence for tic disorders (n = 12), obsessive-compulsive disorder (n = 1), depression (n = 1), eating disorders (n = 3), and behavioral issues (n = 2). HARMS ACROSS CONDITIONS: From network meta-analysis, olanzapine was more harmful for gains in weight and body mass index (BMI) than other SGAs except for clozapine and lurasidone; results were most robust for relative harm over aripiprazole, quetiapine, and risperidone, and most applicable to the short term. Findings from pairwise meta-analysis between different SGAs were similar, except for showing longer term benefit for quetiapine and risperidone versus olanzapine, and little or no short-term differences between risperidone and quetiapine, or between different doses of aripiprazole, asenapine, or quetiapine. FGAs probably cause slightly less harm for weight and BMI compared with SGAs. There is probably little or no difference in risk for somnolence between different doses of asenapine or quetiapine. There is likely little or no difference in risk for mortality or prolonged QT interval in the short term for SGAs as a class. SGAs versus placebo/no treatment probably increase short-term risk for high triglyceride levels, extrapyramidal symptoms, sedation, and somnolence.
CONCLUSION: SGAs probably improve to some extent key intermediate outcomes for which they are usually prescribed, but they have a poorer harms profile than placebo or no antipsychotic treatment, particularly for body composition and somnolence. Data for head-to-head comparisons within and between classes were generally limited and rated as insufficient or low strength of evidence. Evidence was sparse for patient-important outcomes (e.g., health-related quality of life) and outcomes for young children (<8 years). Key priorities for research are long-term comparative effectiveness and development of systems for monitoring harms.
The discovery of endocannabinoid’s role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer’s disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington’s disease, Parkinson’s disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer’s disease and dementia, Huntington’s disease, and Tourette syndrome, and dyskinesia in Parkinson’s disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Context: Various drugs affect body weight as a side effect. Objective: We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. Data Sources: MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. Study Selection: We included randomized trials that compared an a priori selected list of drugs toplacebo and measured weight change. Data Extraction:Weextracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. Results: We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin ( 2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. Conclusions: Severaldrugsareassociatedwithweightchangeofvaryingmagnitude.Dataareprovided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.
This paper reviews the literature regarding the effects of cannabinoid administration on sleep in humans. A literature search using a set of cannabinoid and sleep-related terms was conducted across eight electronic databases. Human studies that involved the administration of cannabinoids and at least one quantitative sleep-related measure were included. Review papers, opinion pieces, letters or editorials, case studies (final N < 7), published abstracts, posters, and non-English papers were excluded. Thirty-nine publications were included in the review. Findings were mixed and showed various effects of cannabinoid administration on several aspects of sleep. Methodological issues in the majority of studies to date, however, preclude any definitive conclusion.
Background: Anorexia Nervosa (AN) has a devastating impact on the psychological and physical well being of affected individuals. There is an extensive body of literature on interventions in AN, however more studies are needed to establish which form of pharmacotherapy is effective. The few meta-analyses that have been done are based on one type of medication only. This article is the first to present data on three different, most commonly used, forms of pharmacotherapy. The primary objective of this meta-analysis was to create an overview and to determine the efficacy of three forms of pharmacotherapy (antidepressants, antipsychotics, hormonal therapy) compared to treatment with placebo in patients with AN. Method: A systematic literature search was performed to identify all randomized controlled intervention trials investigating the effectiveness of pharmacotherapy for AN within the following databases: PubMed, PsycINFO, Embase and Cochrane Library. In addition, 32 relevant reviews and meta-analyses were screened for additional intervention studies. A meta-analysis was performed on a total of 18 included studies (N = 869). Efficacy was measured in terms of weight gain or weight restoration. Results: The pooled effect sizes indicating the difference between antidepressants and placebo, and between antipsychotics and placebo on weight were not significant. Because of the small sample size no meta regression and subgroup analyses could be conducted. The pooled effect size indicating the difference between hormonal therapy and the placebo condition on weight (all weight measures) at post-treatment was 0.42 (95% CI: 0.11 ~ 0.73), which was significant. For hormonal therapy heterogeneity was high (I2 = 64.70). No evidence for publication bias was found. Meta-regression analyses of the weeks of medication treatment (slope = -0.008) yielded a significant effect (p = 0.04). Conclusions: In this study we found that hormonal therapy has a significantly larger effect on weight compared to placebo in the treatment of AN. However for these analyses heterogeneity was high, which means that these results have to be regarded with caution. We found that anti-depressants and antipsychotics had no significant effect on weight compared to placebo in the treatment of AN, although the power to detect significant effects was too low.
