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Expert Review of Neurotherapeutics 2016Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard... (Review)
Review
Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.
Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 26693882
DOI: 10.1586/14737175.2016.1135735 -
Systematic Reviews Mar 2023Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities... (Review)
Review
BACKGROUND
Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available.
OBJECTIVE
The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020.
METHODS
A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020.
RESULTS
A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence.
CONCLUSIONS
This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.
Topics: Humans; Prospective Studies; Keloid; Fluorouracil; Adrenal Cortex Hormones; Verapamil; Treatment Outcome
PubMed: 36918908
DOI: 10.1186/s13643-023-02192-7 -
The Cochrane Database of Systematic... Sep 2022Hypertrophic and keloid scars are common skin conditions resulting from abnormal wound healing. They can cause itching, pain and have a negative physical and... (Review)
Review
BACKGROUND
Hypertrophic and keloid scars are common skin conditions resulting from abnormal wound healing. They can cause itching, pain and have a negative physical and psychological impact on patients' lives. Different approaches are used aiming to improve these scars, including intralesional corticosteroids, surgery and more recently, laser therapy. Since laser therapy is expensive and may have adverse effects, it is critical to evaluate the potential benefits and harms of this therapy for treating hypertrophic and keloid scars.
OBJECTIVES
To assess the effects of laser therapy for treating hypertrophic and keloid scars.
SEARCH METHODS
In March 2021 we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL EBSCO Plus and LILACS. To identify additional studies, we also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports. There were no restrictions with respect to language, date of publication, or study setting.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) for treating hypertrophic or keloid scars (or both), comparing laser therapy with placebo, no intervention or another intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted the data, assessed the risk of bias of included studies and carried out GRADE assessments to assess the certainty of evidence. A third review author arbitrated if there were disagreements.
MAIN RESULTS
We included 15 RCTs, involving 604 participants (children and adults) with study sample sizes ranging from 10 to 120 participants (mean 40.27). Where studies randomised different parts of the same scar, each scar segment was the unit of analysis (906 scar segments). The length of participant follow-up varied from 12 weeks to 12 months. All included trials had a high risk of bias for at least one domain: all studies were deemed at high risk of bias due to lack of blinding of participants and personnel. The variability of intervention types, controls, follow-up periods and limitations with report data meant we pooled data for one comparison (and only two outcomes within this). Several review secondary outcomes - cosmesis, tolerance, preference for different modes of treatment, adherence, and change in quality of life - were not reported in any of the included studies. Laser versus no treatment: We found low-certainty evidence suggesting there may be more hypertrophic and keloid scar improvement (that is scars are less severe) in 585-nm pulsed-dye laser (PDL) -treated scars compared with no treatment (risk ratio (RR) 1.96; 95% confidence interval (CI): 1.11 to 3.45; two studies, 60 scar segments). It is unclear whether non-ablative fractional laser (NAFL) impacts on hypertrophic scar severity when compared with no treatment (very low-certainty evidence). It is unclear whether fractional carbon dioxide (CO) laser impacts on hypertrophic and keloid scar severity compared with no treatment (very low-certainty evidence). Eight studies reported treatment-related adverse effects but did not provide enough data for further analyses. Laser versus other treatments: We are uncertain whether treatment with 585-nm PDL impacts on hypertrophic and keloid scar severity compared with intralesional corticosteroid triamcinolone acetonide (TAC), intralesional Fluorouracil (5-FU) or combined use of TAC plus 5-FU (very low-certainty evidence). It is also uncertain whether erbium laser impacts on hypertrophic scar severity when compared with TAC (very low-certainty evidence). Other comparisons included 585-nm PDL versus silicone gel sheeting, fractional CO laser versus TAC and fractional CO laser versus verapamil. However, the authors did not report enough data regarding the severity of scars to compare the interventions. As only very low-certainty evidence is available on treatment-related adverse effects, including pain, charring (skin burning so that the surface becomes blackened), telangiectasia (a condition in which tiny blood vessels cause thread-like red lines on the skin), skin atrophy (skin thinning), purpuric discolorations, hypopigmentation (skin colour becomes lighter), and erosion (loss of part of the top layer of skin, leaving a denuded surface) secondary to blistering, we are not able to draw conclusions as to how these treatments compare. Laser plus other treatment versus other treatment: It is unclear whether 585-nm PDL plus TAC plus 5-FU leads to a higher percentage of good to excellent improvement in hypertrophic and keloid scar severity compared with TAC plus 5-FU, as the certainty of evidence has been assessed as very low. Due to very low-certainty evidence, it is also uncertain whether CO laser plus TAC impacts on keloid scar severity compared with cryosurgery plus TAC. The evidence is also very uncertain about the effect of neodymium-doped yttrium aluminium garnet (Nd:YAG) laser plus intralesional corticosteroid diprospan plus 5-FU on scar severity compared with diprospan plus 5-FU and about the effect of helium-neon (He-Ne) laser plus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream on scar severity compared with decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream. Only very low-certainty evidence is available on treatment-related adverse effects, including pain, atrophy, erythema, telangiectasia, hypopigmentation, regrowth, hyperpigmentation (skin colour becomes darker), and depigmentation (loss of colour from the skin). Therefore, we are not able to draw conclusions as to how these treatments compare. AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the effectiveness of laser therapy for treating hypertrophic and keloid scars. The available information is also insufficient to perform a more accurate analysis on treatment-related adverse effects related to laser therapy. Due to the heterogeneity of the studies, conflicting results, study design issues and small sample sizes, further high-quality trials, with validated scales and core outcome sets should be developed. These trials should take into consideration the consumers' opinion and values, the need for long-term follow-up and the necessity of reporting the rate of recurrence of scars to determine whether lasers may achieve superior results when compared with other therapies for treating hypertrophic and keloid scars.
Topics: Adrenal Cortex Hormones; Adult; Aluminum; Atrophy; Carbon Dioxide; Child; Cicatrix, Hypertrophic; Dimethylpolysiloxanes; Erbium; Fluorouracil; Helium; Humans; Hypertrophy; Hypopigmentation; Keloid; Laser Therapy; Neodymium; Neon; Pain; Silicone Gels; Telangiectasis; Triamcinolone Acetonide; Verapamil; Wound Healing; Yttrium
PubMed: 36161591
DOI: 10.1002/14651858.CD011642.pub2 -
The Cochrane Database of Systematic... Jun 2014Bronchiolitis is an acute, viral lower respiratory tract infection affecting infants and is sometimes treated with bronchodilators. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is an acute, viral lower respiratory tract infection affecting infants and is sometimes treated with bronchodilators.
OBJECTIVES
To assess the effects of bronchodilators on clinical outcomes in infants (0 to 12 months) with acute bronchiolitis.
SEARCH METHODS
We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January Week 2, 2014) and EMBASE (1998 to January 2014).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing bronchodilators (other than epinephrine) with placebo for bronchiolitis.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data. We obtained unpublished data from trial authors.
MAIN RESULTS
We included 30 trials (35 data sets) representing 1992 infants with bronchiolitis. In 11 inpatient and 10 outpatient studies, oxygen saturation did not improve with bronchodilators (mean difference (MD) -0.43, 95% confidence interval (CI) -0.92 to 0.06, n = 1242). Outpatient bronchodilator treatment did not reduce the rate of hospitalization (11.9% in bronchodilator group versus 15.9% in placebo group, odds ratio (OR) 0.75, 95% CI 0.46 to 1.21, n = 710). Inpatient bronchodilator treatment did not reduce the duration of hospitalization (MD 0.06, 95% CI -0.27 to 0.39, n = 349).Effect estimates for inpatients (MD -0.62, 95% CI -1.40 to 0.16) were slightly larger than for outpatients (MD -0.25, 95% CI -0.61 to 0.11) for oximetry. Oximetry outcomes showed significant heterogeneity (I(2) statistic = 81%). Including only studies with low risk of bias had little impact on the overall effect size of oximetry (MD -0.38, 95% CI -0.75 to 0.00) but results were close to statistical significance.In eight inpatient studies, there was no change in average clinical score (standardized MD (SMD) -0.14, 95% CI -0.41 to 0.12) with bronchodilators. In nine outpatient studies, the average clinical score decreased slightly with bronchodilators (SMD -0.42, 95% CI -0.79 to -0.06), a statistically significant finding of questionable clinical importance. The clinical score outcome showed significant heterogeneity (I(2) statistic = 73%). Including only studies with low risk of bias reduced the heterogeneity but had little impact on the overall effect size of average clinical score (SMD -0.22, 95% CI -0.41 to -0.03).Sub-analyses limited to nebulized albuterol or salbutamol among outpatients (nine studies) showed no effect on oxygen saturation (MD -0.19, 95% CI -0.59 to 0.21, n = 572), average clinical score (SMD -0.36, 95% CI -0.83 to 0.11, n = 532) or hospital admission after treatment (OR 0.77, 95% CI 0.44 to 1.33, n = 404).Adverse effects included tachycardia, oxygen desaturation and tremors.
AUTHORS' CONCLUSIONS
Bronchodilators such as albuterol or salbutamol do not improve oxygen saturation, do not reduce hospital admission after outpatient treatment, do not shorten the duration of hospitalization and do not reduce the time to resolution of illness at home. Given the adverse side effects and the expense associated with these treatments, bronchodilators are not effective in the routine management of bronchiolitis. This meta-analysis continues to be limited by the small sample sizes and the lack of standardized study design and validated outcomes across the studies. Future trials with large sample sizes, standardized methodology across clinical sites and consistent assessment methods are needed to answer completely the question of efficacy.
Topics: Acute Disease; Albuterol; Ambulatory Care; Bronchiolitis; Bronchodilator Agents; Hospitalization; Humans; Infant; Infant, Newborn; Oxygen; Randomized Controlled Trials as Topic
PubMed: 24937099
DOI: 10.1002/14651858.CD001266.pub4 -
Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
Journal of Clinical Pharmacology Apr 2022This article discusses current literature on the use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in the treatment of posttraumatic stress disorder... (Meta-Analysis)
Meta-Analysis Review
This article discusses current literature on the use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD). MDMA, the intended active ingredient in illicit Ecstasy or Molly products, is a psychedelic that causes an elevated mood, feeling of bonding, and increased energy. In MDMA-assisted psychotherapy, patients are subjected to 2 or 3 multihour sessions of therapy with a team of psychiatrists. The dosing of MDMA is used to allow the therapist to probe the underlying trauma without causing emotional distress. The use of MDMA-assisted psychotherapy treatment reduced patient's Clinician-Administered PTSD Scale (CAPS) scores from baseline more than control psychotherapy (-22.03; 95%CI, -38.53 to -5.52) but with high statistical heterogeneity. MDMA-assisted psychotherapy enhanced the achievement of clinically significant reductions in CAPS scores (relative risk, 3.65; 95%CI, 2.39-5.57) and CAPS score reductions sufficient to no longer meet the definition of PTSD (relative risk, 2.10; 95%CI, 1.37-3.21) with no detected statistical heterogeneity. While therapy was generally safe and well tolerated, bruxism, anxiety, jitteriness, headache, and nausea are commonly reported. While MDMA-assisted psychotherapy has been shown to be an effective therapy for patients with PTSD with a reasonable safety profile, use of unregulated MDMA or use in the absence of a strongly controlled psychotherapeutic environment has considerable risks.
Topics: Combined Modality Therapy; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 34708874
DOI: 10.1002/jcph.1995 -
Psychopharmacology Aug 2020Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders. (Meta-Analysis)
Meta-Analysis
RATIONALE
Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders.
OBJECTIVES
We conducted a systematic review and meta-analysis to evaluate usefulness of an agonist approach as treatment of (psycho)stimulant use disorder (PSUD).
METHODS
We reviewed PubMed/Medline, LILACS, and ClinicalTrials.gov databases searching for randomized, double-blind, placebo-controlled, parallel-design studies evaluating outcomes of individuals treated for cocaine- or amphetamine-type substance use disorder. We combined results of all trials that included the following prescription psychostimulants (PPs): modafinil, methylphenidate, or amphetamines (mixed amphetamine salts, lisdexamphetamine, and dextroamphetamine). The combined sample consisted of 2889 patients. Outcomes of interest included the following: drug abstinence (defined as 2-3 weeks of sustained abstinence and the average maximum days of consecutive abstinence), percentage of drug-negative urine tests across trial, and retention in treatment. We conducted random-effects meta-analyses and assessed quality of evidence using the GRADE system.
RESULTS
Thirty-eight trials were included. Treatment with PPs increases rates of sustained abstinence [risk ratio (RR) = 1.45, 95% confidence interval (CI) = (1.10, 1.92)] and duration of abstinence [mean difference (MD) = 3.34, 95% CI = (1.06, 5.62)] in patients with PSUD, particularly those with cocaine use disorder (very low-quality evidence). Prescription amphetamines were particularly efficacious in promoting sustained abstinence in patients with cocaine use disorder [RR = 2.44, 95% CI = (1.66, 3.58)], and higher doses of PPs were particularly efficacious for treatment of cocaine use disorder [RR = 1.95, 95% CI = (1.38, 2.77)] (moderate-quality evidence). Treatment with prescription amphetamines also yielded more cocaine-negative urines [MD = 8.37%, 95% CI = (3.75, 12.98)]. There was no effect of PPs on the retention in treatment.
CONCLUSION
Prescription psychostimulants, particularly prescription amphetamines given in robust doses, have a clinically significant beneficial effect to promote abstinence in the treatment of individuals with PSUD, specifically the population with cocaine use disorder.
Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Prescription Drugs; Randomized Controlled Trials as Topic; Substance-Related Disorders; Treatment Outcome
PubMed: 32601988
DOI: 10.1007/s00213-020-05563-3 -
Diabetes, Obesity & Metabolism Sep 2023To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. (Meta-Analysis)
Meta-Analysis
AIM
To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight.
MATERIALS AND METHODS
We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied.
RESULTS
A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], -9.02 kg [95% CI: -10.42, -7.63]; moderate certainty) and phentermine/topiramate (MD, -8.10 kg [95% CI: -10.14, -6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, -7.84 cm [95% CI: -9.34, -6.34]; moderate certainty) and phentermine/topiramate (MD, -6.20 cm [95% CI: -7.46, -4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants).
CONCLUSIONS
Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.
Topics: Adult; Humans; Overweight; Topiramate; Network Meta-Analysis; Randomized Controlled Trials as Topic; Obesity; Phentermine
PubMed: 37254688
DOI: 10.1111/dom.15138 -
The Lancet. Psychiatry Mar 2024There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression.
METHODS
In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926.
FINDINGS
Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes.
INTERPRETATION
According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies.
FUNDING
None.
Topics: Male; Female; Humans; Middle Aged; Depressive Disorder, Major; Fluoxetine; Perphenazine; Network Meta-Analysis; Bipolar Disorder; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Depression; Antipsychotic Agents; Olanzapine
PubMed: 38360024
DOI: 10.1016/S2215-0366(24)00006-3