Risk Of Treatment-emergent Adverse Events Research Articles

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis.

To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making. A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis. Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20. For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.

Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis

What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD − 0.07, 95% CrIs − 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD − 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis.

Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis

ABSTRACT Background Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant. Methods An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms ‘Daridorexant,’ ‘RCT,’ ‘Insomnia’ trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively. Results Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one. Conclusion Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia. Prospero The registration number is CRD42022335233. Clinical trial registration www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).

Application Value of PCSK9 Inhibitor in Cardiovascular High Risk Patients: A Meta-Analysis.

Proprotein convertase subtilisin / Kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents. This drug is related to improving the prognosis of patients with cardiovascular disease (CVD). The purpose of this meta-analysis was to systematically analyze the safety and efficacy of PCSK9 inhibitors in all published randomized controlled trials (RCTs). As of October 25, 2021, we searched PubMed, EMBASE, MEDLINE, Cochrane Library and web of science. From 684 articles, we included 11 trials for meta-analysis, including 52511 participants (26938 in the PCSK9 inhibitor group and 25573 in the control group). In terms of effectiveness, PCSK9 inhibitors reduced the risk of major adverse cardiovascular events(MACE) (OR=0.89, 95% Cl: 0.83-0.95, P=0.0009), but did not significantly reduce the risk of cardiovascular death (OR=0.95, 95% Cl: 0.84-1.07, P=0.38) or all-cause death (OR=0.93, 95% Cl: 0.85-1.03, P=0.18); In terms of safety, PCSK9 did not increase the risk of treatment-emergent adverse events (TEAE)(OR=0.98, 95% Cl: 0.94-1.02, P=0.28). PCSK9 inhibitors can significantly reduce the risk of MACE in patients with high cardiovascular risk, which is well tolerated, but the impact on the risk of death is unclear.

Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials

Introduction: Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production. Methods: To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n = 7,373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm. Results: In patients randomized to vadadustat versus darbepoetin alfa, rates of TEAEs (88.9% vs. 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs. 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events. Discussion/Conclusion: Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa.

Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials.

Janus kinase (JAK) inhibitors are promising treatments for atopic dermatitis (AD). The aim of this study was to assess the efficacy and safety of JAK inhibitors for AD treatment via the “Grading of Recommendations Assessment, Development, and Evaluation” approach. We identified 15 randomized controlled trials comparing oral or topical JAK inhibitors against placebo to treat AD. A random-effects meta-analysis was performed, and the numbers-needed-to-treat (NNTs)/numbers-needed-to-harm (NNHs) were calculated. Patients treated with JAK inhibitors were associated with higher rates of achieving eczema area and severity index-75 (rate ratio (RR): 2.84; 95% confidence interval (CI): 2.20–3.67; I2: 38.9%; NNT = 3.97), Investigator’s Global Assessment response (RR: 2.99; 95% CI: 2.26–3.95; I2: 0%; NNT = 5.72), and pruritus numerical rating scale response (RR: 2.52; 95% CI: 1.90–3.35; I2: 39.4%; NNT = 4.91) than those treated with placebo. Moreover, patients treated with JAK inhibitors had a higher risk of treatment-emergent adverse events (RR: 1.14; 95% CI: 1.02–1.28; I2: 52%; NNH = 14.80) but not adverse events leading to drug discontinuation. According to the evidence-based results, JAK inhibitors are potentially effective strategies (certainty of evidence: “moderate”) for treating AD with tolerable side effects (certainty of evidence: “low”). Nevertheless, long-term follow-up is required.

Efficacy and safety of interleukin-17 inhibitors in the treatment of chronic rheumatic diseases: A combined and updated meta-analysis.

To assess the efficacy and safety of interleukin-17 inhibitors (ixekizumab, secukinumab, bimekizumab, netakimab and brodalumab) in chronic inflammatory rheumatic diseases, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A comprehensive search for randomized controlled trials (RCTs) evaluating efficacy and safety of interleukin-17 inhibitors was performed through PubMed, Embase and Cochrane Library databases. Quality assessment was performed using the Cochrane Collaboration risk of bias tool. Data were pooled using the fixed or random-effects models. Twenty RCTs were identified: of these 9 studies on patients with AS and 11 studies on patients with PsA. Concerning clinical efficacy, a pooled analysis showed interleukin-17 inhibitors had a higher response rate for the primary endpoint (p<0.05) and secondary endpoint (p<0.05) at the treatment endpoint for AS/PsA patients. Moreover, an increased risk of treatment-emergent adverse events and infection was found in AS patients (p<0.05). In contrast, no increased risk of any adverse events was reported in PsA patients. In this meta-analysis, our findings found interleukin-17 inhibitors had a significant clinical benefit in the management of AS/PsA patients.

The effect of tocilizumab on COVID-19 patient mortality: A systematic review and meta-analysis of randomized controlled trials

ObjectivesThis systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of tocilizumab for treating patients with COVID-19. MethodsThe PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform and the preprint server of medRxiv.org were searched from their inception to February 20, 2021. Only RCTs that compared the treatment efficacy and safety of tocilizumab with the placebo or the standard of care for adult patients with COVID-19 were included in this meta-analysis. The primary outcome was 28-day mortality. ResultsThis meta-analysis included eight RCTs which enrolled a total of 6314 patients for randomization, in which 3267 and 3047 patients were assigned to the tocilizumab and control groups, respectively. The mortality at day 28 was 24.4% and 29.9% in patients in the tocilizumab and control groups, respectively, meaning there was no significant difference observed between these two groups (OR, 0.92; 95% CI, 0.66–1.28; I2 = 62). This finding did not change in the subgroup analysis according to the initial use of MV or steroid while enrollment. The patients receiving tocilizumab had a lower rate of mechanical ventilation (MV) and intensive care unit (ICU) admission at day 28 compared with the control group (MV use: OR, 0.75; 95% CI, 0.62–0.90; I2 = 11; ICU admission: OR, 0.51; 95% CI, 0.28–0.92; I2 = 30). There were no significant differences between these two treatment groups in terms of the risk of treatment-emergent adverse events (AEs) (OR, 1.03; 95% CI, 0.71–1.49; I2 = 43), serious AEs (OR, 0.86; 95% CI, 0.67–1.12; I2 = 0) or infection (OR, 0.87; 95% CI, 0.63–1.20; I2 = 0). ConclusionsTocilizumab does not provide a survival benefit for patients with COVID-19, but it may help reduce the risk of MV and ICU admission. In addition, tocilizumab is a safe agent to use for the treatment of COVID-19.

Novel Tetracyclines Versus Alternative Antibiotics for Treating Acute Bacterial Infection: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis assessed the efficacy and safety of novel tetracyclines for treating acute bacterial infections. Data from PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, and Embase databases were accessed until 11 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of novel tetracyclines with that of other antibiotics for treating acute bacterial infections were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of eight RCTs were included, involving 2283 and 2197 patients who received novel tetracyclines and comparators, respectively. Overall, no significant difference was observed in the clinical response rate at test of cure between the experimental and control groups (for modified intent-to-treat [MITT] population, risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.99–1.05; for clinically evaluable [CE] population, RR: 1.02, 95% CI: 1.00–1.04; and for microbiological evaluable [ME] population, RR: 1.01, 95% CI: 0.99–1.04). No significant difference in the microbiological response at the end of treatment was observed between the experimental and control groups (for ME population, RR: 1.01, 95% CI: 0.99–1.03; for microbiological MITT population, RR: 1.01, 95% CI: 0.96–1.07). No difference was observed concerning the risk of treatment-emergent adverse events (TEAEs), serious adverse events, and discontinuation of treatment due to TEAEs and all-cause mortality between the two groups. In conclusion, clinical efficacy and safety profile for novel tetracyclines in the treatment of acute bacterial infections were found to be similar to those for other available antibiotics.

Meropenem-Vaborbactam in the Treatment of Acute Bacterial Infections.

This study reports the integrated analysis of two phase III studies of meropenem-vaborbactam in the treatment of acute bacterial infections. Targeting Antibiotic Non-Susceptible Gram-Negative Organisms (TANGO) I compared the clinical efficacy and tolerability of meropenem-vaborbactam and piperacillin-tazobactam in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). TANGO II compared the effect and safety of meropenem-vaborbactam and best-available therapy in the treatment confirmed/suspect carbapenem-resistant Enterobacteriaceae infections. The clinical cure rates at end of treatment (EOT) and test of cure (TOC) among the meropenem-vaborbactam group were non-inferior to those of the control group (at EOT, 92.5% versus 89.3%, risk ratio (RR) 1.27, 95% CI 0.64–2.50; at TOC, 86.2% versus 81.7%, RR 1.37, 95% CI 0.62–3.01). Meropenem-vaborbactam was non-inferior to comparators for microbiological eradication at EOT and TOC (at EOT, 93.3% versus 88.3%, RR 1.21, 95% CI 0.74–1.97; at TOC, 66.5% versus 59.9%, RR 1.12, 95% CI 0.97–1.30). In the subgroup of patients with cUTI/APN, meropenem-vaborbactam had similar overall success rate to the control group at EOT (RR 1.05, 95% CI 1.01–1.09) and at TOC (RR 1.05, 95% CI 0.93–1.19). Meropenem-vaborbactam had a similar risk of treatment-emergent adverse events, events leading to discontinuation of the study drug, any serious adverse events, life-threatening adverse events, drug-related adverse events, and risk of death to comparators. In conclusion, meropenem-vaborbactam was noninferior to comparators for clinical cure and microbiological eradication in the treatment of acute bacterial infection, particularly cUTI/APN, and meropenem-vaborbactam was as tolerable as comparators.

The Efficacy and Safety of Doripenem in the Treatment of Acute Bacterial Infections-A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

This study aims to assess the efficacy and safety of doripenem on treating patients with acute bacterial infections. The Pubmed, Embase, and Cochrane databases were searched up to April 2019. Only randomized clinical trials comparing doripenem and other comparators for the treatment of acute bacterial infection were included. The primary outcome was the clinical success rate and the secondary outcomes were microbiological eradication rate and risk of adverse events. Eight randomized controlled trials (RCTs) were included. Overall, doripenem had a similar clinical success rate with comparators (odds ratio [OR], 1.15; 95% CI, 0.79–1.66, I2 = 58%). Similar clinical success rates were noted between doripenem and comparators for pneumonia (OR, 0.84; 95% CI, 0.46–1.53, I2 = 72%) and for intra-abdominal infections (OR, 1.00; 95% CI, 0.57–1.72). For complicated urinary tract infection, doripenem was associated with higher success rate than comparators (OR, 1.89, 95% CI, 1.13–3.17, I2 = 0%). The pool analysis comparing doripenem and other carbapenems showed no significant differences between each other (OR, 0.96, 95% CI, 0.59–1.58, I2 = 63%). Doripenem also had a similar microbiological eradication rate with comparators (OR, 1.08; 95% CI, 0.86–1.36, I2 = 0%). Finally, doripenem had a similar risk of treatment-emergent adverse events as comparators (OR, 0.98; 95% CI, 0.83–1.17, I2 = 33%). In conclusion, the clinical efficacy of doripenem is as high as that of the comparator drugs in the treatment of acute bacterial infection; furthermore, this antibiotic is as well tolerated as the comparators.

The efficacy and safety of ceftaroline in the treatment of acute bacterial infection in pediatric patients - a systemic review and meta-analysis of randomized controlled trials.

Objectives: This meta-analysis aims to assess the clinical efficacy and safety of ceftaroline in treating acute bacterial infections – community-acquired pneumonia (CAP) and skin and skin structure infection (SSSI) in pediatric patients.Methods: The Pubmed, Embase, ClinicalTrials.gov. and the Cochrane databases were searched up to December 31, 2018. Only randomized controlled trials (RCTs) evaluating ceftaroline and other comparators in the treatment of acute bacterial infection in pediatric patients were included. The primary outcome was the clinical cure rate and the secondary outcome was the risk of adverse event.Results: Three RCTs were included. Overall, ceftaroline had a clinical cure rate at end of therapy (EOT) and test of cure (TOC) similar to comparators in the treatment of acute bacterial infection (at EOT, OR, 1.93; 95% CI, 0.88–4.25, I2=0%, and at TOC, OR, 1.36; 95% CI, 0.64–2.91, I2=14%). In addition, ceftaroline had a clinical failure rate at EOT and TOC similar to comparators in the treatment of acute bacterial infection (at EOT, OR, 0.62; 95% CI, 0.22–1.76, I2=0%, and at TOC, OR, 0.68; 95% CI, 0.24–1.91, I2=0%). No significant differences were found for the risk of treatment-emergent adverse events (TEAE) in all and different degrees between ceftaroline and comparators (OR, 0.81; 95% CI, 0.37–1.78, I2=56%). The risks of TEAE and severe adverse events related to study drug were similar between ceftaroline and comparators (TEAE related to study drug, OR, 0.98; 95% CI, 0.52–1.82, I2=0%, severe adverse event related to study drug, OR, 1.09; 95% CI, 0.22–5.44, I2=22%).Conclusions: The clinical efficacy of ceftaroline is as good as comparator therapy in the treatment of acute bacterial infections – CAP and SSSI, and this antibiotic is well tolerated as the comparators.

Assessing the burden of treatment-emergent adverse events associated with atypical antipsychotic medications

BackgroundTreatment of schizophrenia and major depressive disorder (MDD) with atypical antipsychotics (AAPs) show improved efficacy and reduced side effect burden compared with older antipsychotic medications. However, a risk of treatment-emergent adverse events (TEAEs) remains. TEAEs are hard to quantify and perspectives on the importance of TEAEs differ across patients and between patients and physicians. The current study is a qualitative assessment that investigates TEAEs of AAPs from both patient and physician perspectives to provide better understanding of the occurrence and burden of TEAEs associated with these medications.MethodsFocus groups comprised of patients with MDD and interviews with patients with schizophrenia were conducted at two qualitative research facilities, along with a physician focus group at one of the facilities. Information collected from patients included an exhaustive list of TEAEs experienced, and the frequency and level of bother of each TEAE; from psychiatrists, information included an exhaustive list of TEAEs based on personal observations and patient report, frequency of TEAEs, clinically important TEAEs, and levels of patient-perceived bother. Standard qualitative analysis methods were used to identify, quantify, characterize, and summarize patterns found in the data collected.ResultsA total of 42 patients (25 with MDD and 17 with schizophrenia) and 4 psychiatrists participated in the study. TEAEs reported as bothersome across both patients groups included cognitive issues, weight gain and/or increased appetite, low energy, extrapyramidal symptoms (EPS), and need to sleep/excessive sleep/excessive sleepiness. TEAEs considered more bothersome by patients with schizophrenia were weight gain, low energy, EPS, mental anxiety, and increased positive symptoms; those considered more bothersome by patients with MDD were cognitive issues, somnolence/sedation, and flat/restricted affect. TEAEs considered most clinically important by psychiatrists included metabolic syndrome, weight gain, neutropenia, hyperglycemia, and QT prolongation; those TEAEs considered most bothersome to patients from physicians’ perspectives included weight gain, reduced sexual desire or performance, EPS, akathisia, and hormonal issues.ConclusionsThe wide range of TEAEs that are both frequent and bothersome and the variation in perceived burden according to diagnosis highlight the need for a tailored TEAE-awareness approach when choosing an AAP.

Efficacy, tolerability, and safety of an oral enzyme combination vs diclofenac in osteoarthritis of the knee: results of an individual patient-level pooled reanalysis of data from six randomized controlled trials.

ObjectiveTo compare efficacy, safety, and tolerability of an oral enzyme combination (OEC) containing proteolytic enzymes and bioflavonoid vs diclofenac (DIC), a nonselective nonsteroidal anti-inflammatory drug in the treatment of osteoarthritis of the knee.Materials and methodsThis was an individual patient-level pooled reanalysis of patient-reported data from prospective, randomized, double-blind, parallel-group studies in adult patients with moderate-to-severe osteoarthritis of the knee treated for at least 3 weeks with OEC or DIC. Appropriate trials were identified with a systemic literature and database search. Data were extracted from the original case-report forms and reanalyzed by a blinded evaluation committee. The primary end point was the improvement of the Lequesne algofunctional index (LAFI) score at study end vs baseline. Secondary end points addressed LAFI response rates, treatment-related pain-intensity changes, adverse events, and laboratory parameters.ResultsSix trials were identified that enrolled in total 774 patients, of whom 759 had post-baseline data for safety analysis, 697 (n=348/349 with OEC/DIC) for intent to treat, 524 for per protocol efficacy analysis, and 500 for laboratory evaluation. LAFI scores – the primary efficacy end point – decreased comparably with both treatments and improved with both treatments significantly vs baseline (OEC 12.6±2.4 to 9.1±3.9, DIC 12.7±2.4 to 9.1±4.2, effect size 0.9/0.88; P<0.001 for each). In parallel, movement-related 11-point numeric rating-scale pain intensity improved significantly (P<0.001) and comparably with both treatments from baseline (6.4±1.9/6.6±1.8) to study end (3.8±2.7/3.9±2.5). Overall, 55/81 OEC/DIC patients of the safety-analysis population (14.7%/21.1%, P=0.022) reported 90/133 treatment-emergent adverse events, followed by premature treatment discontinuations in 22/39 patients (5.9%/10.2%, P=0.030). Changes in laboratory parameters were significantly less with OEC vs DIC: on average 18.8% vs 86.3% of patients presented a decrease with respect to hemoglobin, hematocrit, or erythrocyte count (P<0.001), and 28.2% vs 72.6% showed an increase in AST, ALT, or GGT (P<0.001).ConclusionWhen compared with DIC, OEC showed comparable efficacy and a superior tolerability/safety profile associated with a significantly lower risk of treatment-emergent adverse events, related study discontinuations, and changes in laboratory parameters.

The efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder: a meta-analysis of randomized controlled trials.

BackgroundVortioxetine is an investigational multimodal antidepressant. We conducted this meta-analysis to assess the efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder (MDD).MethodsRandomized controlled trials (RCTs) published in PubMed, Web of Science, Embase, and ClinicalTrials.gov were systematically reviewed to assess the treatment effects and safety profiles of patients with MDD who were treated with 10 mg vortioxetine. The outcome measures included response rate, remission rate, changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Depression (24-items) (HAM-D24), Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I) scores. Results were expressed with risk ratio or weighted mean difference with 95% confidence intervals. Pooled results were calculated using a fixed-effects model or a random-effects model according to the heterogeneity among included trials.ResultsSix RCTs with a total of 1,801 patients met the inclusion criteria and were included in this meta-analysis. The 10 mg vortioxetine dose significantly increased the response rate and remission rate in the treatment of MDD compared with placebo. Moreover, there was a statistically significant reduction from baseline in the MADRS, HAM-D24, CGI-S, and CGI-I scores with 10 mg vortioxetine vs placebo. The incidence of treatment-emergent adverse events such as nausea, vomiting, constipation, and hyperhidrosis was higher in the 10 mg vortioxetine group than in the placebo group.ConclusionVortioxetine 10 mg can significantly increase the response rate and remission rate, and reduce the MADRS, HAM-D24, CGI-S, and CGI-I scores in patients with MDD with an acceptable risk of treatment-emergent adverse events. Further well-conducted, large-scale trials are needed to validate these findings.

Alopram Efficacy In Obsessive-Compulsive Disorder Comorbid With Bipolar DisorderEscitalopram Efficacy In Obsessive-Compulsive Disorder Comorbid With Bipolar Disorder / Escitalopram Efficacy In Obsessive-Compulsive Disorder Comorbid With Bipolar Disorder

Bipolar disorder with comorbid obsessive-compulsive disorder rates vary between 7 and 39%. Inversely, 15% of OCD patients present with BPD comorbidity. Serotonin reuptake inhibitors appear to be effective pharmacological treatment for OCD. However, in the case of comorbid BPD treatment with the ones poses the risk of treatment-emergent adverse events albeit concomitant mood-stabilizing treatment. Little is known on the efficacy and safety of pharmacological intervention in BPD comorbid with OCD. No guidelines for the one exist. The paper reports on a case of a BPD patient with comorbid OCD. He was in full remission of mood disorder with severe OCD on admission. He demonstrated a functional improvement of OCD symptoms in response to the addition of escitalopram (40mg) to divalproex along with behavioral intervention. The case demonstrates efficacy and safety along with a good tolerance of the combination of divalproex and high doses of escitalopram in an OCD patient in course of the BPD.

A review of the use of frovatriptan in the treatment of menstrually related migraine

Menstrual migraine (MM) is a highly prevalent condition associated with considerable disability. Migraine attacks occur exclusively around the menstrual period in approximately 10% of women with migraine, that is, pure menstrual migraine, while at least 50% of them also experience migraine at other times of the month, that is, menstrually related migraine (MRM). The therapeutic approach to patients with MRM is based on treatment of the attack, or prophylactic strategies. Triptans are recommended as first-line treatments for moderate to severe migraine attacks, including MM. Frovatriptan is one of the newest triptans. Its high affinity for 5-HT1B/1D receptors and long half-life contribute to its distinctive clinical effect, characterized by a more sustained and prolonged effect than other triptans. Indeed, frovatriptan proved to be effective in treating the acute attack, but was particularly effective in the short-term preventive therapy of MM. In addition, frovatriptan is one of the safest triptans, with the lowest risk of treatment-emergent adverse events. Following extensive evidence from randomized pharmacological trials, frovatriptan has now gained a grade A recommendation from the guidelines for short-term prophylaxis of MM. Recent post-hoc analyses of direct comparative trials also suggest that frovatriptan might have an important role in the acute treatment of MRM. In these studies, frovatriptan showed pain relief and pain-free rates similar to those of zolmitriptan, rizatriptan, and almotriptan, but with significantly lower recurrence rates. More well-designed, randomized, prospective studies, specifically enrolling women with MM, will be needed in the near future to confirm the efficacy of frovatriptan in this migraine subtype.