Selegiline 5mg/5ml oral solution

IntroductionAtypical depression is a highly prevalent subtype that includes mood reactivity, hypersomnia, and leaden paralysis, necessitating different therapeutic approaches than melancholic depression. No network meta-analysis has been conducted on pharmacological treatments for atypical depression.MethodsWe performed a PRISMA-compliant systematic review and network meta-analysis searching PubMed/Central, Clinicaltrials.gov, Embase, PsycINFO, Scopus, WebOfScience for randomized controlled trials (RCTs) testing pharmacological interventions for atypical depression until 04/24/24 (PROSPERO: CRD42024540262). Depressive symptom change (standardized mean difference/SMD), response, and all-cause discontinuation (acceptability) (risk ratio/RR) were co-primary outcomes; tolerability was the secondary outcome. Risk-of-bias and global/local inconsistencies were measured, and Confidence in Network Meta-Analysis (CINeMA) was used to assess the confidence in the evidence.ResultsOut of 2214 hits, we included 21 eligible RCTs, 20 entering the NMA. For efficacy (k = 16, N = 903, treatments=12), only phenelzine outperformed placebo (SMD=-1.31, 95 %C.I.=[-2.14;-0.49]). Phenelzine, moclobemide, isocarboxazid, imipramine, selegiline, sertraline, and fluoxetine all outperformed nortriptyline (from SMD=-4.54, 95 %C.I.=[-8.02;-1.07] to SMD=-3.08, 95 %C.I.=[-5.42; -0.75]). Regarding response (k = 13, N = 1442, treatments=7), phenelzine (RR=2.58, 95 %C.I.=[2.02-3.31]), sertraline (RR=2.25, 95 %C.I.=[1.01-4.99]), moclobemide (RR=2.16, 95 %C.I.=[1.12-4.19]), fluoxetine (RR=1.89, 95 %C.I.=[1.30-2.76]) and imipramine (RR=1.76, 95 %C.I.=[1.35-2.28]) outperformed placebo, and phenelzine also outperformed imipramine (RR=1.56, 95 %C.I.=[1.25-1.96]). No treatment was significantly different from placebo for acceptability. No intervention outperformed placebo on any outcome in sensitivity analyses upon exclusion of high-risk-of-bias and intention-to-treat trials, likely due to a loss in power of the analysis, and overall CINeMA ratings were low/very low.ConclusionsPhenelzine might perform better than other compounds, but several drugs outperformed placebo in response. Nortriptyline performed worse than other treatments. High-quality studies are needed.

Abstract licence: CC BY-NC-ND

Background and objectivesQuality of life (QoL) is a critical outcome in the management of Parkinson's disease (PD), and is often affected more by non-motor symptoms (NMS) than motor features. While monoamine oxidase-B (MAO-B) and catechol-O-methyltransferase (COMT) inhibitors are commonly used with levodopa, their comparative impacts on QoL remains unclear. This study aimed to compare the effects of MAO-B and COMT inhibitors on global and domain-specific QoL in patients with PD using a Bayesian network meta-analysis (NMA).MethodsA comprehensive literature search was conducted using PubMed/Medline, Cochrane Library and Embase databases from the inception through April 30, 2025. Randomized controlled trials evaluating QoL using PDQ-39 or PDQ-8 in patients treated with MAO-B inhibitors (rasagiline, selegiline, safinamide) or COMT inhibitors (entacapone, opicapone, tolcapone) were included. A Bayesian NMA was performed using the "gemtc" package in R. Treatment effects were expressed as standardized mean differences (SMDs) with 95% credible intervals (CrIs). Treatment ranking was estimated using surface under the cumulative ranking curve (SUCRA) values.ResultsSixteen RCTs comprised of 3,802 patients were included. The combination of extended-release rasagiline and pramipexole (P2B001) showed the most significant improvement in global QoL (SMD = -4.16; 95% CrI: -7.24 to -1.05), followed by rasagiline monotherapy (SMD = -2.38; 95% CrI: -4.32 to -0.42). Safinamide 100 mg significantly improved emotional well-being (SMD = -2.56; 95% CrI: -5.13 to -0.04). SUCRA rankings confirmed the superior probability of benefits for rasagiline-based interventions across multiple QoL dimensions.ConclusionThis network meta-analysis provides evidence that MAO-B inhibitors, particularly rasagiline and safinamide, may offer broader QoL benefits in patients with PD, especially in NMS such as emotional well-being. These findings support a more symptom-oriented and individualized treatment approach should be provided to patients with PD. Further well-designed head-to-head studies using standardized QoL measures and extended follow-up are needed to confirm these findings and guide clinical practice.Systematic review registrationRegistered in PROSPERO (CRD420251013028): https://www.crd.york.ac.uk/PROSPERO/view/CRD420251013028.

Abstract licence: CC BY