CNS Drugs

Ahmed, Sherihan Rezk; Nahas, Nevine El; Khalil, Mohamed Fouad Elsayed; Elbassiouny, Ahmed; Almoataz, Mohamed Ahmed; Omar, Tarek Youssif; Daabis, Ahmed Mohamed Ali; Refat, Hossam Mohamed; Ebied, Ahmed Ahmed Mohamed Kamal; Hassan, Asmaa Mohammed; Mohamed, Diaa Mostafa Atiaa; Ismaiel, Mohamed; Zeinhom, Mohamed G.

2024 CNS Drugs

doi: 10.1007/s40263-024-01127-7pmid: 39520630

BackgroundMany studies evaluated the efficacy and safety of ticagrelor versus clopidogrel in patients with ischemic stroke; none of these trials included North African participants, and all of these trials comprised only participants who experienced transient ischemic attack (TIA) or minor stroke.ObjectivesWe compared the efficacy and safety of ticagrelor versus clopidogrel in patients with first-ever noncardioembolic moderate or moderate-to-severe ischemic stroke.MethodsOur trial involved 900 first-ever noncardioembolic patients with acute ischemic stroke (AIS) who randomly received either loading and maintenance doses of ticagrelor or clopidogrel within the first 24 h of stroke onset.ResultsWe involved 900 patients in the intention-to-treat analysis. A total of 39 (8.7%) patients in ticagrelor arm and 62 (13.8%) in clopidogrel arm experienced a new stroke [hazard ratio (HR) 0.46; 95% confidence interval (CI) 0.34–0.83; P value = 0.006]. A total of 57 (12.7%) patients in ticagrelor group and 80 (17.8%) patients in clopidogrel group experienced composite of new stroke, myocardial infarction (MI), or death due to vascular insults (HR 0.51; 95% CI 0.43–0.82; P value = 0.004). Participants who received ticagrelor experienced less frequent unfavorable outcomes. We found no significant variation between our study's two arms concerning the hemorrhagic and non-hemorrhagic complications.ConclusionPatients with noncardioembolic moderate or moderate-to-severe ischemic stroke who received ticagrelor within the first 24 h after ischemic stroke had better clinical outcomes based on recurrent stroke rates and unfavorable modified Rankin Scale (mRS) rates compared with those who received clopidogrel. There were no significant variations between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications.RegistrationClinicalTrials.gov identifier number NCT05553613.

De Angelis, Floriana; Nistri, Riccardo; Wright, Sarah

2024 CNS Drugs

doi: 10.1007/s40263-024-01132-wpmid: 39581949

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterised by inflammation, demyelination and neurodegeneration. Although several drugs are approved for MS, their efficacy in progressive disease is modest. Addressing disease progression as a treatment goal in MS is challenging due to several factors. These include a lack of complete understanding of the pathophysiological mechanisms driving MS and the absence of sensitive markers of disease progression in the short-term of clinical trials. MS usually begins at a young age and lasts for decades, whereas clinical research often spans only 1–3 years. Additionally, there is no unifying definition of disease progression. Several drugs are currently being investigated for progressive MS. In addition to new medications, the rise of new technologies and of adaptive trial designs is enabling larger and more integrated data collection. Remote assessments and decentralised clinical trials are becoming feasible. These will allow more efficient and large studies at a lower cost and with less burden on study participants. As new drugs are developed and research evolves, we anticipate a concurrent change in patient care at various levels in the foreseeable future. We conducted a narrative review to discuss the challenges of accurately measuring disease progression in contemporary MS drug trials, some new research trends and their implications for patient care.

Miwa, Toru

2024 CNS Drugs

doi: 10.1007/s40263-024-01135-7pmid: 39576425

Zhou, Xin; Zhang, Aiping; Lin, Riyang

2024 CNS Drugs

doi: 10.1007/s40263-024-01134-8pmid: 39576426

Correll, Christoph U.; Kim, Edward; Sliwa, Jennifer Kern; Hamm, Wayne; Gopal, Srihari; Mathews, Maju; Venkatasubramanian, Raja; Saklad, Stephen R.

2024 CNS Drugs

doi: 10.1007/s40263-024-01138-4pmid: 39589630

Wang, Enhui; Liu, Yilin; Wang, Yucheng; Han, Xinyu; Zhou, Yifang; Zhang, Lingli; Tang, Yanqing

2024 CNS Drugs

doi: 10.1007/s40263-024-01131-xpmid: 39528870

BackgroundA network meta-analysis was performed to evaluate the risk of congenital malformations and other prenatal outcomes in fetuses after exposure to antipsychotic medications and mood stabilizers during pregnancy.MethodsWe searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to 15 December 2023, to identify experimental and observational studies comparing antipsychotic and mood stabilizer treatments with control treatments (no exposure). The primary outcome of the study was the incidence of congenital malformations and the secondary outcomes were preterm birth and spontaneous abortion. Additionally, two authors independently assessed the risk of bias in each domain of the included studies using the ROBINS-I tool and evaluated the quality of evidence using the CINeMA rating tool.ResultsThe literature search identified 18,334 potential records, and 22 studies involving 3,042,997 pregnant women were ultimately included. Compared with the unexposed group, quetiapine [odds ratio (OR), 1.19; 95% credible interval (CrI), 1.01–1.39], aripiprazole (OR, 1.30; 95% CrI 1.10–1.65), olanzapine (OR, 1.33; 95% CrI 1.11–1.64), risperidone (OR, 1.43; 95% CrI 1.18–1.77), and lithium (OR, 1.61; 95% CrI 1.07–2.30) were associated with a slightly increased risk of congenital malformations. In contrast, lamotrigine (OR, 1.21; 95% CrI 0.86–1.64), ziprasidone (OR, 1.14; 95% CrI 0.73–1.72), and haloperidol (OR, 1.26; 95% CrI 0.90–1.75) did not show significant differences compared with the unexposed group, with narrower credible intervals.ConclusionsThe evidence from this analysis suggests that, overall, quetiapine has the lowest teratogenic risk when used during pregnancy, making it the safer option for pregnant women. Lamotrigine and haloperidol follow closely behind. At the same time, the use of lurasidone and ziprasidone should be approached with caution, and further clinical studies are necessary to better assess their safety.Systematic Review RegistrationPROSPERO CRD4201811373.