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@ARTICLE{SchneiderThoma:285365,
      author       = {Schneider-Thoma, Johannes and Zhu, Yikang and Qin,
                      Mengchang and Dong, Yu and Guan, Shiwei and Wang, Jiaxi and
                      Tian, Jing and Lin, Xiao and Rodolico, Alessandro and
                      Siafis, Spyridon and Bighelli, Irene and Wehner, Melanie and
                      Veith, Christina and Krayer, Felix and Scheuring, Elfriede
                      and Davis, John M and Priller, Josef and Nikolakopoulou,
                      Adriani and Salanti, Georgia and Li, Chunbo and Leucht,
                      Stefan},
      title        = {{C}omparative efficacy and tolerability of antidopaminergic
                      and muscarinic antipsychotics for acute schizophrenia: a
                      network meta-analysis of randomised controlled trials
                      indexed in international {E}nglish and {C}hinese databases.},
      journal      = {The lancet},
      volume       = {407},
      number       = {10531},
      issn         = {0140-6736},
      address      = {London [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2026-00229},
      pages        = {876 - 891},
      year         = {2026},
      abstract     = {Antipsychotic drugs are the established treatment for acute
                      schizophrenia but differ in receptor-binding profiles. In
                      2024, a new-in-class muscarinic receptor agonist
                      (xanomeline-trospium) was licenced, acting upstream of
                      antidopaminergic agents, and providing hope to decrease the
                      adverse effects burden of antipsychotics. We aimed to
                      compare the efficacy and tolerability of antipsychotics by
                      performing network meta-analysis of randomised controlled
                      trials (RCTs).This systematic review (PROSPERO,
                      CRD42022380708) included blinded and open RCTs investigating
                      antipsychotic drugs in participants of any age with acute
                      psychotic symptoms of schizophrenia over 3 weeks to 3
                      months. Included antipsychotics comprised 23 primarily
                      dopamine-receptor blocking medications and the muscarinic
                      receptor agonist xanomeline-trospium in different
                      applications. We searched Cochrane Schizophrenia group's
                      register, previous reviews, and five Chinese databases for
                      trials published from database inception until July 26, 2024
                      and contacted authors to assess trials' methodological
                      quality; only trials with appropriate randomisation
                      indicated were included. The primary outcome was rating
                      scale-measured overall symptoms of schizophrenia (efficacy)
                      analysed with random-effects frequentist network
                      meta-analysis. Secondary outcomes comprised 32 further
                      efficacy and tolerability outcomes. The confidence in the
                      estimates was assessed using the Confidence in Network
                      Meta-Analysis approach.After screening 18 859 references and
                      contacting authors of 5428 trials, we included 438 RCTs. Of
                      those, 388 RCTs with 78 193 participants (28 448 women and
                      49 745 men) provided usable data for at least one outcome.
                      5117 Chinese trials were identified but most were excluded
                      because authors did not reply or reported serious
                      methodological concerns. 256 double-blind studies with 58
                      948 participants provided usable data for the primary
                      outcome. All antipsychotics reduced symptoms more than
                      placebo with standardised mean differences ranging from
                      -0·90 $(95\%$ CI -1·03 to -0·77) to -0·23 (-0·39 to
                      -0·06). Particularly clozapine, as well as amisulpride,
                      olanzapine, and risperidone were more efficacious than at
                      least three other antipsychotics (confidence in estimates
                      were low-to-moderate). Adverse effects varied across
                      medications.This network meta-analysis provides evidence for
                      small-to-medium clinically relevant differences between
                      antipsychotics in efficacy; this finding warrants stronger
                      and more specific emphasis in clinical guidelines.
                      Nonetheless, important differences in tolerability need to
                      be considered for individualised drug choice, with partial
                      dopamine agonists having overall better tolerability and
                      xanomeline-trospium lacking adverse effects of
                      dopamine-blocking agents but resulting in cholinergic and
                      anticholinergic adverse events. Future research should
                      directly compare xanomeline-trospium with other
                      antipsychotics to confirm its efficacy; modern trials using
                      clozapine early in schizophrenia are needed to establish
                      whether it improves outcomes and prevents
                      chronification.German Research Foundation, German Ministry
                      of Research, Technology and Space, and National Natural
                      Science Foundation of China.},
      cin          = {AG Priller},
      ddc          = {610},
      cid          = {I:(DE-2719)5000007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41763745},
      doi          = {10.1016/S0140-6736(25)02365-7},
      url          = {https://pub.dzne.de/record/285365},
}