Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators
Marco Solmi, Giovanni Croatto, Arnav Gupta, Nicholas Fabiano, Stanley Wong, Michele Fornaro, Lynne Kolton Schneider, S. Christy Rohani-Montez, Leanne Fairley, Nathalie Smith, István Bitter, Philip Gorwood, Heidi Taipale, Jari Tiihonen, Samuele Cortese, Elena Dragioti, Ebba Du Rietz, René Ernst Nielsen, Joseph Firth, Paolo Fusar‐Poli, Catharina A. Hartman, Richard I. G. Holt, Anne Høye, Ai Koyanagi, Henrik Larsson, Kelli Lehto, Peter Lindgren, Mirko Manchia, Merete Nordentoft, Karolina Skonieczna‐Żydecka, Brendon Stubbs, Davy Vancampfort, Michele De Prisco, Laurent Boyer, Eduard Vieta, Christoph U. Correll
Abstract
To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.