Paroxetine, a P2X4 inhibitor, prevents cerebral aneurysm growth as well as recanalization after coil embolization of aneurysms: the NHO Drug for Aneurysm Study

Abstract There are no drugs that prevent the growth of cerebral aneurysms or recanalization of aneurysm coil embolization. We have focused on the role of hemodynamics in cerebral aneurysm development and have shown that inhibition of P2X4 purinoceptor, required by vascular endothelial cells to sense blood flow, reduces the induction and growth of aneurysms in animals. A P2X4 purinoceptor inhibitor, paroxetine, is used clinically as an antidepressant. In this study, we therefore investigated the effects of paroxetine on aneurysm growth and postoperative recanalization of coiling. Among cases in the J-ASPECT Study registry, the comprehensive reimbursement database for inpatient care in Japan, we searched for patients taking paroxetine who were registered with a disease name of unruptured aneurysm or had undergone aneurysm coil embolization. Seventy-eight stroke facilities agreed to participate and 275 cases were identified as potentially eligible. Seventy-five enrolled cases met the eligibility criteria: 37 with unruptured aneurysms and 38 after coil embolization. These were compared with 396 controls with unruptured aneurysms and 308 post-coiling controls. Multivariate analysis showed that paroxetine significantly reduced the incidence of aneurysm growth (number of cases with growth/person/year; risk ratio 0.16, 95%CI 0.07–0.37) and the growth length rate (total growth length/person/year; risk ratio 0.46, 95%CI 0.25–0.79). Paroxetine significantly reduced recanalization in the year after coiling (odds ratio 0.22, 95%CI 0.05–0.98). This cohort study suggests that P2X4 inhibitors, including paroxetine, may be clinically applicable as prophylactic agents against rupture by inhibiting cerebral aneurysm growth, and as preventive drugs against postoperative recanalization.