Inhibition of Serotonin Reuptake by Antidepressants and Cerebral Microbleeds in the General Population

Abstract

Background and Purpose-Serotonin reuptake inhibiting antidepressants decrease platelet aggregation. This may cause an increased risk of intracerebral hemorrhage. However, the risk of subclinical microbleeds, which are highly prevalent in middle-aged and elderly people, is unknown. We studied whether serotonin reuptake inhibiting antidepressants increase the frequency of cerebral microbleeds and secondarily whether they lower the presence of ischemic vascular damage.

Association between haemorrhages and treatment with selective and non-selective serotonergic antidepressants: Possible implications of quantitative signal detection

“…Underreporting (Martin et al, 1998), the phenomenon of insufficient awareness of a possible association between drug treatment and occurrence of an ADR or unwillingness to report an ADR, might be the main reason. Secondly, considering that the risk of bleeding is presumably only slightly increased under treatment with SSRI (Andrade et al, 2010;Aarts et al, 2014), methods of pharmacovigilance (i.e. signal detection analyses using pharmacovigilance databases) might be insufficiently sensitive for detecting rarely occurring ADR such as drug-related haemorrhages.…”

A novel HTRA1 exon 2 mutation causes loss of protease activity in a Pakistani CARASIL patient

“…Although this affects an amino acid residue outside the protease domain (i.e., in a short interdomain region connecting the Kazal-type and protease Fig. 1 Family tree domains), we demonstrate that it prevents protease activity, indicating a loss-of-function mechanism [10] in CARASIL. Further work will elucidate the contribution of the targeted residue, and this domain, to HtrA1 activity.…”

Selective Serotonin Reuptake Inhibitors and Risk of Cerebral Bleeding

“…Previous exposure to antidepressants with high affinity for the serotonin transporter and strong serotonin reuptake inhibition was not associated with an increased prevalence of previous cerebral microbleeds or a lower prevalence of previous ischemic brain lesions because of small-vessel disease, as hypothesized. 12 The results of the study of Aarts et al 12 are consistent with the null hypothesis that there is no significant causal relationship between exposure to SSRIs and risk of hemorrhagic and ischemic brain lesions in the general population. However, there are several methodological caveats to this study, as discussed by the authors.…”

“…Usage of single antidepressants before the MRI was obtained from continuously monitored computerized pharmacy records (ascertainment >99%). 12 Aarts et al 12 found that 930 (18.8%) persons had a history of antidepressant use before MRI, of whom 311 (6.2%) exclusively used antidepressants with a high degree of serotonin reuptake inhibition (paroxetine, clomipramine, sertraline, duloxetine, fluoxetine). Cerebral microbleeds were detected in 957 individuals (19.4%), of whom 53 (5.5%) used antidepressants with a high degree of serotonin reuptake inhibition.…”