Background and Purpose-Selective serotonin reuptake inhibitors (SSRIs) have been associated with increased risk of bleeding complications, possibly as a result of inhibition of platelet aggregation. Little is known about the risk of intracerebral hemorrhage in users of SSRIs and whether the effect on platelet aggregation reduces the risk of ischemic stroke. We used population-based data to estimate the risk of hemorrhagic and ischemic stroke in users of SSRIs. Methods-We performed a nested case-control study in Funen County (465 000 inhabitants), Denmark. All patients with a first-ever stroke discharge diagnosis in the period of 1994 to 1999 were identified, and a validated diagnosis of stroke was reached in 4765 cases. In all, 40 000 controls were randomly selected from the background population. Information on drug use for cases and controls was retrieved from a prescription registry with full coverage of the county. Odds ratios were adjusted for age, sex, calendar year, and use of other medication. To evaluate the effect of various potential confounders not recorded in the register data, we performed separate analyses on data from 2 large population-based surveys with more detailed information on risk factors. Results-Of 659 patients with hemorrhagic stroke, 21 were current users of SSRIs. The adjusted odds ratio of hemorrhagic stroke in current SSRI users compared with never users was 1.0 [95% confidence interval (CI), 0.6 to 1.6]. Of 2717 patients with ischemic stroke, 100 were current users of SSRIs, and the adjusted odds ratio of ischemic stroke in cases compared with controls was 1.1 (95% CI, 0.9 to 1.4). The survey data indicated that additional confounder control would not have led to an increase in the relative risk estimates. Conclusions-Current exposure to SSRIs is not associated with increased risk of intracerebral hemorrhage and is probably not associated with a decreased risk of ischemic stroke.

The purpose of this study was to compare the effect of hyperventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored continuously. Within the first four days after the trauma the CO(2) and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous (133)Xe technique) and arterio-venous difference of oxygen (AVdO(2)). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO(2)), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated. Before intervention ICP was well controlled ,(14.8 (9-24) mmHg) and basic CBF level was 39.1 (21.6-75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO(2) = 4.3 (1.8-8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO(2) were decreased (1.54 (0.7-3.2) ml/100 g/min) as well. During hyperventilation (delta PaCO(2)=0.88 (0.62-1.55) kPa) CBF decreased with 11.8 (-33.4-29.7) %/kPa and ICP decreased with 3.8 (0-10) mmHg. AVdO(2) increased 34.0 (4.0-139.2) %/kPa, MABP was unchanged, CMRO(2) and CPP increased (delta CPP = 3.9 (-10-20) mmHg). AVD (lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed. An i.v. bolus dose of indomethacin (30 mg) decreased CBF 14.7 (-16.7-57.4)% and ICP decreased 4.3 (-1-17) mmHg. AVdO(2) increased 27.8 (-40.0-66.7)%, MABP (delta MABP = 4.9 (-2-21) mmHg) and CPP (delta CPP = 8.7 (3-29) mmHg) increased while CMRO2 was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found. Compared to hyperventilation (changes per 1 kPa, at PaCO(2) level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO(2), ICP, SvjO(2) and LOI were of the same order of magnitude. No correlation between relative reactivities to indomethacin and CO(2), evaluated from changes in CBF and AVdO(2), or between the decrease in ICP after the two procedures were found. Thus, some patients reacted to indomethacin but not to hyperventilation, and vice versa. These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.