Intracranial haemorrhage and use of selective serotonin reuptake inhibitors

Aims In the past few years an increasing number of bleeding disorders have been reported in association with the use of selective serotonin reuptake i nhibitors (SSRIs), including serious cases of intracranial haemorrhage, rai sing concerns about the safety of this class of drugs. The present study wa s performed to test the hypothesis of an increased risk of intracranial hae morrhage associated with the use of SSRIs. Methods We carried out a case-control study nested in a cohort of antidepre ssants users with the UK-based General Practice Research Database (GPRD) as the primary source of information. The study cohort encompassed subjects a ged between 18 and 79 years who received a first-time prescription for any antidepressant from January, 1990 to October, 1997. Patients with presentin g conditions or treatments that could be associated with an increased risk of intracranial haemorrhage were excluded from the cohort. Patients were fo llowed-up until the occurrence of an idiopathic intracranial haemorrhage. U p to four controls per case, matched on age, sex, calendar time and practic e were randomly selected from the study cohort. We estimated adjusted odds ratios and 95% confidence intervals of intracranial haemorrhage with curren t use of SSRIs and other antidepressants as compared with nonuse using cond itional logistic regression. Results We identified 65 cases of idiopathic intracranial haemorrhage and 2 54 matched controls. Current exposure to SSRIs was ascertained in 7 cases ( 10.8%) and 24 controls (9.7%) resulting in an adjusted OR (95%CI) of 0.8 (0 .3,2.3). The estimate for 'other antidepressants' was 0.7 (0.3,1.6). The ef fect measures were not modified by gender or age. No effect related to dose or treatment duration was detected. The risk estimates did not change acco rding to the location of bleeding (intracerebral or subarachnoid). Conclusions Our results are not compatible with a major increased risk of i ntracranial haemorrhage among users of SSRIs or other antidepressants at la rge. However, smaller but still relevant increased risks cannot be ruled ou t.