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SSRIs associated with increased risk of brain haemorrhage, but absolute risks low

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Question: Is there an association between selective serotonin reuptake inhibitors (SSRIs) and the incidence of brain haemorrhage?

Outcomes: Incidence of intracerebral haemorrhage, intracranial haemorrhage, subarachnoid haemorrhage or haemorrhagic stroke (subarachnoid haemorrhage plus intracerebral haemorrhage).


Design: Systematic review with meta-analysis.

Data sources: MEDLINE, EMBASE, Web of Science Conference Proceedings, SCOPUS, ProQuest and dissertations were searched for controlled observational studies (search dates not stated). Reference lists of identified studies were hand searched.

Study selection and analysis: Studies were included if they had a control group not taking SSRIs and were a prospective or retrospective cohort study, case–crossover or case–control study reporting risks of brain haemorrhage associated with SSRIs. Study results were pooled using DerSimonian and Laird fixed effect rate ratios. Results from adjusted and unadjusted analyses were pooled separately. Random effects models were used for sensitivity analysis. Heterogeneity was assessed using the I2 statistic. Duval-and-Tweedie trim-and-fill analyses were used to assess the possibility of publication bias. Risks of haemorrhage with exposure …

Correspondence to Mathison Centre for Mental Health Research and Education, Rm # 4D64, TRW Building, 3280 Hospital drive NW, Calgary, Alberta, Canada T2N4Z6; rramasub{at}

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