Use of SSRIs Not Associated with Increased Bleeding Events in Children: An Analysis of the Michigan Medicaid Database from 2000–2003
Authors: Powell Kerry K , Wang Wei , Kelleher Kelly J , O’Brien Sarah H 
Published: April 2020

Abstract
Background and Aim : Serotonin reuptake inhibitors (SSRIs) have been used in children for a variety of psychiatric illnesses including depression, anxiety and eating disorders. In adults, there have been several studies demonstrating an association between SSRIs and increased bleeding events, particularly gastrointestinal bleeds. It is thought that SSRIs affect platelet aggregation by inhibiting serotonin uptake by platelets, resulting in decreased intra-platelet serotonin concentration. To date there are no pediatric studies evaluating bleeding risk in children taking SSRIs. The objective of this study was to evaluate the incidence of bleeding events in children who are prescribed SSRIs
Methods : We performed a review of the Michigan Medicaid database from 2000–2003 and identified all children ages 0–18 years prescribed six commonly used SSRIs: citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine and sertraline. Children prescribed Attention deficit hyperactivity disorder (ADHD) or antipsychotic medications were used as comparison groups. We obtained demographic data including age, gender and race for individuals with both SSRI prescriptions and bleeding events. Bleeding events were defined according to previously published definitions for major and minor bleeding using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) diagnostic codes. Bleeding events must have occurred within 90 days of an SSRI prescription. For individuals with bleeding events, we evaluated all inpatient, outpatient and long term records during the 6 months before and after the event. We compared the incidence of bleeding events in the SSRI, ADHD, and antipsychotic medication groups by using Proc GENMOD in SAS 9.1.3. This accounted for the fact that there were patients on multiple medications. We found no statistical difference in the total number of bleeding events between the three medication categories.
Results : Of 20,631 children prescribed SSRIs in the study population, six children experienced bleeding events (Table 1). The incidence of bleeding was 29 in 100,000 persons. Two events were associated with traumatic injuries and one was observed in a critically ill patient. There were 52,050 children on ADHD medication and 17,340 on atypical antipsychotics. The incidence of bleeding events in these groups was 13 in 100,000 and 40 in 100,000 respectively. Of note, two of six children in the SSRI group with bleeding events were also prescribed ADHD medication.
TABLE 1
Patient Age (years) Gender Race Bleeding Event Associated Diagnosis 1 11.3 Male Black Intracerebral hemorrhage Subdural hemorrhage Lymphoid leukemia Sepsis Aspergillosis Acute respiratory failure Acute renal failure Perforation of intestine Adjustment disorder 2 12.3 Male White Hematoma-complication of procedure Femur fracture Closed reduction of fracture ADHD with hyperactivity Depressive disorder 3 13.4 Female White Subarachnoid hemorrhage Extradural hemorrhage Closed fracture base of skull Convulsive disorder Developmental delay 4 17.7 Female White Subdural hemorrhage ADHD with hyperactivity Intracranial injury 5 17.5 Female White Hemorrhage complicating a procedure Acute pharyngitis and tonsillitis Tonsillectomy 6 15.4 Female White Subdural hemorrhage Cerebral palsy Spastic hemiplegia
Discussion : We found that the incidence of bleeding events in children taking SSRIs is not increased as compared to those taking ADHD and antipsychotic medication. The majority of bleeding events that occurred in the 6 children prescribed SSRIs were either associated with trauma or a known complication of a surgical procedure. There were no gastrointestinal bleeding events in the SSRI group. Our study suggests that the use of SSRIs does not confer an increased risk of abnormal bleeding events in children.