Hemorrhagic stroke associated with antidepressant use in patients with depression: does degree of serotonin reuptake inhibition matter?
OBJECTIVE
This study aimed to determine whether the degree of serotonin (5-HT) reuptake inhibition affects risk of hemorrhagic stroke associated with antidepressant use in patients with depression.


METHODS
A population-based, nested case-control study was performed using a managed care medical claims database. Ninety two depressed patients with a diagnosis of hemorrhagic stroke were identified and matched with 552 controls by age, sex, and year of index date of depression (IDD). Diagnoses of depression, hemorrhagic stroke, and other medical comorbidities were identified using ICD-9 codes. Antidepressants were classified as high, medium, or low reuptake inhibition based on their affinities for the 5-HT reuptake transporter, determined using their respective equilibrium dissociation constants (K(D); high: K(D) < 1 nM; medium: 1 <or= K(D) < 10 nM; low: K(D) >or= 10 nM). Conditional logistic regression analysis was performed to estimate the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of the risk of hemorrhagic stroke.


RESULTS
Compared to non-users of antidepressants, risk of hemorrhagic stroke did not significantly differ between patients who had ever used antidepressants with high (OR = 0.82; 95% CI = 0.44-1.55), medium (OR = 0.93; 95% CI = 0.37-2.31), or low (OR = 0.38; 95% CI = 0.11-1.41) 5-HTT inhibition.


CONCLUSIONS
Risk of hemorrhagic stroke associated with antidepressant use may not be related to an antidepressant's degree of 5-HT reuptake inhibition. Given the limitations of this study, additional studies are needed to confirm these findings.
Chen
Yan
Y
Division of Pharmacy Practice and Administrative Sciences, University of Cincinnati Medical Center, Cincinnati, OH 45267-0004, USA. Yance@email.uc.edu
Guo
Jeff J
JJ
Patel
Nick C
NC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D016208:Databases, Factual; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors