Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity

Abstract

IMPORTANCESelective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms. OBJECTIVE To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms. DESIGN, SETTING, AND PARTICIPANTSLongitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke. MAIN OUTCOMES AND MEASURESWe conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH;(2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity. RESULTSMean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors.CONCLUSIONS AND RELEVANCE Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.

Latent profile analysis of cognitive decline and depressive symptoms after intracerebral hemorrhage

“…Cognitive decline and depression onset are both associated with poor long-term functional outcomes following stroke in general, and ICH in particular [4][5][6][7][8]. Multiple studies, including from our group, also clarified that cognitive decline and depressive symptoms often overlap among ICH survivors [3,9].…”

“…Study staff augmented phone-based follow-up data with semi-automated review of longitudinal electronic medical records [9]. We specifically extracted data on use of antidepressant medications, based on previously described methods [3].…”

“…We defined incident dementia for outcome analyses as patients meeting both of the following criteria: 1) relevant ICD-9 or ICD-10 codes entered in electronic medical records; and 2) diagnosis confirmed by semi-automated review of medical records, as previously described [27]. We defined depression for outcome analyses as patients meeting both of the following criteria: 1) relevant ICD-9 or ICD-10 codes entered in electronic medical records; and 2) diagnosis confirmed by semi-automated review of medical records, as previously described [3].…”

“…Survivors of Intracerebral Hemorrhage (ICH) are at high risk for cognitive decline following the acute hemorrhage event, with up to 40% of patients developing dementia within 5 years [1]. Between one third and half of all ICH survivors also develop post-stroke depression within 5 years of the initial hemorrhagic stroke [2,3]. Cognitive decline and depression onset are both associated with poor long-term functional outcomes following stroke in general, and ICH in particular [4][5][6][7][8].…”

The efficacy of Tuina with herbal ointment for patients with post-stroke depression: study protocol for a randomized controlled trial

“…The PSD clinical medication guidelines lack high-quality evidence-based support, which makes it difficult for clinicians to determine the medication regimen [9]. In addition, first-line antidepressant exposure after intracerebral hemorrhage (ICH) is associated with increasing risk of recurrent hemorrhagic stroke [10]. Therefore, more patients prefer to use complementary and alternative therapies for PSD [11].…”