Risk of Cerebrovascular Events Associated with Antidepressant Use in Patients with Depression: A Population-Based, Nested Case-Control Study

Chen, Yan; Guo, Jeff J.; Liao, H.-Y.M.; Wulsin, Lawson R.; Patel, Nick C.

doi:10.1345/aph.1k369

Cited by 82 publications

(56 citation statements)

References 35 publications

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“…Conversely, it has been proposed that SSRIs stimulate vasoconstriction via serotonin receptors on vascular smooth muscle (Wu et al, 2011). Regardless of these seemingly contradictory effects on perfusion, these agents have been extensively associated with both cardiovascular disease and cerebrovascular events (Chen et al, 2008;Smoller et al, 2009;Weeke et al, 2012;Whang et al, 2009;Wu et al, 2011). The two studies that specifically examined the effect of SSRIs on WMHs both found an increase in WMHs among SSRI-treated patients, but only one demonstrated a statistically significant relationship (Grool et al, 2013;Steffens et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Khalaf

Edelman

Tudorascu

et al. 2015

Neuropsychopharmacol

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White matter hyperintensities (WMHs) have been shown to be associated with the development of late-life depression (LLD) and eventual treatment outcomes. This study sought to investigate longitudinal WMH changes in patients with LLD during a 12-week antidepressant treatment course. Forty-seven depressed elderly patients were included in this analysis. All depressed subjects started pharmacological treatment for depression shortly after a baseline magnetic resonance imaging (MRI) scan. At 12 weeks, patients underwent a follow-up MRI scan, and were categorized as either treatment remitters (n = 23) or non-remitters (n = 24). Among all patients, there was as a significant increase in WMHs over 12 weeks (t(46) = 2.36, P = 0.02). When patients were stratified by remission status, non-remitters demonstrated a significant increase in WMHs (t(23) = 2.17, P = 0.04), but this was not observed in remitters (t(22) = 1.09, P = 0.29). Other markers of brain integrity were also investigated including whole brain gray matter volume, hippocampal volume, and fractional anisotropy. No significant differences were observed in any of these markers during treatment, including when patients were stratified based on remission status. These results add to existing literature showing the association between WMH accumulation and LLD treatment outcomes. Moreover, this is the first study to demonstrate similar findings over a short interval (ie 12 weeks), which corresponds to the typical length of an antidepressant trial. These findings serve to highlight the acute interplay of cerebrovascular ischemic disease and LLD.

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Section: Discussionmentioning

confidence: 99%

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Khalaf

Edelman

Tudorascu

et al. 2015

Neuropsychopharmacol

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“…Conversely, evidence from observational studies suggested an increased risk of stroke in relation to treatment with antidepressants. 39,40 However, these findings should be treated with cautions because of the possible confounding by indication (depression severity). In other words, patients treated with antidepressants are more likely to have severe depressive symptoms, and the observed increased risk of stroke may be attributable to depression severity rather than the antidepressant use.…”

Section: Dong Et Al Depression and Risk Of Stroke 33mentioning

confidence: 99%

Depression and Risk of Stroke

Dong

Zhang

Tong

et al. 2012

Stroke

263

108

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Background and Purpose-A history of depression may be associated with an increased risk of stroke. We aimed to determine the association between depression and risk of stroke by performing a meta-analysis of prospective studies. Methods-Relevant studies were identified by a PubMed database search through May 2011 without restrictions and by reviewing reference lists of obtained articles. Community-based or population-based prospective studies that reported relative risk estimates with 95% confidence intervals for the association between depression and stroke were selected. Studies that enrolled participants with preexisting stroke at baseline were excluded. A random-effects model was used to compute the pooled risk estimate. Results-Random-effects meta-analysis of 17 prospective studies involving 206 641 participants and 6086 cases demonstrated a significant positive association between depression and subsequent risk of stroke (pooled relative risk, 1.34; 95% confidence interval, 1.17-1.54) after adjustment for potential confounding factors. The associations were similar between men and women. Potential publication bias may exist, but correction for this bias using a formal statistical method did not materially alter the combined risk estimate. Conclusions-Depression significantly increased the risk of development of stroke, and this increase was probably independent of other risk factors, including hypertension and diabetes. (Stroke. 2012;43:32-37.)

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“…Two previous studies showed an increased risk of ischemic stroke in current SSRI users. 16,24 This increased risk could be explained by a different biological mechanism, which postulates that serotonin induces vasoconstriction of large vessel, and may lead to thromboembolic ischemic stroke in the presence of atherosclerosis. 52 However, in our study, we focused on silent ischemic vascular lesions, involving the small cerebral arteries, which are typically not caused by thromboembolic events.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9] SSRIs block the reuptake of serotonin by platelets and decrease serotonin platelet concentration, which may lead to impaired aggregation and prolonged bleeding times. [10][11][12][13][14] SSRIs have, therefore, extensively been studied in relation to intracerebral hemorrhages, [15][16][17][18][19][20][21][22] and a recent meta-analysis of controlled observational studies showed an increased risk of intracerebral hemorrhages in SSRI users compared with nonusers. 23 In addition, via the same pathophysiological pathway of reducing platelet aggregation, antidepressants with a high inhibition for serotonin reuptake may also reduce the risk of ischemic stroke, although to date this hypothesis is scarcely supported by literature.…”

Section: See Related Article P 1917mentioning

confidence: 99%

“…23 In addition, via the same pathophysiological pathway of reducing platelet aggregation, antidepressants with a high inhibition for serotonin reuptake may also reduce the risk of ischemic stroke, although to date this hypothesis is scarcely supported by literature. 15,16,21,24,25 Apart from major cerebrovascular events, it has not yet been investigated whether SSRIs or strong inhibitors of serotonin reuptake are associated with subclinical cerebrovascular lesions and more particularly with subclinical bleedings. Cerebral microbleeds have increasingly been recognized on MRI in stroke patients and mostly in association with larger intracerebral hemorrhages.…”

Section: See Related Article P 1917mentioning

confidence: 99%

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Inhibition of Serotonin Reuptake by Antidepressants and Cerebral Microbleeds in the General Population

Aarts

Akoudad

Noordam

et al. 2014

Stroke

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Background and Purpose-Serotonin reuptake inhibiting antidepressants decrease platelet aggregation. This may cause an increased risk of intracerebral hemorrhage. However, the risk of subclinical microbleeds, which are highly prevalent in middle-aged and elderly people, is unknown. We studied whether serotonin reuptake inhibiting antidepressants increase the frequency of cerebral microbleeds and secondarily whether they lower the presence of ischemic vascular damage.

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Risk of Cerebrovascular Events Associated with Antidepressant Use in Patients with Depression: A Population-Based, Nested Case-Control Study

Cited by 82 publications

References 35 publications

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Depression and Risk of Stroke

Inhibition of Serotonin Reuptake by Antidepressants and Cerebral Microbleeds in the General Population

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