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Major depressive disorder increases the risk of stroke indirectly through the development of major metabolic comorbidities and greater severity of depressive symptoms, rather than through the use of antidepressant medications. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 8, 2012Open Access

Major Depressive Disorder and Stroke Risks: A 9-Year Follow-Up Population-Based, Matched Cohort Study

Structured PICO

Does a clinical diagnosis of major depressive disorder increase the risk of stroke in a general population?

Population

5,015 subjects from Taiwan's National Health Insurance database, including 1,003 patients with at least 2 diagnoses of Major Depressive Disorder (MDD) and 4,012 well-matched normal controls (1:4 ratio). Mean age ~41.2 years, 36.6% male. Excluded: bipolar disorders, affective psychosis, and baseline major metabolic diseases or stroke.

Intervention

Clinical diagnosis of Major Depressive Disorder (MDD), with subgroups stratified by baseline refractoriness to antidepressants (easy to treat, intermediate difficult to treat, and difficult to treat).

Comparator

Well-matched normal control subjects without a diagnosis of MDD or bipolar disorder.

Outcome

Newly-developed strokes (identified using ICD-9-CM codes 430.X-438.X for hemorrhagic, ischemic, and other types) over a maximum 9-year follow-up.hard clinical

A clinical diagnosis of major depressive disorder increases stroke risk indirectly through the development of major metabolic comorbidities and more intense depressive symptoms, rather than directly or via antidepressant use.

Abstract

BACKGROUND AND PURPOSE: Major depressive disorder (MDD) is characterized by recurrent depressive episodes and one of the treatment choices is antidepressants. Patients with MDD are at greater risk of developing major metabolic diseases that may in turn lead to stroke. Moreover, both depressive symptoms and taking antidepressant medications are associated with higher risk of stroke. However, whether and how clinical depression increases stroke risk remains an unanswered question. Our aim was to provide answers to this question. METHODS: A matched cohort study of 5015 subjects (1003 MDD patients and 4012 control subjects) was conducted using a nationwide database. Subjects were followed to a maximum of 9 years to determine rates of newly-developed strokes, and controls and MDD groups with different levels of antidepressant refractoriness were compared to determine the temporal relation between stroke and three major metabolic comorbidities (i.e., diabetes mellitus, hypertension and hyperlipidemia). The levels of depressive symptoms and the antidepressant medications before stroke onset were investigated. RESULTS: Patients with MDD had significantly higher rates of stroke (4.3% vs. 2.8%, p<0.05) during the follow-up. Mediation regression analyses revealed that the occurrence of stroke in the MDD subjects was significantly mediated by the development of major metabolic diseases. Greater severity of depression, but not greater use of antidepressants, preceded the occurrence of stroke. CONCLUSIONS: A clinical diagnosis of major depression leads to stroke indirectly through more intense depressive symptoms and the development of major comorbidities.

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