In-hospital predictors of post-stroke depression for targeted initiation of Selective Serotonin Reuptake Inhibitors (SSRIs) - BMC Psychiatry - BMC Psychiatry

Among patients with acute ischemic stroke who presented for follow-up 4–6 weeks post-discharge, history of depression and inpatient PHQ-9 scores were identified as significant in-hospital predictors of PSD. These results suggest that individuals with a history of depression and those reporting depressive symptoms during hospitalization deserve additional consideration for targeted treatment with antidepressants. Depressive symptoms in the inpatient setting are not transient, and should be taken seriously as a risk factor for PSD, which can further exacerbate stroke recovery when left untreated [4]. Our study also suggests that for patients with depressive symptoms during hospitalization, initiation of SSRIs in the post-stroke recovery period may have the potential to reduce depressive symptoms at 4–6 weeks post-discharge. In weighing the risks and benefits of SSRIs in stroke recovery, patients with a history of depression reporting depressive symptoms in the inpatient setting may stand to reap the most benefit from targeted initation of SSRIs.

The predictors of PSD identified in our study extend the literature on previous studies reporting risk factors for PSD. Although history of depression and stroke severity have been identified in previous studies as risk factors for PSD [4, 17,18,19], in-hospital depressive symptoms using the PHQ-9 have not yet been described as a predictor in the literature. Depressive symptoms during hospitalization deserve adequate attention for evaluation and treatment. These symptoms should not be routinely dismissed as a transient reaction to the immediate disabilities precipitated by stroke. In addition, inpatient PHQ-9 score may contribute additional clinical utility since history of depression assessed as a binary variable does not capture the temporality of depressive symptoms leading up to hospitalization for stroke. Including the inpatient PHQ-9 in clinical decision-making may help identify a group of individuals experiencing more severe depressive symptoms that are acutely precipitated by stroke and deserve targeted treatment. Our finding that stroke severity was not significantly associated with post-stroke depression in our multivariable-adjusted model may be explained by the fact that those returning for follow-up had less severe strokes with a smaller range. Although not statistically significant, the trend observed in our study was consistent with previous studies suggesting increased stroke severity as a risk factor for post-stroke depression [4, 17,18,19]. Factors not associated with PSD in our study were also consistent with previous studies; these included older age, sex, stroke subtype, level of education, living alone, marital status, or a previous stroke [17, 18].

Our study suggests that SSRIs may have the potential to improve depressive symptoms at 4–6 weeks post-discharge, adding to the growing body of literature on antidepressant use in stroke recovery. We found that among patients with higher inpatient PHQ-9 scores, initiation of SSRI in the post-stroke setting was associated with greater improvement in PHQ-9 at 4–6 weeks follow-up compared to no SSRI. This trend was not observed among patients with PHQ-9 scores less than 5. Available evidence suggests that pharmacological interventions including SSRIs may prevent depression and improve mood after stroke, although the certainty of evidence is limited to make definitive recommendations on routine prescription of SSRIs [20]. In a randomized controlled trial investigating prevention of depression among patients within three months of stroke onset, the risk of new-onset depression for patients assigned to placebo was more than four times greater than the risk for patients treated with escitalopram [21]. A meta-analysis of 8 randomized RCTs investigating the efficacy of preventive interventions for PSD found that the likelihood of developing PSD was reduced with the use of an SSRI among individuals without depressive symptoms at baseline. Furthermore, there were no significant differences in the frequency of side effects (e.g., nausea, diarrhea, fatigue, and dizziness) between those on active treatment and placebo [22]. In contrast, recent evidence on depression outcomes among patients treated with fluoxetine in the AFFINITY trial found that routine daily treatment with 20 mg fluoxetine did not decrease the proportion of people affected by PSD compared to placebo [23]. Our finding that the improvement in depressive symptoms was notable only for individuals with PHQ-9 greater than or equal to 5 may explain the contrasting result from the AFFINITY trial [23]. In the AFFINITY trial, the mean (SD) PHQ-9 score in the fluoxetine and placebo groups were below 5 at 4.8 (4.3) and 4.9 (4.1), respectively. Stratifying by severity of depressive symptoms in the inpatient setting and selectively initiating SSRIs among patients with higher PHQ-9 scores may help reduce the burden of stroke recovery while minimizing risk of adverse side effects.

Given that the current state of the evidence for SSRIs on PSD does not support routine prescription of SSRIs in stroke recovery, our study lends support for a targeted approach of initiating SSRIs where benefit clearly outweighs the potential risk of harm. Despite the fact that PSD is treatable, the prevalence of PSD has not decreased significantly over the past decade [24]. Therefore, targeted strategies based on clinical predictors of PSD presented in this study are needed. Further research to better understand the duration and dosage of SSRIs needed to maximize benefit in a targeted population may ultimately help reduce rates of PSD.

Our study is not without limitations. We included patients who followed up at a single multidisciplinary stroke center 4–6 weeks post-discharge who were able to complete the PHQ-9. Given significant disability after stroke, these patients are often accompanied by their care partners and need assistance with transportation and other logistical coordination to present to the health care setting. Patients who may not have the necessary social support to navigate the health care system may have been disproportionately lost to follow-up. There may have been selection bias towards the null if patients with more severe strokes or depressive symptoms were lost to follow-up. Conversely, patients who followed up in the outpatient setting may have been those who experienced more difficulty with post-stroke recovery and therefore actively sought medical care. Patients with a history of depression or those who were previously treated with SSRIs may have been more engaged with the health care system in the stroke recovery period. Although we recognize the potential for selection bias in this study, analysis comparing patients with PHQ-9 scores 4–6 weeks post-discharge with those who did not follow-up demonstrated no significant differences in terms past medical history of depression or inpatient PHQ-9 scores. In addition, we did not assess SSRI adherence in this study. We used SSRI mentioned in the follow-up documentation medication list as a proxy for taking an SSRI. Low adherence may have underestimated the impact of SSRIs on PHQ-9 scores 4–6 weeks post-discharge. Although we used data from a prospectively-collected stroke registry, we identified predictors of PSD using a retrospective analysis in a single cohort of acute ischemic stroke patients presenting to a tertiary academic health center. Prospective validation in an external dataset is needed to reliably identify predictors of PSD in other acute ischemic stroke recovery populations. In addition, our inclusion criteria required that patients have the appropriate cognitive abilities to complete the PHQ-9. Given that the prevalence of post-stroke cognitive impairment ranges from 7.4% after a first stroke to 41.3% in recurrent stroke [25], patients with more severe post-stroke cognitive impairment may not have reliably completed the PHQ-9. Lastly, our results are not generalizable to patients with hemorrhagic stroke as we only included patients presenting with acute ischemic stroke. Despite these limitations, our study extends the literature on stroke recovery by identifying predictors of PSD that can be used to better identify and target at-risk individuals for initiation of SSRIs.

Given that PSD is highly prevalent, affecting 1 in 3 individuals during the first year after stroke [24], the ability to predict PSD at time of hospitalization would potentially enable targeted initiation of SSRIs to maximize the benefit of improving mood and minimize the harm associated with side effects. History of depression and inpatient PHQ-9 scores are in-hospital predictors of PSD that can be readily assessed in the inpatient setting to aid clinical decision-making. Furthermore, among patients screening positive for depressive symptoms in the inpatient setting, SSRIs may have the potential to improve depressive symptoms at 4–6 weeks follow-up.

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