Stroke treatment occurs across a spectrum consisting of various phases. One of these phases is the rehabilitation phase, where the primary focus is to optimally recover from stroke and improve quality of life. SSRIs are most frequently used in this setting to accomplish the goals of this phase. The physiatrist will evaluate the patient’s functional capabilities and with a team that includes therapists and nursing staff, they will execute a comprehensive plan for recovery. This plan must prioritize the deficits for the most efficient integration to society while monitoring for any medical complications.

Administration of SSRIs to stroke patients has been shown to improve their overall mortality. This was first demonstrated in a study by Jorge et al. In that study, they enrolled 104 patients who were randomly assigned to receive a 12-week double-blind course of the nortriptyline (tricyclic antidepressant), fluoxetine (SSRI), or placebo early in the recovery period after a stroke [2]. Mortality data were obtained from the patients for 9 years after initiation of the study and analyzed using Kaplan-Meier survival curves. Of the 53 patients who were given full-dose antidepressants, 36 (67.9 %) were alive at follow-up, compared with only 10 (35.7 %) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled [2]. Based on these results, the authors concluded that treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months post-stroke significantly increased the survival of both depressed and nondepressed patients.

Along similar lines, a more recent study has demonstrated improvement in overall disability. Mikami et al. enrolled 83 post-stroke patients in a double-blind randomized trial, which examined the efficacy of antidepressants in treating depressive disorders and reducing disability. Subjects were given one of the three interventions: fluoxetine, nortriptyline, or placebo. The modified Rankin scale (mRS) was used to evaluate the disability of patients and activities of daily living impairments were assessed by the Functional Independence Measure (FIM). In the study, patients who received fluoxetine or nortriptyline had significantly greater improvement in mRS scores compared to patients who received placebo [3]. This effect was independent of depression, suggesting that antidepressants may facilitate the neural mechanisms of recovery in patients with stroke. It is also important to note that the recovery in subjects given antidepressants continued throughout the 12 months, despite cessation of treatment at 3 months; this continued recovery was not seen in subjects who received placebo.

The exact reasons for the improvement are unclear but there are some possible explanations. At first glance, one might explain the findings through PSD. As will be discussed later, PSD is quite prevalent and can adversely affect recovery and impair quality of life. Thus by placing stroke victims on antidepressants, physicians treat PSD and indirectly improve outcomes in this method. However this does not explain all the findings. A key point to highlight in these studies is that even stroke survivors who were not diagnosed with depression still received benefit from these medications.

Other possible mechanisms of post-stroke recovery include neuroplastic mechanisms. There is a large amount of literature on the role of neuroplasticity on functional reorganization and recovery following stroke [4–7]. Yet another proposed mechanism is through inhibition of the microglial production of proinflammatory cytokines by SSRIs [8]. Further research is required to elucidate the exact mechanisms by which SSRIs improve functional outcomes and mortality following a stroke. The antidepressant effects and its role will be discussed in more detail below.

PSD is unfortunately common and impedes stroke survivors’ path to recovery. The average prevalence is 30 %, although it has been found to be up to 63 % across individual studies [9, 10]. Half of these diagnoses represent major depressive disorder. A pooled observational study found that this rate remained relatively constant averaging 33 % when examined at 1 month, 1–6 months, and greater than 6-month intervals [11]. Another study found prevalence to vary over time, peaking at 3–6 months with a subsequent decline at 1 year to about 50 % of initial rates. This study also suggested that depressive symptoms can be classified into post-stroke major depressive disorder, which tends to remit spontaneously and post-stroke dysthymia which tends to persist at 1–2 years [12]. This subclassification phenomenon has not been reproduced in subsequent studies. Notably, these studies followed the natural history without the administration of any interventions. This demonstrates that PSD is highly prevalent and often remits spontaneously despite treatment, but persists in a significant portion of patients.

The underlying mechanism in the development of PSD is multifactorial. Possible mechanisms include increased activity in the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic stimulation, proinflammatory cytokine levels, diminished adherence to medical treatment, neglect of self-care, inactivity, poor diet, and substance use [13]. Most current studies focus on the pathological changes caused by injury to neural networks as well as poor adjustment to new disability.