Post-Stroke Depression


Maju Mathews, MD, MRCPsych, Dip Psych, Manu Mathews, MD, Kumar Budur, MD, Dip Psych, Vinu George, MD, Joanne Mathews, MD, and Shiny Abraham, MD


Pages 35 - 38

Psychiatric Complications of Stroke

Many of the studies addressing post-stroke depression (PSD) have arrived at different conclusions. Pseudodepressive mood disorders are often classified simply as depression.

These pseudodepressive manifestations, which occur shortly after a stroke, include emotionalism, catastrophic reaction, pathological crying, anxiety, apathy, and loss of psychic self-activation.4

Some of the studies lump together acute and chronic complications of stroke; for example, mania or mania-like states and catastrophic reactions are seen early in the course of stroke, whereas depression is usually a chronic manifestation.

The Lausanne Emotion in Acute Stroke Study4 examined at the various emotional manifestations following stroke in over 300 patients and found that overt sadness was the most common manifestation (72%), followed by disinhibition (56%), lack of adaptation (44%), emotional withdrawal (40%), crying (27%), anosognosia (24%), passivity (24%), and aggressiveness (11%).

Depression is the main mood disorder seen in the nonacute phase. It is difficult to assess for features of depression, such as lack of interest, lack of pleasure in activities, or loss of self-esteem in patients in intensive care units; hence, it is more appropriate to speak of sadness or behavioral changes in the acute phases than of clinical depression.

Depression following stroke shows important clinical differences from “endogenous depression,” as patients have much more reactive diurnal mood variation and emotionalism, show an absence of guilt, and are rarely suicidal, despite the fact that they are also disabled from a physical point of view. However, the death rate is increased in patients who are depressed following a stroke.5-10

Post-stroke depression has a negative impact on functional outcome, and there is a strong correlation between development of depression, social functioning, and overall quality of life for stroke survivors. This is complicated by the fact that depression can lead to a worse functional outcome and vice versa. Depression also causes a significant increase in the risk of death following a stroke, with cardiac causes being more implicated than other causes.

Various subjective and objective measures have been used in different studies in the assessment of PSD. Among them are the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-Rating Depression Scale, Center for Epidemiological Studies Depression (CES-D) scale, and the Diagnostic and Statistical Manual of Mental Disorders, third and fourth editions (DSM-III and DSM-IV).

Risk Factors

Increased incidence of PSD is associated with female sex,11 family history or past history of psychiatric problems (particularly depression),12 subcortical lesions,13 younger age,14 impaired social support (especially from spouse), negative life events,15 and living at home within 1 month of a stroke. A positive correlation between the level of functional impairment and PSD has also been noted, particularly within 1 month following stroke. Patients with high neuroticism scores have a higher rate of developing PSD than those with low neuroticism scores.16

Depression is also associated with dementia and more severe strokes, particularly in vascular territories that supply limbic structures. Reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnosis of depression after ischemic stroke.17

Site of brain lesion

A number of studies have examined the relationship between depression and laterality of brain lesion. Some of the earlier studies showed that left-sided lesions are associated with increased incidence of PSD.18,19 Another study concluded that the proximity of the lesion to the inferior frontal region of the hemisphere, irrespective of the side, is associated with increased incidence of PSD.20 A review of 25 studies that examined the relationship between depression and brain laterality noted that 14 of them showed no predisposition to any particular side, eight showed increased predisposition to the left side, and three studies showed increased predisposition to the right side.21 An earlier review had also failed to find an association between left-sided lesion and PSD.22

Robinson23 has emphasized that the strokes leading to major and minor depression may have different locations. The timing of assessment may also be critical, with depressive features in the acute phase being correlated to a lesion in the left frontal region, whereas in the longer term they correlate with lesions closer to the occipital pole in the right hemisphere.

The Lausanne Emotion in Stroke Study found that the predictive value of early changes is poor, as the patients who go on to develop depression in the chronic phase are not necessarily those who show the most important signs of behavioral depressive changes in the acute phase. Only 10% of patients with depression at one year had shown severe sadness during the acute phase. Most cases of PSD showed a strong association with lesions in the subcortical white matter, thalamus, basal ganglia, and brain stem, rather than cortical damage with specific cognitive disturbance.24

It has also been postulated that stroke results in an inability to experience positive emotions, which in turn leads to depression.

Post-stroke fatigue

Fatigue is a feature of depression; however, it can also occur without depression. Fatigue after stroke is a neglected but major problem. Patients with post-stroke fatigue (PSF) do not show either very severe neurological disturbance or functional impairment. These patients have often recovered well from their stroke without any subsequent hemiparesis or cognitive disturbance, but are still unable to return to work because of severe fatigue.

It has been suggested that patients with primary PSF have mainly brain stem lesions. They may also have subtle attentional dysfunction, although neuropsychological assessments have shown no cognitive-executive disturbances.25

Importance of recognition of PSD

Recognition of PSD is very important, as patients with depression following stroke have greater impairment of activities of daily living (ADLs) than do patients without depression. Post-stroke patients followed up for 2 years who showed remission of symptoms of PSD also showed improved recovery in ADLs.26 Depression is also associated with cognitive impairment, and treatment is associated with improvement in the cognitive abilities and maintenance of the improvement.27 There is also a significantly increased risk of death following PSD. A 10-year follow-up study found that the most common cause of death was cardiac (44%), followed by repeat strokes (28%). Treatment results in a reduction in mortality. The risk of suicide in PSD is increased as well.


A significant proportion of patients with PSD may resolve spontaneously, suggesting that a reactive element may be the cause of depression, particularly in the immediate post-stroke period. The later the onset of depression after stroke, the less likely that it will resolve spontaneously.

There are very few controlled studies addressing the treatment of PSD. Trials of antidepressants have found that tricyclic antidepressants such as nortriptyline are effective in treating this condition.28 One of the largest trials, involving citalopram, showed it to be effective in relieving symptoms of PSD in up to 65% of patients.29 A more recent study comparing nortriptyline with fluoxetine and placebo found that nortriptyline at doses of up to 100 mg per day was significantly superior to fluoxetine or placebo.30 However, another study has shown fluoxetine to be an efficacious and well-tolerated treatment for PSD.31

There is no consensus regarding the role of prophylactic antidepressants in preventing the emergence of depression. Two studies that have been conducted have found opposing results, with one suggesting that the early initiation of antidepressant therapy does not prevent the emergence of PSD,32 and the other showing that nortriptyline and fluoxetine are effective as prophylactic agents in the immediate post-stroke period when given for 12 weeks to patients without depression. However, depression was more likely to develop in the patients later upon discontinuation of antidepressants than it was in those given placebo.33

Regarding psychological therapies, there is again a dearth of studies. One study, however, concluded that cognitive behavioral therapy was not effective in the treatment of PSD.34


Depression following stroke has an impact on ADLs, cognitive function, and mortality. Treatment results in a significant improvement in outcomes. More research is needed to determine effective interventions for this condition. Health professionals involved in treating stroke patients need to be more aware of this condition.