Definitions and Descriptions
Depression following stroke: Within this module, we consider depression following stroke. The DSM5 category that applies is mood disorders due to another medical condition such as stroke with depressive features, major depressive-like episode, or mixed-mood features. It is often associated with large vessel infarction. (DSM-5 293.83; Robinson and Jorge, AJP, Volume 173, Issue 3, March 01, 2016, PP. 221-231).
- A patient who is a candidate for this diagnosis would present with depressed mood or loss of interest or pleasure along with four other symptoms of depression (e.g., weight loss, insomnia, psychomotor agitation, fatigue, feelings of worthlessness, diminished concentration, suicidal ideation) lasting two or more weeks.
- Several mechanisms, including biological, behavioural, and social factors, are involved in its pathogenesis.
- Symptoms usually occur within the first three months after stroke (early onset depression following stroke); however, may occur at any time (late onset depression following stroke). Symptoms resemble those of depression triggered by other causes, although there are some differences - people who have experienced a stroke with depression following stroke experience more sleep disturbances, vegetative symptoms, and social withdrawal.
Vascular depression is a newer concept incorporating a broader range of depressive disorders. Vascular depression is related to small-vessel ischemia and people experiencing vascular depression may have white matter disease seen on brain imaging. Vascular depression also includes post-stroke depression as a sub-category. People who have experienced a stroke with vascular depression have later age of onset, greater cognitive impairment, less family and personal history of depression, and greater physical impairment than geriatric persons with nonvascular depression. They have been found to have different responses to treatment and different prognoses. In addition, persons with vascular depression with executive dysfunction and/or persons who show progression of white matter hyperintensities over time have a poor response to treatment with antidepressants and a more chronic and relapsing clinical course (Taylor WD, Steffens DC, MacFall JR, et al: White matter hyperintensity progression and late-life depression outcomes. Arch Gen Psychiatry 2003; 60:1090–1096).
Apathy is most commonly defined as a multidimensional syndrome of diminished goal-directed behavior, emotion, and cognition (Sachdev 2017; Chen 2018). People present with loss of motivation, concern, interest, and emotional response, resulting in a loss of initiative, decreased interaction with their environment, and a reduced interest in social life. It can negatively impact recovery post-stroke. Apathy can occur as an independent syndrome, although it may also occur as a symptom of depression or dementia (Marin,1991; Starkstein 2008). Apathy has been reported to occur in 29 – 40% of people who have experienced a stroke (van Dalen 2013).
Anxiety following stroke is characterized by feelings of tension, extreme apprehension and worry, and physical manifestations, such as increased blood pressure. Anxiety disorders occur when symptoms become excessive or chronic. In the post-stroke literature, anxiety has been defined both by consideration of the presence and severity of symptoms using validated screening and assessment scales (such as the Hospital Anxiety and Depression Scale), or by defining syndromes using diagnostic criteria (e.g., panic disorders, general anxiety disorder, social phobia)
1.0 Post-Stroke Depression
All people who have experienced a stroke should be considered at risk for post-stroke depression, which can occur at any stage of recovery [Evidence Level A].
- People who have experienced a stroke and families should be given information and education about the potential impact of stroke on their mood [Evidence Level C].
- People who have experienced a stroke and families should be provided with the opportunity to talk about the impact of stroke on their lives at all stages of care [Evidence level C]. Refer to the CSBPR Transitions of Care Module for further information on Patient and Family Education, and Community Follow-up.
1.1 Screening for Post-Stroke Depression
- All people who have experienced a stroke should be screened for post-stroke depression if deemed medically appropriate, given the high prevalence of post-stroke depression and the evidence for treating symptomatic depression post stroke [Evidence Level B]. Note: ‘Medically appropriate’ excludes people who have experienced a stroke who are unresponsive or who have deficits that interfere with screening for mood disorders. Any pre-stroke mental health or cognitive diagnoses should be taken into consideration during the screening process.
- Screening should be undertaken by trained professionals using a validated screening tool to maximize detection of depression [Evidence Level B]. Refer to Appendix Two, Table 1A for a summary of suggested validated screening tools
- Stroke assessments should include evaluation of risk factors for depression, particularly a history of depression [Evidence Level C]. Refer to note below for list of risk factors.
- For people who experience some degree of communication challenge or deficits following stroke, appropriate strategies that do not rely on verbal communication should be implemented for screening of possible post-stroke depression to ensure adequate screening and assessment and access to appropriate treatment [Evidence Level C]. Refer to the CSBPR Stroke Rehabilitation Module for further information on communication deficits.
Note: Common risk factors associated with post-stroke depression include increasing stroke severity, functional dependence, presence of cognitive impairment, and history of previous depression. Increased functional dependence (e.g. requiring help with activities of daily living) and having a history of pre-stroke depression may be the two most salient risk factors for the development of post-stroke depression. Communication deficits and social isolation may also be considered as possible risk factors for depression. Refer to CSBPR Transitions of Care Module for information on depression in family and informal caregivers of people with stroke.
1.2 Assessment for Post-Stroke Depression
- People who have experienced a stroke whose screening indicates a high risk for depression should be assessed in a timely manner by a healthcare professional with expertise in diagnosis, management and follow-up of depression [Evidence Level C].
Clinical Considerations 1.2: Timing of Screening for Post-Stroke Depression (New in 2019)
- Screening for post-stroke depression may take place at various stages throughout the continuum of stroke care, especially at transition points, as time of onset for post-stroke depression can vary and include:
- At transfer from an inpatient acute setting to an inpatient rehabilitation setting;
- From an inpatient rehabilitation setting before return to the community;
- During secondary prevention clinic visits;
- Following discharge to the community, during follow-up appointments with consulting specialists, and during periodic health assessments with primary care practitioners.
- Screening for depressive symptoms could be considered during the initial acute care stay, if deemed medically appropriate, particularly if evidence of depression or mood changes is noted or if risk factors for depression are present, as outlined in section 1.1, iii.
- Repeated screening may be required since the ideal timing for screening for post-stroke depression is unclear.
1.3 Non-Pharmacological Management of Post-Stroke Depression
- It is reasonable to consider either cognitive-behavioural therapy or interpersonal therapy as one of the first line treatments for depressive symptoms post stroke [Evidence Level B], as a monotherapy.
- Treatment for post-stroke depression may include psychotherapy as an adjunct in combination with antidepressants [Evidence Level A], as appropriate to the person who has experienced a stroke’s health state and other deficits (e.g., communication and other cognitive deficits).
Clinical Considerations 1.3
- Other approaches to adjunctive treatment of post-stroke depression are emerging, with research in very early stages. These include music, mindfulness, and motivational interviewing. These therapies could be considered on an individual basis at the discretion of the treating healthcare professional in consultation with the person with stroke and their family if appropriate.
- Other therapies including deep breathing, meditation, visualization, physical exercise, repetitive transcranial magnetic stimulation, or, for severe refractory depression, electro-convulsive therapy or deep brain stimulation. These have all been suggested in the literature but lack sufficient evidence for routine use and require more research.
1.4 Pharmacotherapy for Post-Stroke Depression
- People who have experienced a stroke with mild depressive symptoms or those diagnosed with minor depression may initially be managed by “watchful waiting” * (Evidence Level B]. See note below for definition of watchful waiting.
- Pharmacological treatment should be considered and started if the depression is persistent or worsens and interferes with clinical goals [Evidence Level B].
- People diagnosed with a depressive disorder following stroke should be considered for a trial of antidepressant medication [Evidence Level A].
- No one drug or drug class has been found to be superior for post-stroke depression treatment. Side effect profiles, however, suggest that some selective serotonin reuptake inhibitors may be favoured in this patient population [Evidence Level A].
- Choice of an antidepressant medication will depend upon symptoms of depression, potential known side effects of the medication, particularly in the child or older adult, drug interactions with other current medications and underlying disease conditions. Refer to Appendix Two, Table 1C for a summary of the efficacy and safety of pharmacologic agents for the treatment of post-stroke depression.
- Response to treatment should be monitored regularly by a health professional. Monitoring should include evaluation of any changes in the severity of depression, review of potential side effects, and update of ongoing management plans [Evidence Level C].
- If a good response is achieved, treatment should be continued for a minimum of six to 12 months. [Evidence Level C].
Note: Examples of a ‘good response’ may be indicated by positive changes in thoughts and self-perceptions (e.g., hopelessness, worthlessness, guilt), emotional symptoms (e.g., sadness, tearfulness), neurovegetative symptoms (e.g., sleep, appetite), and improved motivation to carry out daily activities.
- If the person’s mood has not improved 2-4 weeks after initiating treatment, assess patient compliance with medication regime. If compliant, then consider increasing the dosage, adding an additional medication, or changing to another antidepressant [Evidence Level B].
- Following the initial course of treatment, maintenance therapy could be considered on an individual basis (consider previous history and risk factors for recurrence of depression). [Evidence Level C].
- If a decision is made to discontinue an antidepressant, it should be tapered over one to two months [Evidence level C].
- Following initial treatment for post-stroke depression, people who have experienced a stroke should continue to be monitored for relapse or recurrence of depression [Evidence Level C].
- Pseudobulbar Affect: In cases of severe, persistent or troublesome tearfulness, emotional incontinence or lability, a trial of antidepressant medication should be considered [Evidence Level A].
- Side effect profiles suggest that some selective serotonin reuptake inhibitors may be preferred over others for this population. There is no evidence for non-pharmacologic interventions for this condition. Refer to Appendix Two, Table 1C for a summary of suggested pharmacotherapy agents for the treatment of post-stroke depression.
Note: Watchful waiting is defined as a period when the person who experienced a stroke displays mild depressive symptoms is monitored closely without additional therapeutic interventions to determine whether the mild depressive symptoms will improve. The timeframe for watchful waiting varies in the literature, typically between 2-4 weeks. It is often described as including suggestions for self-help strategies and participation in physical exercise.
- The involvement and feedback of people who have experienced a stroke, their family and caregivers is an important component of ongoing monitoring for post-stroke mood changes and conditions.
- Counselling and education should include information about potential relapse or recurrence of symptoms, signs to be aware of, the importance of adherence with prescribed medication regime, and contacting their primary care physician or mental health expert should those signs reappear.
1.5 Prophylactic Treatment for Post-Stroke Depression
- While prophylactic pharmacotherapy has been shown to prevent post-stroke depressive symptoms [Evidence Level A], their impact on function is less clear. At this time routine use of prophylactic antidepressants for ALL people who have experienced a stroke is not recommended as the risk–benefit ratio has not been clearly established [Evidence Level B].
- Further research is required to define at risk people who have experienced a stroke, choice of antidepressant agents, optimal timing and duration of intervention.
- Problem-solving therapy (i.e., cognitive-behaviour therapy) has been shown to have efficacy for prophylactic treatment for post-stroke depression [Evidence-Level B].
1.6 Other Mood States
- Screening for anxiety may be considered in people who have experienced a stroke as increased prevalence has been demonstrated following stroke [Evidence Level B].
- A validated screening tool should be used to detect presence of anxiety [Evidence Level B].
- People who have had a stroke with resulting communication limitations should be screened for anxiety using appropriate methods validated for aphasic people who have experienced a stroke [Evidence Level B].
- Anxiety frequently co-exists with depression following stroke or may appear in people who have experienced a stroke who are not clinically depressed. For people who have experienced a stroke with marked anxiety with or without clinical depression, it is reasonable to offer pharmacotherapy [Evidence level C].
- Although evidence is limited in people who have experienced a stroke, psychotherapy may be considered as an adjunct to pharmacotherapy [Evidence Level C].
- Problem-solving therapy (i.e., cognitive behaviour therapy) has been shown to have efficacy for anxiety post-stroke [Evidence Level B].
- Apathy frequently co-exists with depression following stroke or may appear in people who have experienced a stroke who and not clinically depressed. For people who have experienced a stroke with marked apathy, with or without clinical depression, it is reasonable to offer nonpharmacological intervention such as exercise or music therapy [Evidence Level C]. Psychostimulants have been trialed, but evidence remains limited [Evidence Level C].
1.7 Ongoing Monitoring, Support and Education
- People who have experienced a stroke and families should continue to be given information and education about the potential impact of stroke on mood [Evidence level C].
- People who have experienced a stroke and families should be provided with the opportunity to talk about the impact of stroke on their lives at all stages of care Refer to the CSBPR Transitions of Care Module for further information on Patient and Family Education, and Community Follow-up.
Approximately one-third of all individuals who experience stroke will exhibit symptoms of depression at some time following the stroke event (acute, sub-acute and at long-term follow-up). A substantially increased prevalence of depression following stroke has been reported in up to 24% of people who have experienced a stroke (24% vs 8% compared to general population). Many studies report the highest incidence of post-stroke depression may present within the first three to six months following stroke, and other studies with longer follow-up have reported new onset of post-stroke depression emerging up to two years after index stroke. In one study, post-stroke depression also was reported in 48% of 71 young people who have experienced a stroke after at least one year of follow-up. Post-stroke depression may prove to be persistent for as many as one-half of the individuals identified as depressed soon after stroke. Severity of functional limitations, stroke severity, cognitive impairment, age of stroke onset, and a previous history of depression have all been identified as important risk factors for the development of post-stroke depression.
Post-stroke depression is associated with poorer functional recovery, increased risk for dependence, poorer cognitive function and reduction in social participation. In addition, the presence of post-stroke depression has been associated with increased risk for mortality. Appropriate identification, diagnosis and treatment of post-stroke depression have been associated with improved outcomes.
Families and caregivers of people who have experienced a stroke are also at risk for depression, with the reported incidence as high as 30% to 60% of caregivers experiencing depressive symptoms.
Anxiety and apathy have been reported in 20-30% of people who have experienced stroke, either alone or in combination with a diagnosis of post-stroke depression.
The findings of this review lead to several implications for the healthcare system as follows:
- Education for primary care practitioners and healthcare providers across the continuum of stroke care on recognition, assessment, and management of post-stroke depression.
- Screening tools should be available that are sensitive to unique circumstances, such as people who have experienced a stroke with communication or cognitive deficits and tools that may be culturally appropriate.
- Timely access to appropriate mental health specialists as needed who are able to diagnose and evaluate severity of depression and provide guidance for ongoing management.
- Timely access to and availability of specialized therapies to manage post-stroke depression, including counseling and psychotherapy as required.
- The development and implementation of an equitable and universal pharmacare program, implemented in partnership with the provinces, designed to improve access to cost-effective medicines for all people in Canada regardless of geography, age, or ability to pay. This program should include a robust common formulary for which the public payer is the first payer.
- Mechanisms to ensure good communication and information flow between the range of specialists and programs beyond the core stroke care providers to meet the varied needs of individuals post stroke (e.g., mental health specialists, cognitive specialists, geriatric programs).
- Process for ongoing monitoring of any person who experienced a stroke with positive screening for depression during screening and assessment process.
- Education and support for caregivers of people who have had a stroke.
- Processes should be in place to provide education and ensure that the caregivers’ emotional needs are monitored and addressed, ideally through involvement of the primary health care team.
- Optimization of strategies to prevent the recurrence of stroke.
- Proportion of people with acute stroke with documentation indicating initial screening for post-stroke depression was performed (either informally or using a formal screening tool) in the acute care, rehabilitation, long-term care and community settings (e.g., homecare) setting. (Core Indicator)
- Proportion of people with acute stroke referred for additional assessment or intervention for a suspected diagnosis of depression.
- Proportion of people who have experienced a stroke diagnosed with post-stroke depression who are treated with antidepressants and/or psychotherapy at appropriate time points following the initial stroke event, such as at 30, 60, and 90 days, six months, and one year.
- Recommendations for screening and assessment of post-stroke depression and corresponding performance measures apply across the continuum of stroke care and should be considered in the acute, early rehabilitation, and longer-term recovery in the community, and apply across all healthcare settings.
- When monitoring these performance measures, it is important to record when and in what context (continuum of care) the measurements were conducted, as well as the specific tools used for measurement.
- Data for measurement may be found through primary chart audit. Data quality will be dependent on the quality of documentation by healthcare professionals.
- For people who have experienced a stroke referred to psychiatry, information may be available through provincial physician billing databases; some privacy regulations may limit access to certain data.
- For persons over 65 years old, information on medication prescriptions may be available through provincial and territorial senior drug benefit plan databases.
- For performance measure 3, the intent is to increase the number of people with post-stroke depression who are adequately treated and reduce the number of people who have experienced a stroke with depression who are untreated (depressive disorder + no antidepressant medication) and undertreated (depressive symptoms + antidepressant medication + ongoing symptoms). This should be considered in the measurement and analysis plan.
Health Care Provider Information
- Table 1A: Selected Validated Screening and Assessment Tools for Post-Stroke Depression
- Table 1B: Selected Validated Screening and Assessment Tools for Post-Stroke Anxiety
- Table 1C: Summary Table for Selected Pharmacotherapy for Post-Stroke Depression
- Evidence-based Review of Post-Stroke Depression (EBRSR)
- StrokEngine, Depression section
- NHS Psychological care after stroke
- APA Diagnostic and Statistical Manual of Mental Disorders (DSM)
- Taking Charge of Your Stroke Recovery
- Your Stroke Journey
- Stroke Care Tips and Tools - A Guide for Stroke Caregivers
- Recognizing and Handling Stress
- Post-Stroke Checklist
- Depression, Energy, Thinking and Perception
- Recovery and Relationships
- Support for family members and caregivers
Post-Stroke Depression and Mood Evidence Tables and Reference List
- Evidence Table 1A Post stroke Depression Screening and Assessment
- Evidence Table 1B Non-pharmacological Interventions
- Evidence Table 1C Pharmacotherapy and Combined Treatment
Post-stroke depression (PSD) is a common consequence of stroke, although reported estimates may be unreliable given possible under-reporting of unusual mood, and the variability in the methods used to assess and define cases of depression within the literature. In a systematic review of 61 prospective, observational studies of post-stroke depression conducted in hospital-, rehabilitation-, and population-based settings, Hackett & Pickles (2014) estimated that approximately one-third of all individuals who experience stroke exhibited depressive symptoms at some point following the event (i.e., at acute, sub-acute or long-term follow-up). The overall pooled frequency estimate of PSD was 31% (95% CI 28% to 35%). Salinas et al. (2017) reported that of 1,424 postmenopausal women included in the Women’s Health Initiative who experienced a first-ever stroke, new-onset PSD occurred in 21.4% of participants, at an average of 16 months post stroke. Jorgensen et al. (2016) reported the incidence of persons developing depression was significantly higher compared with those of the general population matched for age and sex. During a two-year observation period, the incidence of depression was 25.4% vs. 7.8% (adj HR=4.09, 95% CI 4.00-4.18). In the prospective Depression Predictors after Ischemic Stroke study (DEPRESS), Guiraud et al. (2016) reported that among 251 patients with new onset stroke, the incidence of depression was 19% at two months and 24.3% at six months. Risk factors for the development of PSD include increasing age, living alone, high levels of comorbidity, a history of depression, female gender, physical disability (mRS score >2 at discharge), increased initial stroke severity, cognitive impairment and prior history of stroke. (Guiraud et al. 2016, Jorgensen et al. 2016, Kutlubaev & Hackett 2014, Ayerbe et al. 2013b).
The best time to screen formally for the possible presence of PSD is not certain. Although incident rates decline over time and there is a general trend toward improvement in depressive symptomatology during the first-year post stroke, PSD may prove to be persistent for a longer duration for a significant proportion of individuals. Screening for depression should be considered during the acute inpatient stay, at the point of transition to, or during inpatient rehabilitation, upon discharge to the community and during periodic health assessments. Swartz et al. (2017) describes the feasibility of using the 2-item version of the Patient Health Questionnaire during routine clinical practice using 1,500 outpatients attending a stroke prevention clinic. All patients were able to complete the screen, 89% of whom did so in less than 5 minutes. Karamchandani et al. (2015) reported that 70% of patients were eligible for depression screening prior to hospital discharge or transfer to another service. The remaining patients were not eligible due to aphasia, other medical condition, hospice/comfort measures, or prolonged intubation.
The diagnostic accuracies of several post-stroke depression screening and assessment tools have been examined. Meader et al. (2014) included the results of 24 studies and evaluated the performance of 18 previously-validated scales. The three best performing scales for the identification of any depression included Center of Epidemiological Studies-Depression Scale (CES-D) with a sensitivity and specificity of 75% and 85%, the Hamilton Depression Rating Scale (HDRS, sensitivity 84%, specificity 83%) and the 9-item version of the Patient Health Questionnaire (PHQ-9, sensitivity 86%, specificity 79%). The best two performing scales for the identification of major depression were HDRS and the PHQ-9. In a Canadian study (Prisnie et al. 2016) including 122 outpatients attending a stroke prevention clinic, the diagnostic accuracies of the PHQ-9 and PHQ-2 were evaluated. Using a cut-point of 13, the sensitivity and specificity of the PHQ-9 was 81.8% and 97.1%, and 75.0% and 96.3%, for PHQ-2, using a cut point of three.
Once possible depression has been detected via formal screening using a validated screening tool and the diagnosis confirmed by an experienced healthcare professional, treatments may be initiated. Pharmacotherapy with antidepressants has been associated with a reduction of depressive symptomatology. Xu et al. (2016) included the results from 11 RCTs of patients with a clinical diagnosis of post-stroke depression. Treatment with an antidepressant was associated with a significant reduction in depression scores (SMD=-0.96, 95% CI -1.41 to -0.51, p<0.0001), and better response to treatment (RR=1.36, 95% CI 1.01-1.83, p=0.04). A Cochrane review authored by Hackett et al. (2008), also reported the odds of remission of depression (i.e. a reduction of ≥50% in depression scale scores) were significantly higher with pharmacotherapy. Most of the agents evaluated in these reviews were selective serotonin reuptake inhibitors and tricyclic antidepressants. A systematic review by Chen et al. (2006) identified a relationship between duration and benefit of treatment. Analysis of studies with treatment durations of one and two weeks revealed no significant treatment effects; however, when treatment lasted for three weeks or more, the effects were greater. Many adverse events were associated with the use of pharmacotherapy in these studies.
Antidepressants have also been shown to improve functional recovery and reduce dependency in a person post stroke, both with, and without post-stroke depression (Mead et al. 2012, Chollet et al. 2011). The use of antidepressants has also been associated with reductions in emotional lability (Hackett et al. 2010), a common consequence of stroke. Pooling the results from 3 trials, the odds of improvement (i.e., reduction) in tearfulness were significantly increased in the treatment group (OR=9.35, 95% CI 4.26 – 20.54).
Non-pharmacological approaches to the treatment of post-stroke depression include different forms of psychotherapy, physical activity, non-invasive brain stimulation, and acupuncture. Psychotherapy (including problem solving therapy, cognitive behavioural therapy and motivational interviewing), has not been shown to be an effective treatment for depression in person recovering from stroke when used in isolation (Hackett et al. 2008), however, these same techniques may be effective when used in combination with pharmacotherapy (Mitchell et al. 2009). Behavioral therapy was shown to be effective for the treatment of post-stroke depression in persons with aphasia (Thomas et al. 2012). Acupuncture was shown to be superior to pharmacotherapy in the treatment of post-stroke depression. In a meta-analysis including the results of 15 RCTs of persons with post-stroke depression (Zhang et al. 2012), treatment with acupuncture was associated with improved odds of recovery/remission compared with pharmacotherapy (OR=1.48, 95% CI 1.10-1.97). Non-invasive brain stimulation using either repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been shown to improve symptoms of depression. Significant reductions in Hamilton Rating Scale for Depression (HAD-D) scores were reported following two to eight weeks of rTMS therapy, compared with sham treatment in a meta-analysis including the results from 22 RCTs (Shen et al. 2017). At the end of treatment, the mean reduction in HAM-D scores was significantly greater for the rTMS group (MD=-6.09, 95% CI -7.74 to -4.45, p<0.0001). The ability of persons to perform ADLs was also significantly greater in the rTMS group (SMD=1.20; 95% CI 0.68-1.72, p<0.001). Treatment with 12, 30-minute sessions of tDCS (2 mA) in persons with post-stroke depression, treated an average of 15 months post stroke has also been associated with significant reductions in HAD-D scores (Valiengo et al. 2017). Physical activity has been associated with a small, but significant reduction in depression scores in a meta-analysis authored by Eng & Reime (2014) including the results from 13 RCTs (SMD=−0.13, 95% CI −0.26 to −0.01, p=0.03).
Prevention of Post-Stroke Depression
Given the high prevalence of post-stroke depression and the negative consequences associated with it, there has been increasing attention paid to strategies for its prevention. Pharmacologic prophylaxis, using many of the same agents, used for treatment, has been most commonly evaluated. In a pooled analysis based on 776 observations from 12 RCTs, Salter et al. (2012) reported the odds of developing post-stroke depression were reduced significantly with the use of prophylactic pharmacotherapy (OR=0.34, 95% 0.22-0.53, p<0.001). Similar effects have been reported in other systematic reviews (Yi et al. 2010, Chen et al. 2007). Non-pharmacological approaches have also been evaluated for the prevention of post-stroke depression. A Cochrane review (Hackett et al. 2008) included four trials that evaluated psychotherapeutic interventions, including problem-solving therapy (PST), home-based therapy and motivational interviewing. The odds of developing depression were significantly lower for participants in the active intervention groups (OR= 0.64, 95% CI 0.42 to 0.98, p=0.04), while psychological interventions were associated with a significant improvement in General Health Questionnaire (GHQ)-28 scores from baseline to end of treatment (MD= -1.37, 95% CI -2.33, -0.40, p=0.006). In a trial that included pharmacological and non-pharmacological study arms with long-term follow-up, Robinson et al. (2008) randomized 176 patients without depression to receive escitalopram, problem-solving or placebo, which was provided for 12 months. At one year, in the per-protocol analysis, adjusted for previous history of mood disorders, patients assigned to the placebo condition were significantly more likely to develop depression compared with those receiving either therapy with escitalopram (adj. HR= 4.5, 95% CI 2.4-8.2, p<0.001) or problem-solving therapy (adj. HR=2.2, 95% CI 1.4-3.5, p<0.001). In a follow-up study, Mikami et al. (2011) reported that when escitalopram was discontinued at the end of the study period, persons were more likely to develop major depression and had increased Hamilton Depression Rating Scale HDRS scores during the next six months, compared with those given placebo or PST. Finally, after a mean duration of eight years of follow-up, Robinson et al. (2017) reported that participants who received PST were significantly less likely to have died, compared with the combined group of escitalopram + placebo. Increasing age and the development of depression were found to be significant predictors or mortality.
Treatment of Anxiety Following Stroke
People with depression may also have a comorbid generalized anxiety disorder (GAD). Anxiety following stroke occurs in 20-25% of patients and is more common in women (Campbell et al. 2013). Despite the prevalence of post-stroke anxiety, very few studies have included evaluation of the effectiveness of potential treatments. A Cochrane review (Knapp et al. 2017) identified only three RCTs examining pharmacotherapy (paroxetine, buspirone) and a self-help autogenic relaxation CD). While the results from individual trials were positive, the results could not be pooled. The authors concluded there was insufficient evidence to guide treatment. Non-pharmacological approaches to the treatment of anxiety that have been reported to reduce anxiety symptoms include a self-help program (Golding et al. 2016 a,b), multidisciplinary in-home visits from rehabilitation therapists (Ryan et al. 2006) and acupuncture (Ping & Songhai 2008).