Treatment options for post-stroke depression in the ... - Future Medicine

7 downloads 48 Views 306KB Size Report
Health, Royal Prince Alfred. Hospital and The University of Sydney, PO ...... Rothwell PM, Coull AJ, Giles MF et al.: Change in stroke incidence, mortality, case-.
R EVIEW

For reprint orders, please contact: [email protected]

Treatment options for post-stroke depression in the elderly Maree L Hackett & Craig S Anderson† †Author

for correspondence

Neurological Diseases and Aging Division, The George Institute for International Health, Royal Prince Alfred Hospital and The University of Sydney, PO Box M201, Missenden Road, Sydney, NSW 2050, Australia Tel.: +61 2 9993 4500; Fax: +61 2 9993 4502; E-mail: canderson@ thegeorgeinstitute.org

Keywords: aging, cerebrovascular disease, depression, evidence, healthcare, stroke

Depression is an important complication of stroke – although common and associated with poor outcomes it is often undetected, undiagnosed, untreated or undertreated. There are several explanations for this unsatisfactory situation: it undoubtedly reflects complexities in the assessment of mood disorders in patients with disability and medical comorbidities; there are various barriers to implementation of effective antidepressant therapy in clinical practice; and there is a lack of high-quality, randomized evidence of effective management strategies in this aspect of stroke care. As well as education of healthcare providers and the general public on the importance of depression in the context of physical illness, new models of multidisciplinary healthcare delivery on stroke outcomes and cost-effectiveness need to be explored in different settings. There is a need for research to investigate etiologic factors and produce randomized evaluations of interventions for the prevention and treatment of post-stroke depression.

As a leading cause of death and adult disability, stroke is a major healthcare problem of increasing global importance. Currently, an estimated 17 million people experience a ‘first-ever’ stroke around the world each year, and of the approximately 11 million people who survive the acute illness, at least a third will remain dependent on others either for direct personal care or supervision in their everyday activities [1]. Given that most (∼75%) strokes occur in people over the age of 65 years, rates are expected to rise in both developed and developing countries as populations undergo aging and other structural and lifestyle changes [2]. Moreover, the burden of care is likely to shift from hospitals to the community because of economic pressures and as the prevalence of people living with the effects of stroke increases due to declines in ‘severe’ strokes and/or improvements in survival [2]. The often dramatic clinical expression and physical consequences of stroke are well known and strongly influence how acute healthcare and rehabilitation services are configured both in size and scope. However, the fact that stroke is also an important cause of neuropsychiatric and behavioral disturbance is less well appreciated and consequently managed in clinical practice [3]. This review provides an overview of the frequency and management of depression following stroke. Some of the authors’ own work will be drawn upon in systematically reviewing this literature and special attention is given to the disorder in older patients. Some of the complexities in recognizing and assessing depression will

10.2217/1745509X.1.1.95 © 2005 Future Medicine Ltd ISSN 1745-509X

also be addressed and, where direct evidence is lacking, recommendations for clinical practice and research are made on the basis of the wider literature pertaining to the management of depression in older people. Depression in later life Depression is one of the leading causes of disability worldwide [4]. While the term ‘depression’ can be used to describe varying mood states that range from a mild lowering in mood, energy and activity, to that of a life-threatening psychiatric illness, in a typical depressive episode, enjoyment, concentration, self-esteem and self-confidence are reduced together with disturbances of sleep, appetite and other physical effects. Such depressive symptoms are judged to be clinically significant when they interfere with normal activities and persist (arbitrarily) for 2 weeks or more [5]. The spectrum, severity and duration of particular symptoms determine whether a depressive episode is classified as a mild-to-moderate (dysthymia) or a severe (major) form of depressed mood or diagnosable depression [6]. Such a classification helps to prioritize treatment and programs of care, as well as being necessary for scientific and regulatory purposes. Major and minor depression affect up to 10% of older adults in the general population [7], but are even more prevalent in long-term institutional care settings. Depression is more often a chronic and relapsing disorder rather than an illness with discrete episodes [8]. If untreated, a ‘major’ depressive episode typically lasts at least Aging Health (2005) 1(1), 95-105

95

REVIEW – Hackett & Anderson

several months [9] and is associated with substantial suffering, functional impairment and diminished health-related quality of life [10]. As well as being the most common mental disorder leading to suicide [6], major depression is associated with physical inactivity, misuse of alcohol and other drugs [11], and an increased risk of comorbid mental problems such as anxiety, panic and obsessive–compulsive disorders [12]. Moreover, depression complicates the management of medical conditions, adversely affecting recovery and rehabilitation, and reducing adherence to medication and treatment, and the ability of the patient to care for themself [13]. These effects lead, directly or indirectly, to higher complication rates, longer periods of healthcare, higher health and social costs, and an increased risk of vascular-related events and death [14,15]. There are now a variety of treatment options for depression in older people, together with emerging treatment guidelines [16], and most of the treatment takes place in primary care. Even so, mood disorders in late life are under-diagnosed in general, with depression being missed in approximately half of all older people with a mood disorder [17,18]. Yet efforts to improve treatment through the implementation of screening, healthcare practitioner feedback and other activities have produced inconsistent improvements in care [19]. Despite older people being more likely to be physically ill or bereaved [20], depression should not be considered a natural consequence of aging. Frequency of depression after stroke A variety of psychologic and behavioral disturbances have been described in association with stroke. In most instances, these disturbances include some form of depression that is of mildto-moderate severity. Studies suggest that depression following stroke may impede rehabilitation [21] by impairing physical and cognitive function [22,23], and contribute to stress on caregivers [24]. Furthermore, ‘post-stroke depression’ may also be associated with an increased risk of death [25,26], including suicide [27]. A wide range of frequencies of post-stroke depression have been reported in the literature, reflecting differences in case-mix and methods of assessing depression across studies. However, it is generally considered that the disorder occurs in at least a quarter of patients in the first year after stroke [28,29], with the period of greatest risk being within the first few months after onset [30,31]. 96

In order to better quantify the burden of depressive illness following stroke, the authors have recently completed a systematic review of all high quality, epidemiologic studies with prospective, consecutive recruitment of patients [32]. Data were available from 51 studies (reported in 96 publications) conducted between 1977 and 2002. Pooled estimates indicate that, on average, one in three survivors experience depression at some time after stroke onset. Moreover, the consistent proportional frequencies across varying stages of patient follow-up in studies suggest similar early and late risks of depression after stroke. This review also highlighted the limited use of interventions (either antidepressants or psychotherapy) for depression, although less than half of the included studies collected or reported data on antidepressant use. It would appear, therefore, that many stroke patients do not receive treatment for depression, with a passive attitude of many doctors to such therapy being highlighted by others [33]. This invariably reflects problems with diagnosis, but it may also reflect uncertainty among clinicians about the balance of benefits and risks (including side effects) of pharmacologic-based therapies in this setting. Despite advances in healthcare and a better awareness of the importance of mental health in overall wellbeing, there remains a common perception that depression is an understandable part of the natural process of adjustment to associated loss of function and resulting alterations in lifestyle and relationships that may occur after stroke. The vascular depression hypothesis in old age Vascular depression is a term that is increasingly being used to describe depression in the context of advanced age, cognitive impairment and silent strokes, and is supported by the high frequency of depression in association with vascular risk factors such as hypertension, diabetes and coronary artery disease [34]. The hypothesis argues that ‘small vessel’ cerebrovascular disease, particularly where there is disruption of the frontal-subcortical regions of the brain, places older people at increased risk of depression [35]. How great this association is over and above the effects of general comorbid medical conditions and physical disability is uncertain [36], although the direct effects of vascular disease may be particularly important in the very elderly [37]. Aging Health (2005) 1(1)

Treatment options for post-stroke depression in the elderly – REVIEW

The importance of the location of stroke lesion in the left anterior hemisphere, first postulated in 1975 [38], is probably the most commonly cited explanation for post-stroke depression. However, three recent systematic reviews on the association between lesion location and depression call into question the importance of such a biologic explanation [39–41]. Although these reviews covered 53 studies, 13 publications were authored by one group, in which only two distinct cohorts could be readily identified [42,43]. Despite these reviews varying in several ways (for example, different inclusion/exclusion criteria and varying degrees of completeness of search strategies), two found no evidence to support the lesion location theory [39,40], while the other found some evidence of an association of depression with lesion location (hospital-based patients were more likely to experience depression if they had a lesion in the left hemisphere, whereas population-based patients were more likely to experience depression if they had a lesion in the right hemisphere) [41]. However, this latter review did not remove the aforementioned duplicate publications, which leads to the conclusion that the evidence to support an association between the development of depressive symptoms and lesion location is weak. The authors’ own systematic review was designed to determine whether there are simple clinical variables that might predict the development of depression following stroke. The data show a wide variation in the selection and significance of potential variables, and in the quality of the statistical modeling across the individual studies. Only stroke severity, physical disability and cognitive impairment were consistently identified as being positively associated with depression following stroke. Detection of depressive disorders following stroke Few health professionals have difficulty diagnosing depression in young, otherwise healthy, people whose predominant complaints are of feeling sadness, hopelessness and depression with evidence of insomnia and loss of appetite. However, in stroke patients, the confounding influence of cognitive, sensory and language impairment and other factors add complexities to the assessment of mood. As such, there is little agreement among clinicians and researchers regarding the appropriate way to determine the presence of mood disorders in this patient group [44]. www.futuremedicine.com

In part, difficulties with the diagnosis of depression lie in the tools available for assessment and categorization of symptoms. The gold standard method of diagnosis in the clinical setting is the semi-structured psychiatric interview, which results in a diagnosis meeting certain standard (for example, Diagnostic and Statistical Manual of Mental Disorders [DSM] or Internation Classification of Diseases) criteria. The DSM diagnostic criteria for a depressive disorder include retardation, fatigue, and sleep and appetite disturbances [45], all of which may be a consequence of the stroke itself and independent of mood [46]. Disturbances of behavior, facial expression, and verbal communication resulting from stroke, may mask or mimic symptoms of depression. In addition, the DSM diagnostic criteria require modification for use in stroke patients, removing the need for symptoms of dysthymia, or mild depression, to be present for at least 2 years, and overlooking the presence of the concurrent medical condition of stroke. While DSM-IV criteria do provide a reliable diagnosis of major depression in patients with stroke [47,48], most clinicians involved in the care of such patients are not familiar with this approach, and psychiatric expertise is not readily available in all health systems. Moreover, semistructured psychiatric interviews are not only time consuming but are heavily weighted toward verbal responses, making the assessment of dysphasic patients particularly difficult, if not impossible. Mood scales, or questionnaires, are the preferred method of assessing depressive symptom burden in routine clinical care. While many standardized depression scales have been used, there are a variety of concerns with the use of selfand interviewer-administered scales in this patient group. The first, and probably most obvious, concerns the stroke patients’ ability to complete the scales, given the possibility of dysphasia, impaired writing ability and vision disturbances [49]. In these instances, an interviewer may administer a scale to guide their assessment of the patient’s responses, and visual cues such as the use of ‘sad’ or ‘happy’ faces, or visual-analog scales, may be helpful. Self- and interviewer-administered scales have been shown to yield very similar results in detecting cases in epidemiologic studies, despite respondents being likely to provide more socially acceptable answers with an interviewer [50]. Management of post-stroke depression The main aims of treatment are to reduce depressive symptoms, improve mood and quality of life, reduce the risk of medical complications 97

REVIEW – Hackett & Anderson

including relapse, and facilitate the appropriate use of healthcare resources [5,51]. The optimal outcome of treatment is full remission, and staying well in the long term. Although there is no universal definition of ‘remission’, in clinical practice it is generally considered to be minimal or no symptoms of depression and a return to normal functioning. The management of depressive disorders requires consideration of medication (or pharmacotherapy), psychotherapy [6], and electroconvulsive therapy (ECT) in those with severe depressive illness [52]. Special attention is required to overcome the many barriers to obtaining and adhering to treatment for depression. All treatment should be tailored to individual needs, taking into consideration the severity and duration of the disorder, and patient preferences including cost, accessibility and availability. Effective treatment will generally include the involvement of spouses or partners, family, and other support networks. In all circumstances, it is recommended that the treating clinician monitor a person presenting with depression at least weekly for the first 6 weeks to assess mood, suicidal thinking, physical safety, the person’s social situation and side effects of any drugs that have been prescribed. Education about the depressive disorder should also be provided, in short sessions, and some lifestyle changes may be recommended including stress management, reducing drug and alcohol use, improving sleep patterns, having a balanced diet and partaking in physical exercise [53]. Pharmacotherapy

Antidepressants are an effective treatment for most moderate and severe depressive disorders, but are generally not indicated for mild disorders because the balance of benefit and risk is poor [52]. Antidepressant treatment is intended to reduce or control depressive symptoms, and to prevent relapse [6]. While newer classes of selective serotonin reuptake inhibitors (SSRIs) may have fewer side effects compared with older tricyclic antidepressants, current data do not support the efficacy of one antidepressant agent over another [6,9]. However, side effects have become a central consideration in depression treatment, and consideration must be given to what is tolerable, in exchange for the medication’s intended effect [54]. Unfortunately, antidepressant treatment is often prescribed at inadequate doses and for shorter durations than recommended [5]. In addition, approximately 30% of patients do not respond to the first drug they are prescribed [54]. 98

Individual trials suggest a benefit of antidepressants, not only in terms of remission of abnormal mood, but also in terms of cognitive impairment [54], and possibly also improved long-term survival [54]. However, the case selection and small sample size associated with many of these studies limits the external validity of the data. The authors aimed to assess the totality of the randomized evidence by conducting two systematic reviews, using Cochrane Review methodology, of randomized controlled trials of pharmacologic agents used either selectively for treatment, or more generally for prevention, of depression following stroke [58,59]. Seven treatment trials with 615 patients at entry, and nine prevention trials with 479 patients at entry were identified (Figures 1 & 2). Further details are presented in the Cochrane Library version of these reviews [58,59]. Most trials included patients (mean age range: 56–73 years) recruited within 1 month of stroke onset; however, the time from stroke onset to entry into a trial ranged from ‘within a few days’ to 195 days. Most trials excluded patients with communication or cognitive difficulties, or other co-existing conditions, that would interfere with the assessments or adherence to the treatment; other common exclusion criteria were a history of depression or recent or current use of antidepressant medication, and concurrent psychiatric disorders or deterioration. Seven trials used an SSRI, two used a serotonin antagonist and reuptake inhibitor, and other agents with antidepressant effects were used in the remaining trials. Treatment duration was generally short, but ranged from 2 weeks to 12 months. In this review, the authors were unable to show that pharmacotherapy was effective either in producing a remission, or in preventing the onset of, ‘diagnosable’ depressive illness in stroke patients (Figure 1). However, there was some evidence of a reduction (improvement) in mood scores as defined by the rating scales used in the treatment studies, but not in the prevention trials (Figure 2). A major challenge in undertaking this review, however, was in addressing the considerable methodologic heterogeneity both across and within studies, including variation in patient characteristics, methods of diagnosis and assessment of depression, multiple endpoints, and the frequent absence of a clearly defined a priori measurable primary outcome. While there was no evidence of harm associated with antidepressant treatment as evidenced by the reporting of adverse events, such adverse event data were seldom collected or reported adequately. Aging Health (2005) 1(1)

Treatment options for post-stroke depression in the elderly – REVIEW

Figure 1. Comparison of antidepressant versus placebo for the management of depression after stroke: meeting study criteria for depression at the end of treatment.

Study Treatment trials Clinician impression Ohtomo 1991 DSM-III Lipsey 1984 HDRS Anderson 1994 Fruehwald 2003 MADRS Murray 2002 Overall effect Prevention trials CGI Rasmussen 2003 Clinical impression Roh 1996 DSM-III-R Palomaki 1999 Robinson 2000a Robinson 2000b Overall effect

Treatment n/N

Control n/N

Peto OR (95% CI)

52/108

32/65

0.96 (0.52–1.77)

5/11

8/15

0.73 (0.15–3.47)

6/18 8/26

17/20 6/24

0.09 (0.02–0.42) 1.33 (0.38–4.63)

31/62

34/61

0.79 (0.39–1.61)

225

185

0.76 (0.51–1.12)

13/70

20/67

0.51 (0.24–1.19)

10/30

23/30

0.15 (0.05–0.47)

5/51 3/17 1/15

5/49 3/8 2/8

0.96 (0.26–3.53) 0.36 (0.05–2.38) 0.21 (0.02–2.84)

183

162

0.41 (0.24–0.7)

0.1

0.2

0.5

Favors treatment

1.0

2.0

5.0

Favors control

Note that this meta-analysis should be interpreted cautiously in view of the small sample sizes, small number of trials reporting this end point and the multiple methods used within and between trials to assess depression. Test for heterogeneity: p = 0.07 (treatment trials); p = 0.26 (prevention trials). Effect sizes are odds ratios (OR); error bars represent the 95% confident interval (CI). Reproduced with kind permission from Hackett et al.: Stroke 36,1092–1097 (2005). CGI: Clinical Global Impression of Depression, DSM; Diagnostic and Statistical Manual of Mental Disorders; HDRS: Hamilton Depression Rating Scale; MADRS: Montgomery Asberg Depression Rating Scale.

Although antidepressant treatment may, on average, be more effective than placebo in reducing depressive symptoms in stroke patients, the clinical significance of such modest changes in mood scores is uncertain. It is also important to note that up to half of all potentially eligible stroke patients were excluded from these trials due to communication problems, cognitive loss or previous psychiatric illness. Also, given that a key requirement of treatment is for patients to achieve a therapeutic dose of medication for an adequate period of time, treatments in most studies may have been provided for an inadequate duration. Although direct evidence of the benefits of antidepressants in stroke patients is unavailable, evidence exists in other clinical situations. As www.futuremedicine.com

most physicians would consider it unethical to deny treatment in a stroke patient with an overt major depressive episode, it is recommended that antidepressants be offered to those with moderate-to-severe depression, before psychologic interventions, and be continued for at least 4–6 weeks in the first instance, at the dose recommended by the manufacturer. If response to treatment after this time is unsatisfactory, the clinician should first determine whether the patient followed the treatment plan. If there is no improvement or reduction of symptoms, another antidepressant should be selected, or psychotherapy may be added. Once an effective antidepressant and dose is identified, treatment should continue for approximately 9–12 months in the first 99

REVIEW – Hackett & Anderson

Figure 2. Comparison of antidepressant versus placebo for the management of depression after stroke: average change in mood scores between baseline and end of treatment.

Study Treatment trials BDI Fruehwald 2003 CGI Fruehwald 2003 HDRS Lipsey 1984 Anderson 1994 Fruehwald 2003 MADRS Wart 2000 Murray 2002

Difference in mean score (95% CI)

Control N, Mean (SD)

Treatment N, Mean (SD)

26, -6.1 (5.60)

24, -4.1 (6.48)

-2.0 (-5.4–1.4)

26, -2.7 (1.16)

24, -2.1 (1.36)

0.6 (-1.3–0.1)

11, -11.0 (4.62) 33, -8.0 (4.22) 26, -23.3 (12.00)

15, -6.4 (7.94) 33, -4.8 (3.87) 24, -19.1 (15.10)

-4.6 (-9.5–0.3) -3.2 (-5.2 to -1.3) -4.2 (-11.8–3.4)

16, -16.7 (7.22) 62, -8.5 (8.90)

15, -8.5 (8.36) 61, -7.6 (9.30)

-8.2 (-13.7 to -2.7) -0.9 (-4.1–2.3)

Melancholia scale Anderson 1994

33, -7.2 (4.22)

33, -4.3 (3.67)

-2.9 (-4.8 to -1.0)

ZDRS Lipsey 1984

11, -23.0 (7.28)

15, -12.0 (13.98)

-11.0 (-19.3 to -2.7)

Prevention trials HDRS Dam 1996a Dam 1996b Robinson 2000a Robinson 2000b

16, -3.7 (6.17) 14, -2.8 (5.65) 13, 0.8 (3.75) 13, -1.2 (3.62)

8, -1.3 (5.75) 8, -1.3 (5.75) 8, -0.2 (3.95) 7, -0.2 (3.95)

-2.4 (-7.4–2.6) -1.5 (-6.5–3.5) 1.0 (-2.4–4.4) -1.0 (-4.5–2.5)

ZDRS Raffaele 1996

11, -17.9 (10.62)

11, -2.0 (10.4)

-15.9 (-24.7 to -7.1) -10

-5 Favors treatment

0 5 Favors control

Note that this figure should be interpreted cautiously in view of the small sample sizes, small number of trials and reporting this end point, and the multiple methods used within and between trials to assess depression. Effect sizes are differences in mean scores: error bars represent the 95% confidence interval (CI). Reproduced with permission from Hackett et al.: Stroke 36, 1092–1097 (2005) BDI: Beck Depression Inventory; CGI: Clinical Global Impression of Depression; HDRS: Hamilton Depression Rating Scale; MADRS: Montgomery Asberg Depression Rating Scale; ZDRS: Zung Depression Rating Scale.

instance [6,9,52]. Consideration may then be given to maintenance treatment for at least 6 months to reduce the risks of relapse. However, there are concerns regarding the gap between the efficacy of antidepressants demonstrated in controlled clinical trials, and their somewhat lower effectiveness in real-world settings [32]. Treating physicians should therefore take special note of issues such as comorbidity and polypharmacy in older, frailer, stroke patients. Psychotherapy

Psychologic therapies are the preferred method of treatment for mild mood disorders. Psychotherapy is a general term that refers to the treatment of psychologic disorders using planned and structured 100

interventions aimed at influencing behavior, mood and emotional patterns of reacting. There are a variety of psychotherapeutic methods used for depressive disorders that are of varying value to different people, including cognitive behavioral therapy (CBT) and problem solving therapy (PST). CBT focuses on changing cognitive patterns in order to change behavior and emotional state. PST targets depression by systematically teaching patients skills for improving their ability to deal with their own specific everyday problems and life crises, rather than developing generic skills. Psychotherapy should be provided by trained health professionals, usually psychiatrists, psychologists, psychotherapists or qualified counselors, although it is increasingly being used by Aging Health (2005) 1(1)

Treatment options for post-stroke depression in the elderly – REVIEW

trained nurses in primary care settings. In general, approximately 6–8 sessions should be provided to patients over 10–12 weeks, with most people experiencing an improvement in mood and/or a reduction in symptoms after 2 months of therapy. Response to therapy should be reviewed after eight sessions. If a person has multiple issues, or severe comorbidity, therapy may need to be extended for a further 6 months. The authors conducted two systematic reviews, using Cochrane Review methodology, of randomized controlled trials of psychotherapy used either selectively for treatment, or more generally for prevention, of depression following stroke [58,59]. One treatment trial with 121 patients at entry [60], and three prevention trials with 745 patients at entry were identified [61–63]. Further details are presented in the Cochrane Library version of these reviews [58,59]. Patients ranged in mean age between 66– 74 years. Patients were recruited up to 6 months after stroke onset; however, one trial did not specify the time from stroke onset to entry into the trial [61]. Most trials only excluded patients who were unable to partake in the intervention due to communication or cognitive difficulties, with one trial also excluding patients who had received treatment for depression in the previous 5 years. Two trials explicitly specified that the intervention was PST, one provided CBT and one provided an intervention that was more broadly defined. The interventions were delivered by a variety of trained professionals, including specialist nurses [60,61,63] and a mixed team of therapists. Therapy (an average of 5–12 sessions) continued for up to 1 year after randomization. In this review, no evidence was found that psychotherapy was effective in producing a remission of diagnosable depressive illness in stroke patients. A small, significant improvement (reduction) in psychologic distress was seen in the prevention trials. However, once again there was much heterogeneity both across and within studies, including variation in patient characteristics, methods of diagnosis and assessment of depression, and multiple end points. While there was also no evidence of harm through the reporting of adverse events, once again, adverse event data were seldom collected or reported adequately. Pharmacotherapy and psychotherapy have a high relapse rate following early discontinuation. CBT is the psychotherapy of choice for depressive disorders, with PST as a further treatment option if the patient indicates a preference for this method. Almost all antidepressants and www.futuremedicine.com

psychotherapies are equally effective for moderate depression in the general population, but CBT in combination with antidepressants gives better results than either treatment alone. For severe depression, psychotherapy may be used in addition to initial treatment with antidepressants to reduce residual symptoms and the risk of relapse [9], or in those with moderate or severe depression who refuse antidepressants. Electroconvulsive therapy

ECT involves the brief passage of an electrical current through the brain to induce a generalized seizure. The primary indication is severe depressive illness, or when a disorder, or its symptoms, are considered potentially life threatening. ECT must be administered by appropriately trained health professionals under accredited guidelines [64], and should only be used to achieve rapid and short-term improvement of severe symptoms after other treatments have proven ineffective. As the longer-term benefits and risks of ECT are unequivocal, and there are no double-blind, randomized controlled trials of ECT for the treatment of depression in stroke patients, it is not recommended as a primary or maintenance therapy for depression in this setting. However, case series indicate that the presence of stroke does not increase the risk of the procedure or treatment in patients with severe depression [64]. Barriers to effective therapy for depression General practitioners manage most (75%) of those who seek care for depression [65]. In an international study of pharmacotherapy for depression in primary care, the proportion receiving potentially effective treatment varied from 1–40%, with cost and concern regarding adverse effects of medication being the two most commonly reported barriers to treatment [66]. Approximately 40% of those with major depressive disorder are noncompliant with their treatment, and depressed medical patients are three-times more likely to be noncompliant than nondepressed ones. Patients who do not follow treatment advice do so for many different reasons, including stigma associated with antidepressants, inadequate education and support, adverse effects, drug interactions, complexity of dosing regimens, and lack of awareness about the sequelae and chronicity of mood disorders. Older adults may also lack appropriate social support, and increased forgetfulness may make them less likely to take their medication. Compliance with a particular treatment may be influenced by the relationship between therapist and patient [9]. 101

REVIEW – Hackett & Anderson

Simply providing support and information for stroke patients does not appear to result in improved outcomes [67]. Comprehensive multidisciplinary care management programs that offer education, training and goal setting, for patients and their caregivers, appear effective on a range of outcomes including mood [19,68]. The challenge now is to determine how best to apply such service models in a cost-effective manner to the broader stroke population, including those in poorer communities. Conclusion The impact of stroke on the individual is complex and multifaceted. While physical therapy has traditionally formed the cornerstone of stroke rehabilitation, there is increasing awareness that stroke and physical disability are not synonymous. To focus on purely physical manifestations of stroke can divert attention from potentially greater problems related to disturbance of mood and behavior that can impede patients from optimum recovery and readjustment to life after stroke. While it is clear that mood disorders associated with stroke are common and serious, there is very little direct reliable evidence to guide clinical management. The trials to date show promise for antidepressants but they have not addressed important clinical questions, in that the entry criteria have been narrow, and the results are difficult to apply widely. The complex inter-relationships of depressive symptoms with disability, medical illness, treatment adherence and other psychosocial factors may complicate the care of depressed older adults. There are a number of factors that may make treatment more difficult in the elderly, including the high rate of comorbid disorders and often an increased sensitivity to the side effects of medication. The extrapolation of findings in other patient groups indicates that antidepressants are beneficial in those with established depressive illness, and treatment with antidepressants should be continued for at least 6 months in those who respond to treatment. In view of the potential for adverse effects of medications and difficulties with the recognition of major depressive illness, psychotherapy has been advocated as an alternative. Mood disorders are one of the few potentially preventable and modifiable outcomes after stroke. Early identification of those with significant risk is of paramount importance for provision of early intervention and subsequent 102

reduction of burden. There is a need for good quality, randomized controlled trials to determine the broader use of specific psychotherapeutic strategies and antidepressants. Given that stroke patients are at a high risk of mood disorders for which no predictor variables have been identified, and for which currently available treatment strategies are relatively safe and low-cost, it seems reasonable to consider a broader use of antidepressants and/or psychologic therapies for several months after stroke onset with the aim of improving outcomes through the prevention of depression. However, for such a radical approach to be widely adopted in routine clinical practice will require guidelines based on high-quality randomized evidence. Future perspective Two undeniable successes of public health and medicine in the 20th and 21st centuries have been the avoidance of many communicable diseases and the aging of populations. However, the subsequent rapid increases in chronic diseases, including those affecting the brain, such as stroke and depression, now present major challenges. The dream of a reduction in the global burden of noncommunicable diseases and injury could be achieved in a large part through better community education and the eradication of poverty and smoking. However, this is unlikely to occur within the foreseeable future due to the dramatic restructuring and adverse lifestyle changes that are occurring in populations. Moreover, governments and industry are unlikely to shift their trade policies and practices to allow appropriate redistribution of wealth from the rich to the poor, within and between countries. However, advances in epidemiological and clinical research, together with a greater knowledge of the mechanisms of brain injury, degeneration and repair, suggest great potential for improving the outcomes from stroke and other neurologic diseases in some populations. In addition, benefits are likely to accrue from changes in healthcare delivery that include a greater use of population-based, patient-centered, well coordinated, multidisciplinary teams and clinical information system technologies to guide health practitioners in the effective implementation of costeffective interventions. With regards to stroke care, the goal of evidence-based systems to prevent and manage depression could be a reality in 5–10 years, albeit patchily applied in many parts of the world. Aging Health (2005) 1(1)

Treatment options for post-stroke depression in the elderly – REVIEW

Executive summary • Reducing the burden of stroke and other chronic diseases remains a challenge in aging populations. Other drives to improve healthcare systems include economic constraints, reduced hospital beds, and a refocus on the community for chronic disease management. • Depression is a major cause of disability in the community, and is an important complication of stroke affecting, on average, approximately one in three survivors of the illness. As well as having a negative influence on quality of life, ‘post-stroke depression’ is associated with reduced functioning and increased healthcare costs, informal caregiver stress, vascular events and mortality. • Complex relationships exist between vascular disease and depression. While there is increasing evidence to indicate that vascular risk factors, including ‘silent’ cerebrovascular disease, are associated with depression in later life, it remains controversial as to whether it is the specific location of the stroke lesion that is causal in determining the onset of depression. • Although evidence is strong for a link between depression and physical functioning in stroke patients, as it is among older people in general, it is uncertain how effective antidepressants and other depression management strategies are at improving stroke outcomes. • The benefits of antidepressants are well established. Yet, it is uncertain how these drugs are most appropriately applied in stroke patients with depressive symptoms that do not clearly fulfill diagnostic criteria for major depression. Advances in the better identification of depression, including screening and follow-up, will be restricted by the limitations of questionnaires and availability of specialist expertise in healthcare systems. • Given that stroke patients are at a high risk of mood disorders for which no predictor variables have been identified, and for which currently available treatment strategies are relatively safe and low-cost, it seems reasonable to consider a broader use of antidepressants and/or psychologic therapies for several months after stroke onset with the aim of improving outcomes through the prevention of depression. However, high-quality randomized evidence is required to justify such a new approach in routine clinical practice.

Bibliography Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers. 1. Hankey GJ, Jamrozik K, Broadhurst RJ, Forbes S, Anderson CS: Long-term disability after first-ever stroke and related prognostic factors in the Perth Community Stroke Study, 1989–1990. Stroke 33, 1034–1040 (2002). 2. Rothwell PM, Coull AJ, Giles MF et al.: Change in stroke incidence, mortality, casefatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 363 (Suppl.), 1925– 1933 (2004). • Pivotal population-based stroke incidence trends study showing declines in major stroke rates over 20 years in Oxford, UK. 3. Gustafson Y, Nilsson I, Mattsson M, Åström M, Bucht G: Epidemiology and treatment of poststroke depression. Drugs Aging 7, 298– 309 (1995). • IInteresting earlier overview on the importance of poststroke depression. 4. Murray CJ, Lopez AD: The Global Burden of Disease. A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. Harvard School of Public Health on Behalf of the World Health Organization and the World Bank, Cambridge, MA, USA (1996).

www.futuremedicine.com

5.

6.

7.

• 8.

9.

10.

11.

12.

Peveler R, Carson A, Rodin G: Depression in medical patients. Br. Med. J. 325, 149–152 (2002). World Health Organization: The World Health Report 2001: Mental Health: New Understanding, New Hope. WHO, Geneva, Switzerland (2001). Schulberg HC, Katon WJ, Simon GE et al.: Best clinical practice: guidelines for managing major depression in primary medical care. J. Clin. Psychiatry 60(Suppl. 7), 19–26 (1999). Guidelines for the management of major depression in clinical practice. Judd LL, Schettler PJ, Akiskal HS: The prevalence, clinical relevance, and public health significance of depressions. Psychiatr. Clin. North Am. 25, 685–698 (2002). Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Depression: Australian and New Zealand clinical practice guidelines for the treatment of depression. ANZ J. Psychiatry 38, 389–407 (2004). Unützer J, Patrick DL, Diehr P et al.: Quality adjusted life years in older adults with depressive symptoms and chronic medical disorders. Psychogeriatrics 12, 15–33 (2000). Katona CLE, Watkin V: Depression in old age. Rev. Clin. Gerontol. 5, 427– 441(1995). Weissman MM, Bland RC, Canino GJ et al.: Cross-national epidemiology of

13.



14.

15.

16.

• 17.

18.

19.

major depression and bipolar disorder. JAMA 276, 293–299 (1996). Martin F: Comorbidity of depression with physical illnesses: a review of the literature. Ment. Health Care 4, 405–408 (2001). Review which emphasises the importance of comorbidity in the context of depressive illness. Glassman AH, Shapiro PA: Depression and the course of coronary artery disease. Am. J. Psychiatry 155, 4–11 (1998). Ensinck KT, Schuurman AG, van den Akker M et al.: Is there an increased risk of dying after depression? Am. J. Epidemiol. 156, 1043–1048 (2002). Baldwin RC, Anderson D, Black S et al.: Faculty of Older Age Psychiatry Working Group, Royal College of Psychiatrists. Guideline for the management of late-life depression in primary care. Int. J. Geriatr. Psychiatry 18, 829–838 (2003). Contemporary guidelines on the management of depression in older adults. Mulsant BH, Ganguli M: Epidemiology and diagnosis of depression in late life. J. Clin. Psychiatry 60, 9–15 (1999). Simon GE, Goldberg D, Tiemens BG, Ustun TB: Outcomes of recognized and unrecognized depression in an international primary care study. Gen. Hosp. Psychiatry 21, 97–105 (1999). Unützer J, Katon W, Callahan CM et al.: Collaborative care management in late-life

103

REVIEW – Hackett & Anderson

••

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

104

depression in the primary care setting: a randomised controlled trial. JAMA 288, 2836–2845 (2002). One of the few large-scale trials of service delivery models for the management of depression in older adults. Cole MG, Dendukuri N: Risk factors for depression among elderly community subjects: a systematic review and metaanalysis. Am. J. Psychiatry 160, 1147–1156 (2003). Parikh RM, Robinson RG, Lipsey JR, Starkstein SE, Fedoroff JP, Price TR: The impact of poststroke depression on recovery in activities of daily living over a 2-year follow-up. Arch. Neurol. 47, 785– 789 (1990). Robinson RG, Bolla-Wilson K, Kaplan E, Lipsey JR, Price TR: Depression influences intellectual impairment in stroke patients. Br. J. Psychiatry 148, 541–547 (1986). van de Weg FB, Kuik DJ, Lankhorst GJ: Poststroke depression and functional outcome: a cohort study investigating the influence of depression on functional recovery from stroke. Clin. Rehabil. 13, 268–272 (1999). Anderson CS, Linto J, Stewart-Wynne EG: A population-based assessment of the impact and burden of caregiving for longterm stroke survivors. Stroke 26, 843–849 (1995). House A, Knapp P, Bamford J, Vail A: Mortality at 12 and 24 months after stroke may be associated with depressive symptoms at 1 month. Stroke 32, 696–701 (2001). Morris PL, Robinson RG, Andrzejewski P, Samuels J, Price TR: Association of depression with 10-year poststroke mortality. Am. J. Psychiatry 150, 124–129 (1993). Stenager EN, Madsen C, Stenager E, Boldsen J: Suicide in patients with stroke: epidemiological study. Br. Med. J. 316, 1206 (1998). Burvill PW, Johnson GA, Jamrozik KD, Anderson CS, Stewart-Wynne EG, Chakera TMH: Prevalence of depression after stroke: the Perth Community Stroke Study. Br. J. Psychiatry 166, 320–327 (1995). Johnson GA: Research into psychiatric disorder after stroke: the need for further studies [comment]. ANZ J. Psychiatry 25, 358–370 (1991). Herrmann N, Black SE, Lawrence J, Szekely C, Szalai JP: The Sunnybrook stroke study: a prospective study of

31.

32.

••

33.

34.

•• 35.

••

36.

• 37.

38.

39.

40.

••

depressive symptoms and functional outcome. Stroke 29, 618–624 (1998). House A, Dennis M, Mogridge L et al.: Mood disorders in the year after first stroke. Br. J. Psychiatry 158, 83–92 (1991). Hackett ML, Yapa C, Parag V, Anderson CS: Frequency of depression after stroke: a systematic review of observational studies. Stroke 36, 1330-1340 (2005). Overview of observational studies that provide reliable data on the frequency and management of poststroke depression. House A, Dennis M, Hawton K, Warlow C: Methods of identifying mood disorders in stroke patients: experience in the Oxfordshire Community Stroke Project. Age Ageing 18, 371–379 (1989). Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M: The ‘vascular depression’ hypothesis. Arch. Gen. Psychiatry 54, 915–922 (1997). IImportant article that presents the concepts of vascular depression. Steffens DC, Krishnan KRR, Crump C, Burke GL: Cerebrovascular disease and evolution of depressive symptoms in the Cardiovascular Health Study. Stroke 33, 1636–1644 (2002). Data from a large-scale epidemiological study quantifying the association of cerebrovascular disease and depression in later life. Dieguez S, Staub F, Bruggimann L, Bogousslavsky J: Is poststroke depression a vascular depression? J. Neurol. Sci. 226, 53– 58 (2004). Overview of the etiology and predictors of poststroke depression. Mast BT, Azar AR, Murrell SA: The vascular depression hypothesis: the influence of age on the relationship between cerebrovascular risk factors and depressive symptoms in community dwelling elders. Aging Ment. Health 9, 146–152 (2005). Robinson RG, Shoemaker WJ, Schlumpf M, Valk T, Bloom FE: Effect of experimental cerebral infarction in rat brain on catecholamines and behaviour. Nature 255, 332–334 (1975). Bhogal SK, Teasell R, Foley N, Speechley M: Lesion location and poststroke depression: systematic review of the methodological limitations in the literature. Stroke 35, 794–802 (2004). Carson AJ, MacHale S, Allen K et al.: Depression after stroke and lesion location: a systematic review. Lancet 356, 122–126 (2000). Pivotal overview with meta-analysis of all studies investigating the association of

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

• 52.

53.

stroke lesion location and poststroke depression – the conclusion was of no association. Singh A, Herrmann N, Black SE: The importance of lesion location in poststroke depression: A critical review. Can. J. Psychiatry 43, 921–927 (1998). Robinson RG, Price TR: Poststroke depressive disorders: a follow-up study of 103 patients. Stroke 13, 635–641 (1982). Castillo CS, Starkstein SE, Fedoroff JP, Price TR, Robinson RG: Generalized anxiety disorder after stroke. J. Nerv. Ment. Dis. 181, 100–106 (1993). Gupta A, Pansari K, Shetty H: Poststroke depression. Int. J. Clin. Pract. 56, 531–537 (2002). American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. APA, Washington DC, USA (1994). Swartzman LC, Gibson MC, Armstrong TL: Psychosocial consideration in adjustment to stroke. Phys. Med. Rehabil. 12, 519–541 (1998). de Coster L, Leentjens AF, Lodder J et al.: The senstivity of somatic symptoms in poststroke depression: a discriminant analytic approach. Int. J. Geriatr. Psychiatry 20, 358–362 (2005). Spalletta G, Ripa A, Caltagirone C: Symptom profile of DSM-IV major and minor depressive disorders in first-ever stroke patients. Am. J. Geriatr. Psychiatry 13, 108–115 (2005). Catapano F, Galderisi S: Depression and cerebral stroke. J. Clin. Psychiatry 51 (Suppl. Sep), 9–12 (1990). Okamoto K, Ohsuka K, Shiraishi T, Hukazawa E, Wakasugi S, Furuta K: Comparability of epidemiological information between self- and intervieweradministered questionnaires. J. Clin. Epidemiol. 55, 505–511 (2002). Alexopoulos GS, Buckwalter K, Olin J, Martinez R, Wainscott C, Krishnan KRR: Comorbidity of late life depression: an opportunity for research on mechanisms and treatment. Biol. Psychiatry 52, 543–558 (2002). IImportance of comorbidity in the aetiology of depression in later life. National Collaborating Centre for Mental Health: Depression: management of depression in primary and secondary care. National Institute for Clinical Excellence, London, UK (2004). Guidelines for the Treatment and Management of Depression by Primary Healthcare Professionals. National Advisory

Aging Health (2005) 1(1)

Treatment options for post-stroke depression in the elderly – REVIEW

54. 55.

56.

57.

58.

••

Committee on Health and Disability, Wellington, New Zealand (1996). Marano E: How to take an antidepressant. Psychol. Today 58–95 (2003). Narushima K, Chan KL, Kosier JT, Robinson RG: Does cognitive recovery after treatment of poststroke depression last? A 2year follow-up of cognitive function associated with poststroke depression. Am. J. Psychiatry 160, 1157–1162 (2003). Kimura M, Robinson RG, Kosier JT: Treatment of cognitive impairment after poststroke depression: a double-blind treatment trial. Stroke 31, 1482–1486 (2000). Jorge RE, Robinson RG, Arndt S, Starkstein S: Mortality and poststroke depression: a placebo-controlled trial of antidepressants. Am. J. Psychiatry 160, 1823–182 (2003). Anderson CS, Hackett ML, House AO: Interventions for preventing depression after stroke. Cochrane Database Syst. Rev. (2), CD003689 (2004). Cochrane Stroke Group systematic review of randomised evidence for prevention strategies.

www.futuremedicine.com

59.

••

60.

61.

• 62.

63.

• 64.

Hackett ML, Anderson CS, House AO: Interventions for treating depression after stroke. Cochrane Database Syst. Rev. (3), CD003689 (2004). Cochrane Stroke Group systematic review of randomised evidence for prevention strategies. Lincoln NB, Flannaghan T: Cognitive behavioural psychotherapy for depression following stroke. A randomized controlled trial. Stroke 34, 111–115 (2003). Forster A, Young J: Specialist nurse support for patients with stroke in the community: a randomised controlled trial. Br. Med. J. 312, 1642–1646 (1996). Well designed trial of specialist stroke nurse support. Goldberg G, Segal ME, Berk SN, Schall RR, Gershkoff AM. Stroke transition after inpatient rehabilitation. Top. Stroke Rehabil. 4, 64–79 (1997). House A: The treatment of depression after stroke. J. Psychosom. Res. 48, 235 (2000). Overview of treatments for poststroke depression. Anderson C, Skegg P, Wilson R, Hackett M, Snelling J, Grover A: Use of Electroconvulsive

65.

• 66.

67.

68.

Therapy (ECT) in New Zealand: A Review of Efficacy, Safety and Regulatory Controls. Ministry of Health, Wellington, New Zealand (2005). Hickie I, Davenport T, Scott E: Depression: Out of the Shadows. A guide to Understanding Depression and its Treatment. The Australian Women’s Weekly Health Series. ACP Publishing and Media 21, Sydney, Australia (2003). Includes sections addressing barriers to the management of depression. Simon GE, Fleck M, Lucas R, Bushnell DM: Prevalence and predictors of depression treatment in an international primary care study. Am. J. Psychiatry 161, 1626–1634 (2004). Forster A, Smith J, Young J et al.: Information provision for stroke patients and their caregivers. Cochrane Database Syst. Rev. 3, CD001919 (2001). Kalra L, Evans A, Perez I et al.: Training carers of stroke patients: randomised controlled trial. Br. Med. J. 328, 1099–1104 (2004).

105