Clinical update • CLINICAL PRACTICE Poststroke

Fary Khan, MBBS, FAFRM (RACP), is Lecturer, Rehabilitation Studies, Department of Medicine, University of Melbourne, neuro-rehabilitation physician, the Melbourne Extended Care and Rehabilitation Centre, the Royal Melbourne Hospital, and Head, Orthopaedic and Musculoskeletal Unit, Caufield General Medical Centre, Victoria.

BACKGROUND is the leading cause of disability in PSD and functional recovery Poststroke depression (PSD) is common adults and is frequently associated with neu- and often unrecognised. The diagnosis ropsychiatric symptoms such as depressed Poststroke depression is associated with can be difficult due to deficits of stroke mood, generalised anxiety and apathy. The poor functional and psychosocial outcome.8 such as impaired self reporting and prevalence of poststroke depression (PSD) Although there is no long term data on the cognition, poor insight and dysphasia. varies from 25–79% due to the differences in direct effect of PSD on cost of care there are Untreated PSD can interfere with recovery various study diagnostic criteria, selection of reports of: and adversely affect functional and social patients, and the time elapsed since the • prolonged inpatient hospital length of stay4 outcomes. stroke. • greater disability with activities of daily Clinical depression is a common complica- living9 OBJECTIVE tion, and in some long term studies was • severe physical impairment10 This article outlines the diagnosis, shown to persist up to 3 years following • poor cognitive function11 pathophysiology and treatment for PSD. stroke.1,2 Depression decreases patients’ par- • poor participation in rehabilitation11 ticipation in rehabilitation and impairs • reduced social activity1 DISCUSSION functional recovery, community reintegration • poor language function1,2 The natural history of PSD suggests that and long term outcomes.3 It increases the cost • failure to return to work8, and most PSD is not immediate but develops of treatment and burden of care to families. • a higher mortality at 10 years.12 over months with peak prevalence The diagnosis of PSD can be difficult, between 6 and 24 months, and in some and is reported to have been missed in What causes PSD? cases persists up to 3 years following 50–80% of cases by nonpsychiatric physi- The aetiology of PSD is not well understood. stroke. General practitioners and treating cians.4 Longitudinal studies on the natural Different mechanisms for PSD may be specialists need to actively monitor history of PSD progression show that most involved in the aetiology of stroke over time patients for PSD. While depression is not immediate but develops and this has implications for treatment. medication is the mainstay of treatment over months with peak prevalence between Depression may be a result of: for PSD, psychotherapeutic interventions 6–24 months poststroke.5 Most major • a biologic effect of brain damage are important. Treatment should include depression remits in the 1–2 years following • a reaction to the losses caused by stroke, patient and family education, re- stroke, either spontaneously having run its or establishment of sleep pattern, addressing course or through treatment – it is rarely • a combination of these factors.13 functional difficulties, increasing chronic.6 Depression also occurs in 40% of Initially PSD may be caused by a neurophysio- community participation, improving diet primary care givers of patients with stroke logic imbalance and depression that develops and regular exercise. and is easily missed.7 later may be caused by psychological factors.1

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Biological effects of stroke found to be more depressed overall,2 younger be independent of the presence of depres- During the acute brain infarction there is patients tended to be depressed in the acute sion. However, depressed patients perform decreased monoamine synthesis (enzyme early stages following stroke.28 poorly in areas of cognition2 and have poorer inhibition during ischaemia) resulting in verbal abilities.29 Apathy is also seen in stroke decreased 5-HT levels. These have been Diagnosis patients and may coexist with emotional and implicated in altered mood,14 sleep, and The diagnosis of PSD may be difficult due to cognitive poststroke disturbances. appetite.15 The use of agents deficits in limited patient self report, impaired Symptoms of depression may be due to has therefore been suggested to augment cognition, poor insight and aphasia. Features an underlying medical condition or cognitive stroke recovery.16 Stroke patients with such as anosognosia, , emotionalism, deficits rather than an underlying mood disor- depression may also have: apathy and intellectual decline can also limit a der. Differential diagnoses include organic • altered cortical receptor activity17 patient’s ability to express themself. This brain syndrome, side effects of medications, • altered concentration of cerebrospinal may result in discrepancy between self rated sepsis and hypothyroidism. fluid neurotransmitter metabolites18 depression and observer rated depression. A number of standardised tests are used • electrophysiological abnormalities19, and Distinguishing between cognitive decline to screen patients for depression or to • decreased cerebral blood flow.20 due to stroke and poor cognitive function monitor their response to treatment, but Lesions in the left frontal lobe or basal secondary to depression can be difficult in these should not be used for diagnosis in iso- ganglia are reported to cause more PSD than this group of patients. Stroke is followed by lation (Table 1). The Hospital Anxiety and other brain areas.21 There is no clear associa- decline in cognitive function that appears to Depression Scale (HADS) and the General tion between the volume of the lesion22 and cortical/subcortical atrophy23 with the type or Table 1. Screening tools for depression and recommendations33 severity of depressive symptoms. Psychosocial effects of stroke Hospital Anxiety and Depression Scale Seven items each measuring depression and anxiety. Originally used in 100 patients Despite successful rehabilitation for mobility 16–65 years of age in outpatient settings. It has high reliability and validity, and only and self care skills, social reintegration and 1% false positives and negatives. Correlations with psychiatric ratings were 0.79 for depression and 0.54 for anxiety. Recommended by the British Stroke Research group life satisfaction remain an issue for many stroke patients. Stroke is associated with sig- Beck Depression Inventory nificant psychosocial difficulties that can Recommended scale in integrated pathway of PSD. Twenty-one item self report impact on the development of depression instrument with low reliance on somatic items. Respondents are asked how they have been feeling over the past 2 weeks. Each item is rated on a 4 point scale, including: ranging from 0–3. A cut off of 14/15 is indicative of depression. It has good reliability • grief at loss of function, loss of indepen- and validity and has a positive predictive value of 0.54 and negative predictive value dence or loss of employment of 0.99, and few false negatives. It has high internal consistency. Factor analysis can • financial difficulties discriminate between those with cognitive and noncognitive dimensions. The • social isolation advantage in stroke patients is the low demand on memory • poor self esteem, and General Health Questionnaire-28 (GHQ-28) • relationship or sexual difficulties. Uses 28 items for somatic symptoms, anxiety, insomnia, social dysfunction and Early factors predictive of PSD include: severe depression. It is widely used, acceptable for the elderly patients, sensitive to • aphasia at 3–12 months poststroke the effects of intervention and recommended by the British Stroke Research group. It • older age has good reliability and validity. Coefficient correlations between GHQ-28 and interview measures are 0.67 and 0.83 with a median of 0.76. The sensitivity ranged • limited social supports from 0.44–1.0 and specificity ranged from 0.7–0.93 • living alone, and Depression, Anxiety, Stress Scale (DASS) • a previous history of psychiatric This dimensional scale contains 42 questions, with 14 items subdivided into 2–5 problems.24 items. It assesses self reports on depression, hopelessness, anxiety and stress levels. There is conflicting evidence regarding DASS has high internal consistency and yields meaningful discriminations in a gender and PSD. In one study, women were variety of settings found to be more depressed after stroke,25 26 but another found otherwise. When fol- Other depression screening tools include: Hospital Stroke Aphasic Depression lowed up, the male PSD patients had a Questionnaire, Brief Assessment Schedule for Depression Cards, Geriatric Depression poorer prognosis compared with women Scale, Signs of Depression Scale, and Visual Analogue Mood Scale patients.27 Although older patients were

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Health Questionnaire (GHQ) are the best work support; they have not demonstrated coping skills as detailed below. validated scales in patients without commu- any clear benefit on mood state.31 Cognitive Pharmacological management nication problems and are probably the most behaviour therapy (CBT) results are encour- useful for screening stroke patients without aging but these treatments are not always Selective serotonin reuptake inhibitors communication difficulties in the rehabilita- accessible. Language limitations and cogni- (SSRIs) are the most commonly used drugs tion or community setting. Those who score tion issues in stroke patients can interfere for PSD. Tricyclic (TCAs) are more than eight for depression on the HADS with psychotherapy interventions including less commonly used and inhibit the uptake should be further assessed. CBT. In the weeks and months after the of both serotonin and noradrenaline. There Full history, examination, and patient and stroke, the residual cognitive and behav- is no high level evidence to suggest SSRIs family reports are important. The DSM IV ioural deficits are common causes for failure are superior to TCAs. In a double blind, criteria for major depression are listed in to return to premorbid levels of interper- placebo controlled study, was Table 2. The normal exclusion of symptoms sonal, vocational and recreational compared with – the response due to an underlying medical condition is functioning. Patients with behavioural prob- was adequate with both drugs, but only the waived in PSD.30 Older patients may experi- lems that are difficult to manage may be nortriptyline group improved functional inde- ence depression without sadness, but they treated with success in specialised care pendence.32 However, SSRIs have a safer may present with anxiety and a general where behaviour is monitored, assessed side effect profile, a relatively quick onset of sense of hopelessness. and subjected to positive or negative rein- action of 7–10 days, and good anxiolytic forcers. In such patients, giving feedback effects making them first line antidepres- Treatment and support assists in engaging the patient sant, especially in the elderly. Treatment for PSD involves a combination in rehabilitation treatment and improves Within a class, there is no hard data to of patient education, antidepressant medica- compliance. recommend one drug over another for PSD, tion, behavioural strategies and In practice, antidepressants are often the however, a recent review32 suggested an psychotherapy. most pragmatic solution, with more involved optimum regimen for sertraline with a start- A number of psychosocial interventions psychotherapy reserved for antidepressant ing dose of 50 mg per day, which can be have been studied. These interventions resistant cases or those who are unable to increased to 100 mg per day in 2 weeks. included controlled trials of counselling, tolerate medication. Patients still benefit There is little benefit from a higher dosage, occupational therapy for leisure, and social from pyschoeducation and learning new and if there is no benefit after 4–6 weeks on 100 mg, then it should be discontinued. It Table 2. DSM IV criteria for major depression should be continued for at least 6 months and slowly weaned but can continue if The American Psychiatric Association Diagnostic and Statistical Manual of Mental symptoms recur. Sertraline is also effective Disorders (4th edn) (DSM-IV) list the following criteria for diagnosis of depression: in the treatment of emotionalism following Five or more of the following symptoms persisting over a 2 week period causing stroke. Electroconvulsive therapy has been clinically important distress or impairing work, social or personal functioning (with used to treat refractory severe PSD but is depressed mood or decreased interest or pleasure as one of the five): limited due to side effects. • depressed mood most of the day, occurring most days (subjective or observed) Nonpharmacological treatment • markedly diminished interest or pleasure most of the day, nearly every day Psychosocial management strategies • significant weight or appetite change include: • insomnia or hypersomnia • education about depression to the • psychomotor agitation or retardation (observable by others) patient, carer and family • managing sleep-wake cycles • fatigue or loss of energy • improving nutrition • feelings of worthlessness or inappropriate guilt • anxiety management techniques • diminished ability to concentrate or make decisions • problem solving techniques • recurring thoughts of death or suicide plans • behavioural programs to target specific issues (eg. apathy, aggression) 30 Note: the normal exclusion of symptoms due to an underlying medical condition is waived in PSD • cognitive remediation (Table 1) • compensatory rehabilitation strategies for specific physical problems (eg. spas-

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ticity, pain) patient. Gen Hosp Psychiatry 1992;14:69–76. Sunnybrook Stroke study: a prospective study 10. Parikh RM, Robinson RG, Lipsey JR, et al. The of depressive symptoms and functional out- • addressing relationship difficulties (eg. impact of poststroke depression on recovery in comes. Stroke 1998;29:618–624. altered family role, intimacy issues, self activities of daily living over a 2 year follow 26. Berg AL, Palomaki H, Lehtihalmes MLP, et al. image) up. Arch Neurol 1990;47:785–789. Poststroke depression: 18 month follow up. 11. Sinyor D, Amato P, Kaloupek DG, et al. Stroke 2003;34:138–143. • provision of aids and adaptive equipment Poststroke depression: relationships to func- 27. Burvill PW, Johnson GA, Jamrozik KD, et al. to optimise physical fitness and maximise tional impairments, coping strategies and Prevalence of depression after stroke: the function and community participation rehabilitation outcomes. Stroke Perth Community Stroke Study. Br J Psychiatry 1986;17:1102–1107. 1995;166:320–327. • daily activity planning and reduction of 12. Morris P, Robinson R, Andrzejewski P, et al. 28. Robinson RG, Kubos KL, Rao K, Price TR. social isolation Association of depression with a 10 year post- Mood changes in stroke patients: relationship • improving patient and carer support, and stroke mortality. Am J Psychiatry to lesion location. Compr Psychiatry • fatigue management and energy conser- 1993;150:124–129. 1983;24:555–566. 13. Roth EJ. Stroke. In: PM & R Secrets. O’Young 29. Berg A, Palomaki H, Lehtihalmes M, et al. vation strategies. B, Young M, Steins S, eds. Philadelphia: Hanley Poststroke depression in acute phases after & Belfus, 1997;253–262. stroke. Cerebrovasc Dis 2001;12:14–20. Conclusion 14. Meltzer HY, Lowy MT. Serotonin hypothesis of 30. Rigler SK. Management of poststroke depres- depression. In: Meltzer HY, ed. sion in older people. Clin Geriatr Med General practitioners play a pivotal role in the Psychopharmacology: the third generation of 1999;15:765–783. ongoing care and management of patients progress. New York, NY: Raven Press, 31. Turner-Stokes L, Hassan N. Depression after recovering from stroke – and their families. 1987;513–526. stroke: a review of the evidence base to inform 15. Sonbrie P. Reconciling the role of central sero- the development of an integrated care Early screening, monitoring and treatment for tonin neurons in human and animal behaviour. pathway. Part 1: diagnosis, frequency and depression after stroke can facilitate a Behav Brain Res 1986;9:319–364. impact. Clin Rehab 2002;16:231–247. patient’s functional recovery, social reintegra- 16. Ramasubbu R, Flint A, Brown G, et al. 32. Robinson JR, Schultz SK, Castillo C, et al. tion and improve their quality of life. Diminished serotonin mediated prolactin Nortriptyline versus fluoxetine in the treat- responses in nondepressed stroke patients ment of depression and in the short term compared with healthy normal subjects. Stroke recovery after stroke: a placebo controlled Conflict of interest: none declared. 1998;29:1293–1298. double blind study. Am J Psychiatry 17. Barry S, Dinan TG. Alpha 2 adrenergic receptor 2000;157:351–359. References function in poststroke depression. Psychol 33. Bennett HE, Lincoln NB. Screening for mood 1. Astrom M, Adolfson R, Asplund K. Major Med 1990;20:305–309. disorders after stroke. Stroke Association and depression in stroke patients: a 3 year longitu- 18. Bryer JB, Starkstein SE, Votypka V, et al. the NHS Changing Workforce Program. School dinal study. Stroke 1993;24:976–982. Reduction of CSF monoamine metabolites in of Psychology, University of Nottingham UK. 2. Kauhanen ML, Korpelainen JT, Hiltunen P, et poststroke depression: a preliminary report. J March 2004; in press. al. Poststroke depression correlates with cogni- Neuropsychiatry 1992;4:440–442. tive impairment and neurological deficits. 19. Kapen S, Greiffenstein M. Stroke and depres- AFP Stroke 1999;30:1875–1880. sion: the cholinergic REM sleep induction test. 3. McGuire JR, Harvey RL. The prevention and In: Horne J, ed. Sleep 1988. New York, NY: management of complications after stroke. Gustav Fischer, 1989;238–240. Phys Med Rehab Clin North Am 20. Grasso MG, Pantano P, Ricci M, et al. Mesial 1999;4:857–874. temporal cortex hypoperfusion is associated 4. Schubert D, Burns R, Para W, et al. Increase of with depression in subcortical stroke. Stroke medical hospital length of stay by depression 1994;25:980–985. in stroke and amputation patients: a pilot 21. Starkstein SE, Cohen BS, Federoff P, et al. study. Psychother Psychosom 1992;57:61–66. Relationship between anxiety disorders and 5. Robinson RG, Bolduc PL, Price TR. Two year depressive disorders in patients with cere- longitudinal study of poststroke mood disor- brovascular injury. Arch Gen Psychiatry ders: diagnosis and outcome at 1 and 2 years. 1990;47:246–251. Stroke 1987;18:837–843. 22. Herrmann M, Bartels C, Wallesch CW. 6. Parikh RM, Lipsey JR, Robinson RG, Price TR. Depression in acute and chronic aphasia: A two year longitudinal study of poststroke symptoms, pathoanatomo clinical correlations, mood disorders: prognostic factors related to 1 and functional implications. J Neurol and 2 year outcome. Int J Psychiatry Med Neurosurg Psychiatry 1993;56:672–678. 1988;18:45–56. 23. Starkstein SE, Robinson RG, Price TR. 7. Kotila M, Numminen H, Waltimo O, Kaste M. Comparison of patients with and without post- Depression after stroke: results of the stroke major depression matched for size and FINNSTROKE study. Stroke 1998;29:386–372. location of lesion. Arch Gen Psychiatry 8. Neau JP, Ingrand P, Mouille-Brachet C, et al. 1988;45:247–252. Functional recovery and social outcome after 24. Anderson G, Vestergaard K, Ingemann-Nielson cerebral infarction in young adults. M, Lauritzen L. Risk factors for poststroke Cerebrovasc Dis 1998;8:296–302. depression. Acta Psychiatr Scand 9. Schubert D, Taylor C, Lees S, et al. Physical 1995;92:193–198. Correspondence consequences of depression in the stroke 25. Herrmann N, Black SE, Lawerence J, et al. The Email: [email protected]

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