Malaysian Healthy Ageing Society Professor David Ames BA MD - - PowerPoint PPT Presentation

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Professor David Ames BA MD FRCPsych FRANZCP University of Melbourne Professor of Ageing and Health Director National Ageing Research Institute PO Box 2127, RMH, 3050, Victoria dames@unimelb.edu.au

Detection and management of late life depression

SYMPTOMS OF DEPRESSION

• Low mood
• Loss of interest
• Lack of energy
• Sleep disturbance
• Appetite/weight change
• Agitation or retardation
• Guilt
• Thoughts of death/suicide
• Poor concentration
• Loss of confidence

Is late life depression different from depression at earlier ages? (1)

• Depression at all ages has similar core features
• The elderly are more likely than the young to have

comorbid dementia or physical ill health or to have been recently bereaved.

• Current diagnostic criteria proscribe the allocation
• f a primary depressive diagnosis in some of

these circumstances.

• Some elderly people with depressive syndromes

get classed as having an organic mood disorder, dementia with depressed mood or normal bereavement reaction.

Is late life depression different from depression at earlier ages? (2)

• Less subjective lowering of mood
• Fewer suicidal thoughts
• More hypochondriasis
• More somatic complaints
• More weight loss
• More constipation
• More frequent subjective and objective cognitive

difficulty

• These studies relate to hospital inpatients and

maybe biased by variable admission thresholds for individuals at different ages

EPIDEMIOLOGY

Severe/major depressions 0.5 to 3% Mild/non major depressions 6 to 20% Women : men 7 : 3 Physical ill health, stressful life events and poor social support are risk factors

Depression is far more common among those in residential care and among elderly people in general hospital wards than among those living at home.

AETIOLOGY OF LATE LIFE DEPRESSION

• Genetics
• Sex
• Age related physiological or anatomical change
• Physical illness/disability
• Substance use and iatrogenesis
• Personality factors
• Social factors
• Adverse life events

GENETICS

With age genetic factors become less important, accounting for 8% rather than 20% of the variance in the occurrence of late life depression

SEX

As at all ages women are more prone to depression than men. Male rates of depression come closer to female rates at the more severe end of the spectrum.

AGE RELATED PHYSIOLOGICAL CHANGES

• Alterations in cortisol secretion
• TRH/TSH alterations

AGE RELATED NEUROANATOMICAL CHANGE

• Larger ventricles
• Increased deep white matter lesions
• Sulcal widening

DEEP WHITE MATTER LESIONS

• To be distinguished from periventricular lesions
• Appear to predispose to first onset depression

in late life

• Appear to worsen prognosis

DWMHs AND LATE ONSET DEPRESSION

• Excess of large DWMHs in patients with late onset

psychotic depression (Lesser et al., 1991)

• Late onset major depression associated with higher rate of

caudate HIs and large DWMHs compared to early onset major depression (Figiel et al., 1991)

• Late onset and negative family history for mood disorders

are associated with more severe DWMH (Hickie et al., 1995)

• Many investigators have seen higher prevalence of severe

WHIs in late onset depression compared to early onset depression with few negative findings

DEPRESSION IS HIGHLY PREVALENT IN PATIENTS WITH CEREBROVASCULAR DISEASE

• 30% to 50% of patients had depression at initial evaluation

after stroke (Robinson and Starkstein 1999)

• Cerebrovascular disease frequently observed in patients with

late onset depression

• Patients with hypertension, CAD, diabetes and vascular

dementia often have depression

• Relationship between depression and cerebrovascular disease

– Depression may be an understandable psychological response to stroke – Depression may be a direct consequence of ischaemic brain damage

• r focal neurological lesions

– Depression may be a risk factor to both for stroke or vascular risk factors – Both conditions (depression and cerebrovascular disease) may co- exist by chance

POST STROKE DEPRESSION (PSD)

• Occurs in 20% to 50% of patients in the first year

after stroke (House et al., 1991; Robinson et al., 1987)

• Rate of major depression may be 0% to 25%
• Rate of minor depression may be 10% to 30%
• Controversial whether this is more common than in

patients with other severe physical illnesses

• Depression is not the only psychiatric disorder to

emerge after stroke

MECHANISMS OF POST STROKE DEPRESSION Lesions affecting frontal subcortical circuits within the basal ganglia seem to be connected to post stroke depression

VASCULAR DEPRESSION

• Late onset depression
• Reduced depressive ideation (e.g. guilt)
• Reduced insight
• More overall morbidity
• Apathy and retardation
• More cognitive impairment
• Poorer recovery from depression

PHYSICAL ILLNESS/DISABILITY

• The strongest association with late life depression
• e.g. r = 0.4 in US/UK study
• Urinary incontinence
• Chronic pain
• Activity limitation

DEPRESSION IN CARDIOVASCULAR DISEASE

• Psychiatric disorders following MI are common
• Detectable in 1/3 people following MI while in hospital
• Half of these people have major depression that is likely to persist
• Major depression may be associated to adverse outcomes including

increased mortality, morbidity and delayed return of functioning

• Major depression particularly common in subjects with prolonged

history of cardiac disease prior to MI, multiple psychosocial stressors and past history of depression

• This depression is particularly likely to be associated with adverse
• utcomes when it is not a first episode but represents a relapse or

recurrence

SUBSTANCE USE

• Alcohol and other substances

IATROGENESIS

• A wide range of therapeutic compounds has the

potential to initiate a worsened depression

• Anti-hypertensives
• NSAIDs
• Sedatives
• etc

Effect Drug Groups Implicated Linked to depression Steroids, clonidine, calcium channel blockers, digoxin Possible link to depression Statins, beta blockers, ACE inhibitors Possible link to increased suicide risk Beta blockers, calcium channel blockers

DRUG GROUPS IMPLICATED IN DRUG INDUCED MOOD CHANGE

IATROGENESIS

A wide range of therapeutic compounds has the potential to initiate a worsened depression

• Anti-hypertensives
• NSAIDs
• Sedatives
• etc

PERSONALITY FACTORS

The DSM IV clusters can be stereotyped as the weird, the wild and the worried. Studies of personality difficulties in late life are few and far between. Some older people with personality difficulties survive to old age. These individuals are likely to have fewer social supports and are more likely to enter residential care because of decreased social contact.

SOCIAL FACTORS

• Isolation
• Entry to residential care
• Narcissistic society
• Societal view of ageing

CONSEQUENCES OF DEPRESSION

• Not trivial
• May affect incidence and outcome of physical disorders

COMMUNITY STUDIES

• At least eight well designed large community based studies

examined the association between depression and development of cardiovascular disease

• All but one has shown an association between depression

and development of cardiovascular disease after controlling for pre-existing cardiovascular disease, use of antidepressants and other coronary risk factors including smoking

• Depression predicts:

(i) deaths from cardiovascular disease (RR 1.5 to 3.9) (ii) deaths from CHD (RR 1.3 to 5.2) (iii) MI (RR 1.7 to 4.5) (iv) Development of symptomatic IHD/angina (RR 2.1 to 4.6)

IMPACT OF AFFECTIVE DISORDERS ON THE COURSE OF ESTABLISHED CARDIOVASCULAR DISEASE

• In ambulant patients with IHD prevalence of major depression

is approximately 1.5 x general population rate

• At the time of MI depression prevalence is 3 to 4 x general

population (13 to 19%)

• 26% of those with cardiac failure have major depression
• 17% of those with other cardiac disorders have major

depression

• Rates lowest in outpatients, highest in more severely ill

patients

• Depression in cardiovascular patients is associated with

increased mortality, increased morbidity (angina, arrhythmias, re-hospitalisation and delayed return to work) and reduced quality of life

DEPRESSION AND MORTALITY

• Major depression following MI is associated with an

increased risk of mortality at 6 months (hazard ratio 4.3) (Frasure-Smith et al., 1993)

• Association remains after controlling for severity of

physical factors related to infarct and has been found in other studies with relative risk varying from 1.4 to 2.5 after adjustment

• Other studies by Frasure-Smith and colleagues

reinforce the presence of this association

896 Post MI patients (Lesperance et al., 2002)

5 year risk of cardiac mortality and depressive symptoms

RELATIVE RISK OF MORTALITY

• Depression 3.54
• Left ventricular failure 3.59
• Diabetes 2.72

(Welin, 2000)

EFFECT OF DEPRESSION ON OUTCOME FOLLOWING STROKE

• Most studies demonstrate greater functional impairment in depressed

patients

• In one 10 year study likelihood of dying was 3.5 times higher for

depressed than non-depressed patients after controlling for demography, comorbid illness, prior stroke on medication, physical and cognitive impairment and lesion parameters (Morris et al 1993).

• Patients with high depressive symptom scores in a large cohort of elderly

subjects with diagnosed hypertension were 2.3 to 2.7 times more likely to suffer from stroke than non depressed hypertensive patients (Ramasubbu, 2000)

• In a 29 year followup population study of 6676 stroke free adults baseline

depressive symptoms were associated with increased risk of stroke mortality

Physical Management of Depression in late Life

• ECT
• Antidepressants
• Mood stabilisers

ECT

• Electro-convulsive therapy is the most

effective treatment for the severely depressed older patient especially if delusions or hallucinations are present.

• Initial super threshold unilateral application is
• recommended. Available RCTs could be

improved but the database is large.

Electro Convulsive Therapy (ECT)

• No absolute contraindications to ECT
• Cardiovascular events are the leading cause of morbidity

and mortality post ECT

• Patients with known cardiac disease have increased risk
• f cardiac complications during ECT
• Assess relative risk of complications versus the morbidity

and mortality of untreated depression

• ECT has been used safely in patients with impaired

cardiac output, cardiac aneurysm, post stroke depression, aortic aneurysm, aortic stenosis, atrial fibrillation, anti coagulant therapy, pacemaker patients

MEDICATION

• Available data from over 70 RCTs suggest that

antidepressants are efficacious in 50% to 60% of elderly patients with depression compared with about 30% for patients on placebo.

• New generation antidepressants such as SSRIs are better

tolerated by elderly people than more established tricyclic drugs.

• More research is needed of the efficacy and tolerability of

antidepressants in those with comorbid depression and dementia of serious physical illness.

• Lithium may be useful in individuals with multiple relapses.

SADHART STUDY

Glassman et al. (2002) JAMA, 288: 701 - 709

369 post MI or UA patients with MDD (HDRS mean 19.6) randomised to sertraline 50 – 200 mg (n = 186) or placebo (n = 183) for 24 weeks.

SADHART RESULTS CGI responder rates were 67% sertraline and 53% placebo (p = 0.01). For those with one or more prior depressive episodes the rates were 72% vs 51% (p = 0.003) and for severe depression 78% v 45% (p = 0.001). Sertraline was as well tolerated as placebo and the rate of severe cardiac adverse events was 14.5% on sertraline, 22.4% for placebo.

DOUBLE BLIND PLACEBO CONTROLLED STUDIES OF ANTIDEPRESSANT DRUGS GIVEN TO STROKE PATIENTS

There are 5 studies in the literature which have assessed nortritypline, trazodone, citalopram and fluoxetine. The smallest study had 27 patients and the largest had 66.

SERTRALINE FOR STROKE ASSOCIATED MOOD LABILITY (Burns et al., 1999)

• 28 non depressed patients with post stroke mood lability

took part in an 8 week double blind placebo controlled trial

• f sertraline (50 mg per day) versus placebo
• Statistically significant improvements were seen in a

global rating of emotionalism and a specific benefit on tearfulness for patients receiving sertraline

• 50 mg of sertraline per day may be an effective and well

tolerated treatment for stroke associated lability of mood

• In earlier studies some response to amitriptyine, fluoxetine

and citalopram was seen

SERTRALINE AS PROPHYLAXIS AGAINST POST STROKE EMOTIONAL LABILITY RASMUSSEN ET AL. (POSTER)

• 138 patients examined in first 4 weeks after stroke, 118 entered the trial

with Sertraline or placebo

• 17% had pathological crying at baseline (11 placebo, 9 treatment)
• Number of patients with pathological crying decreased faster in

Sertraline group.

• 16 patients developed pathological crying on Sertraline but only 2 had it

when they left the study

• 20 patients developed pathological crying in the placebo group and 12

still had it when they left the study

• Sertraline eliminated pathological crying in 88% of patients versus 40%

for placebo

LACK OF RANDOMISED CLINICAL TREATMENT TRIALS

• Apart from SADHART there is a lack of randomised

clinical treatment trials in depressed patients with IHD

• Recent Cochrane review addressed the issue of

antidepressant treatment in the physically ill and recommended treating with antidepressants was effective and that there is no difference between placebo and antidepressants in the number of people who drop out of

• studies. However, only one study addressing heart

disease met inclusion criteria

CARDIAC ARRYTHYMIA SUPPRESSION TRIAL (CAST), 1992

• CAST was designed to determine whether anti-

arrhythmic agents would help control ventricular irritability and arrhythmias post MI

• There was a significant increase in mortality in

those treated with class 1A or 1C agents compared to placebo

• TCAs have similar electro physiological

characteristics to type 1A (Moricizine) anti- arrhythmics

SPECIFIC ANTIDEPRESSANTS

• TCAs: orthostatic hypotension, slowing of cardiac conduction,

electrophysiological properties of type 1 anti-arrhythmic, Nortriptyline less likely to cause postural hypotension than other TCAs

• TCAs have no significant effect on left ventricular function
• MIANSERIN: Evidence suggests it has a low cardiotoxicity but NB risk of

bone marrows suppression

• SSRIs: Bradycardia, Hyponatraemia (SAIDH), possible interaction with

cytochrome P450, Fluvoxamine and Citalopram may be more cardiotoxic in overdose

• MIRTAZEPINE: Limited data suggested is relatively safe
• MOCLOBEMIDE: Some case reports of hypertension exist
• MAOIs: Use with caution – potential for hypotension and hypertensive
• crisis. May cause arrhythmias and impair left ventricular function

MAINTENANCE THERAPY

Because of the high relapse rates of elderly people recovered from depression, maintenance therapy has been recommended for at least 6 months after an initial depressive episode. Patients who have had three or more depressive episodes should stay on therapy for life.

PSYCHOLOGICAL INTERVENTIONS

Cognitive behavioural therapy efficacious in some RCTs

Psychological treatment of late-life depression: meta-analysis of RCTs

• Cuijpers et al. (2006) Int J Geriatric Psychiatry, 21, 1139-49
• 25 studies included of which 17 compared a psychological

intervention to a control condition

• Psychological treatments had moderate to large effects on late

life depression (standardised effect size 0.72)

• Although many studies were suboptimal, psychological

treatments seem to help late–life depression – no differences in efficacy between types and format of psychological therapies were found.

SOCIAL INTERVENTIONS Re-housing, support, financial assistance

Multifaceted interventions (1)

• Multifaceted interventions need thorough prospective

evaluation.

• Receipt of a package of care from a psychogeriatric

team was 9 times more likely to be associated with recovery from depression than standard general practitioner care provided to a group of 69 depressed elderly people receiving home care in South London,

• UK. The result was not due to the simple prescribing
• f an antidepressant.

Banerjee et al. (1996) BMJ 313: 1058-1061

Multifaceted interventions (2)

An evaluation of a shared care intervention package that incorporated multidisciplinary collaboration, general practitioner training and resident education and activity programs reported more movement to be less depressed levels than in a control group of 220 depressed residents of a retirement complex in North Sydney.

Llewellyn-Jones et al. (1999) BMJ 319: 676-682

Multifaceted interventions (3)

The IMPACT Study When 906 patients aged 60+ were assigned a depression case manager for 12 months, 45% had 50% or greater reduction in depressive symptoms compared to 19% of 895 receiving “usual care”.

Unützer et al. (2002). JAMA 288: 2836-2845

Multifaceted interventions for late-life depression (4) Community-integrated home-based depression treatment in older adults: a randomized controlled trial

Ciechanowski et al., JAMA, 2004, 291: 1569-77

138 patients mean age 73, 79% female, with minor depression (49%) or dysthymia (51%) in Seattle, Washington, USA

• Assigned to usual care (66) or Program to Encourage Active Rewarding Lives

for Seniors (PEARLS) (72) which consisted of problem solving treatment, social and physical activation and potential advice to treating doctors regarding antidepressant treatments.

• At 12 months 43% vs 15% (OR 5.2, 95% CI 2.0-13.5) had at least 50%

reduction in depressive symptoms

• 36% vs 12% (5.0, 1.8-13.7) had complete remission of depression
• Intervention subjects had greater health related QOL improvements in

functional and emotional well-being

OUTCOME

Follow-up studies of up to 2 years duration find 22% of patients continuously depressed, 44% recover and remain well, 16% undergo at least

• ne depressive relapse and 23% have
• ther outcomes such as death or

dementia.

OUTCOME

Among cohorts with over 2 years of follow-up, 14% have continuous unremitting depression, 27% maintain long term remission after initial recovery, 33% have at least one relapse and 31% experience other outcomes

• Poor outcome in late life depression associates

inconsistently with physical illness severity, cognitive impairment and depression severity.

• The longer people have been ill before they get

treated the less likely they are to do well. Severe deep white matter hyperintensities on MRI are associated with poor long term outcomes.

• Severe intervening life events associate with

poorer outcomes.

• Other social variables have little apparent

impact.

OUTCOME IN GENERAL PRACTICE There is a dearth of studies examining the long term outcome of late life depression in primary care. A Dutch study using 14 GPs found 21/39 depressed elderly patients recovered after 18 months of standard care. See also IMPACT study

COMMUNITY OUTCOME

In 5 community studies depressed elderly individuals were identified in epidemiological surveys and then reviewed at a later date.

• 27% continuously depressed
• 34% recovered
• 31% had other outcomes
• Receipt of specific treatments was

unusual

TREATMENT RESISTANCE IN PATIENTS WITH DWMHs

• Patients with severe silent infarctions had longer hospital stays and poorer

response to antidepressants than those without infarction (Fujikawa et al., 1996)

• In 58 treatment resistant older patients with major depression lesions of

the basal ganglia, diabetes, lower mean blood pressure and hyperintensities in the reticular formation predicted 96% of patients with poor outcome (Simpson et al., 1997)

• Neuropsychological impairment suggestive of frontal sub-cortical

dysfunction more common in treatment resistant patients (Simpson et al., 1998)

• Hickie et al. (1995) found sub cortical HI on MRI was associated with poor

response to treatment in 39 elderly patients with severe depression

• Patients with severe white matter lesions have a faster time to relapse or

bad outcome (136 days) than those without severe lesions (315 days) (60 patients followed for 32 months by O’Brien et al., (1998))

SUICIDE

In most countries with available data, males over 75 are at a higher risk of suicide than other population groups. Up to 90% of these suicidal individuals are suffering from potentially treatable depressive disorder. Most consult health professionals within a few weeks before death.

BEST PRACTICE IN LATE LIFE DEPRESSION

• Evaluate older people for depressive

symptoms especially when in high risk groups.

• Antidepressants are helpful for the more

severe types of late life depression.

• Multifaceted interventions may be

promising.

• High relapse rates after initial recovery

point to the need for maintenance therapy