A century ago in Ireland, one individual in 20 was aged 65 years or over. Now, older people account for approximately 16% of the population, and by 2050, this is expected to rise to 25-30%. This demographic shift, with older people accounting for a greater proportion of the global population as well, is due to increased life expectancy and improvement in basic living conditions, as well as falling birth rates, particularly in western countries.¹

Depression is a frequently encountered condition in later life and its diagnosis can present particular challenges due to the possibility of its symptoms being atypical in nature. Having grown up with more stigmatised beliefs about mental illness and psychiatric treatments than subsequent generations, there is a reluctance, in older people, to voice concerns about one’s own mental health or to utilise mental health services. This poses a significant issue, for both themselves, and for their primary clinicians. Changes in the body and brain due to age, medical comorbidity or the need for multidrug regimens, can also lead to atypical manifestations of psychiatric illness, resulting in inaccurate or missed diagnoses.²

Presentation of late life depression 

A syndrome of motor symptoms, apathy and amotivation without depression with emphasis on somatic, as opposed to cognitive symptoms may be common.⁴ These notable differences to a classical depressive presentation among few others, as well as clinician reluctance to stigmatise patients with a psychiatric diagnosis, can result in under-diagnosis or a missed diagnosis in older people.⁵ Mild or non-specific symptoms of depression, a prescriber’s concern of side effects and interactions of medications and the incorrect perception that episodes of depression reactive to circumstances are not pathological can also delay diagnosis. There is a higher rate of delusional depression in older than younger depressives, and it is usually associated with hypochondriacal and nihilistic delusions, a high rate of delusional relapses and poorer response to antidepressant monotherapy. 

Subsyndromal depression is more common than major depression among older adults but has significant negative functional, social and medical consequences.⁴ Anxiety also may be a frequent presenting feature of late life depression and may manifest in patients seeking repeated investigation of somatic complaints with failure to accept appropriate reassurance. 

The impact of chronic medical illness on quality of life and functional ability is often apparent in the lives of older adults and relevant to psychiatric assessment and treatment.⁴ The reciprocal nature of the relationship between depression and physical illness results in depression and physical illness coexisting with and exacerbating each other, causing the symptoms of depression and the physical ailment to be more severe.⁶

Overlap with dementia

Dementia and depression have a complex relationship with several possible explanations, including depressive symptoms as prodromal to dementia, depression as a causative factor in dementia and shared risk factors between the two disorders.⁴ Impaired attention and processing speed associated with major depression may affect many cognitive domains. Severe depression may be related to pseudodementia, a syndrome in which depressive symptomatology produces cognitive impairment, causing significant disability and placing patients at risk of subsequent development of an actual dementia.⁷ Poor effort and excessive worry about cognitive symptoms may be clues to cognitive impairment related to depression, during cognitive testing.⁴

One important difference between Alzheimer’s disease and depression is the effectiveness of treatment. While Alzheimer’s drugs can only slow the progression of cognitive decline, medications to treat a diagnosed depression can improve a person’s quality of life dramatically.⁸ To detect depression in people who have Alzheimer’s disease, doctors must rely more heavily on non-verbal cues and caregiver reports. If a person with Alzheimer’s disease displays one of the first two symptoms in this list, along with at least two of the others for at least two weeks, he or she may be depressed:

• Significantly depressed mood – sad, hopeless, discouraged, tearful
• Reduced pleasure in or response to social contacts and usual activities
• Social isolation or withdrawal
• Eating too much or too little
• Sleeping too much or too little
• Agitation or lethargy
• Irritability
• Fatigue or loss of energy
• Feelings of worthlessness, hopelessness or inappropriate guilt
• Recurrent thoughts of death or suicide.⁸

Vascular depression is common and associated with executive dysfunction.⁴ This depression subtype is characterised by depression, apathy, cognitive decline, executive dysfunction, and psychomotor retardation and as such, resembles a subcortical dementia. Vascular depression is associated with poorer outcomes and an increased risk of relapse. Importantly, the degenerative changes in vascular depression may explain the decreased efficacy of antidepressants seen in some trials with elderly patients.⁶ A rating scale, eg. the Cornell Scale for Depression in Dementia may facilitate the assessment of the condition and estimate severity, thus providing a gauging point for treatment evaluation.

Psychological factors

Despite the prospect of bereavement or of physical illness, old age is not necessarily a time of despair and hopelessness. The resources of a lifetime of experience could help older adults to positively and constructively face the various changes that occur at this stage of their lives. Various factors influence a person’s ability to cope with the strain and challenges that come with stress. These include: past experience, personality and current resources, the meaning given to the present situation, their way of dealing with previous stresses and support from others. Particular stresses among older people are: widow(er)hood; moving house, especially moving into a nursing home; retirement; ill health, loss of independence. Psychologists have studied the adjustments that older people must make such as facing death, finding meaning in life despite loss of role, status or health, and facing regrets and disappointments. It is understandable how mental conflict in the face of these changes could result in significant anxiety and depression. Losses and personal disabilities may also trigger psychological struggles regarding one’s own mortality.⁴

Polypharmacy – ‘yet another tablet?’

Patients taking at least six medications daily on a chronic basis have an approximately double risk of drug-drug interactions than those taking three to five medications and six times higher risk than those taking zero to two medications.⁹ The high prevalence of polypharmacy with ageing may lead to an increased risk of inappropriate drug use, under-use of effective treatments, medication errors, poor adherence, drug-drug and drug-disease interactions and, most importantly, adverse drug reactions.10

Benzodiazepines are the most commonly used psychotropic drug in older people and can be very effective as antianxiety agents, but they should only be used for a time limited period. Adverse effects in this group include impaired cognition and gait and the development of tolerance dependence and subsequent withdrawal. Long acting benzodiazepines, eg. diazepam, chlordiazepoxide, flurazepam, nitrazepam, should usually be avoided in older people as they are likely to accumulate and therefore have an even greater potential for sedative effects and psychomotor impairment. 

It is appropriate to try and taper and discontinue benzodiazepines even in cases where older people have been taking them on a long term basis; however complete withdrawal may be challenging due to physical or psychological dependence. Best practice is through discussion and psychoeducation to determine if the patient will agree to a slow taper and possible discontinuation of the medication. Over-prescription of benzodiazepines may mask depressive symptoms and delay proper and correct pharmacological antidepressant intervention for an underlying depression. Polypharmacy may also be contributed to by excessive ingestion of alcohol and over-the-counter drugs, often with a desire to self-medicate and obtain symptom relief. Other medical drugs that can mimic or even cause depression in older people include B blockers, steroids and digoxin.

With polypharmacy also comes the risk of non-compliance with the prescribed medications. This may be due to the complexity of medication regimen, cost, side effects, cognitive impairment or a preference for different treatment. 

Treatment and therapy

The modern management of major depressive disorder in the older-aged population is divided into three phases, namely:

• Acute treatment phase to bring about recovery and remission of symptoms
• Continuation phase to prevent a relapse
• Maintenance phase to prevent a recurrence.

Social

A balanced biopsychosocial perspective remains crucial as well. Psychiatric assessment and care of older adults requires careful attention to social networks and often includes family members in the assessment and treatment of the older adult (with consideration for struggles for autonomy and role reversals).⁴ Family members and other caregivers are crucial to understanding the social context and can assist with medication adherence, transportation to appointments, and social support. Interventions may include referrals for home help and meals on wheels, referral to a day centre or support group and helping people to check on their welfare entitlements. These simple initiatives, although seemingly minor, can make a big impact on depressive disorder.

Psychological

Where poor housing, social isolation or bereavement have contributed to the development of depression, a complete and lasting recovery is unlikely until these factors have been addressed in their own right. Bereavement counselling and family therapy are interventions that can yield positive results when appropriately targeted. Psychotherapy is relatively underprescribed, yet extremely useful for the treatment of depression in older people. The evidence based approaches that provide notable results include cognitive behavioural therapy, interpersonal therapy, problem solving therapy and psychodynamic psychotherapy. Group therapy may also be useful for older individuals who need help to develop their social skills, or who do not respond to individual therapy. Listening to their peers can help to normalise late-life struggles, and facilitates ‘venting’ otherwise difficult to express feelings.¹¹

Pharmacotherapy

Pharmacotherapy has become a cornerstone of management of depression in later life. For this special patient population, it is key to select medications tailored to patient-specific comorbid medical illnesses, past treatments, drug-drug interactions, predictors of adherence, cognitive dysfunction or vulnerabilities (such as risk of falls). A review by Beyer concluded that all classes of antidepressants, including the SSRIs, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs), have similar efficacies.¹² However, pharmacologic treatment can be more personalised, according to the comorbid psychiatric illness. For example when an SSRI is ineffective, one may consider a switch to venlafaxine if anxiety is prominent, bupropion when apathy is more notable, mirtazapine for patients with insomnia and anxiety, or nortriptyline if the depression is melancholic in nature. Relapse is more common in older patients, so successful treatment with an antidepressant should be continued for one to three years after remission, and longer (up to lifelong treatment) in high risk patients.¹² Psychotropic medications are likely to demonstrate anticholinergic properties, associated with low cognitive performance and so, longitudinal monitoring should also address cognitive decline.¹³

Treatment-resistant depression

When starting pharmacotherapy, it is advisable to prescribe low doses and go slowly, monitoring adherence and side effects closely.

If there is no response by four to six weeks and the medication is well tolerated, reassess the dose and consider an increase. It would be helpful to keep in mind factors that would affect treatment results, including:

• Adequacy of prior treatment – duration of treatment and dosage of medication
• Behavioural/environmental factors – personality disorder, psychosocial stressors
• Compliance – patient education, treatment intolerance.
• Diagnosis – missed medical diagnosis or adverse medication effect, missed psychiatric diagnosis.

If there is no sign of response within another week or two, change to another antidepressant. This is simpler, less costly, avoids drug/drug interactions, reduces side effects, introduces a ‘different mechanism’ and can be done in a clinic setting. If there is a partial response at four to six weeks, the trial should be extended to 12 weeks, during which time the decision can be made to either increase the dose, augment with another agent, or switch to a new agent in a different antidepressant family.¹⁴

Patients with residual depressive symptoms despite long-term antidepressant therapy are at significant risk of relapse and may benefit from the addition of such atypical antipsychotics as olanzapine, aripiprazole, quetiapine or lithium. The implementation can be done at a faster rate but there are risks of drug/drug interaction and side effects.

Electroconvulsive therapy is an underused modality, but is especially suitable with antidepressant intolerance or non-response, prior positive response to ECT, delusions, catatonia, mania, and emergency. High response rates have been documented.¹⁵

Careful assessment

The stigma of mental illness associated with ageing, medical comorbidity, unique psychosocial stressors, and the importance of social support and extended involvement of family call for a broad system based approach to the psychiatric care of older adults. Major depressive disorder adversely affects all aspects of life but because of cognitive dysfunction, exhaustion, and other age-related symptoms, it may not be properly diagnosed initially or it may be mistaken for normal responses to end-of-life issues such as infirmity and mortality.

A number of biological, clinical, and psychosocial factors influence treatment response. Suicidal ideation is common in older adults with depression, and the risk of suicide should be carefully assessed and managed accordingly. Predictors of poor outcome would include symptom severity, comorbid dysthymia, vascular damage, and poor social support. Diminished adherence to medication regimens, in patients with impaired cognition may also have a similar prognosis. For optimal treatment, late-life major depressive disorder should be approached as a condition with a clinical profile quite markedly separate from that observed in younger patients. It is critical to develop a treatment plan in collaboration with the patient. As a physician, our duty to our older aged patients requires us to remain hopeful and persevering, quintessentially keeping in mind that depression is not a conclusive consequence of old age, but that with appropriate treatment, social support and close monitoring, it can be properly managed and, quite frequently, placed into remission.

References

1. Cohen JE. Human population: the next half-century. Science 2003;302(5648):1172–5.
2. Bair BD: Frequently missed diagnosis in geriatric psychiatry. Psychiatry Clin North Am 1998; 21:941 – 971, viii
3. Depression Without Sadness: Alternative Presentations of Depression in Late Life JOSEPH J. GALLO, M.D., M.P.H., University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania PETER V. RABINS, M.D., M.P.H., Johns Hopkins University School of Medicine, Baltimore, Maryland, Am Fam Physician. 1999 Sep 1;60(3):820-826.
4. www.focus.psychiatryonline.org Winter 2009, Vol VII, No. 1, Psychiatric Assessment and Diagnosis in Older Adults
5. Piven M. Detection of depression in the cognitively intact older adult. Iowa city, IA: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core; 2005.
6. Alexopoulos GS, et al. Am J Psychiatry. 1993;150:1693-1699.
7. National Institute of Mental Health. Depression. Bethesda, MD: National Institute of Mental Health, US Department of Health and Human Services; 2008. NIH publication 08-3561.
8. http://www.mayoclinic.com/health/alzheimers/HQ00212
9. Nobili A, et al. J Clin Pharm Ther. 2009;34:377-386.
10. Bressler R, Bahal JJ. Principles of drug therapy for elderly patients. Mayo Clin Proc 2003;78(12):1564–77.
11. Agronin M. Curr Psychiatry Rep. 2009;11:27-32.
12. Beyer JL. Ann Clin Psychiatry. 2007;19:221-238.
13. Dillon C, et al. Neuropsychiatric Dis Treat. 2009;5:517-526.
14. Driscoll HC, et al. Drugs Aging. 2007;24:801-814
15. http://www.aetna.com/cpb/medical/data/400_499/0445.html