Late-life Depression (Geriatric Depression)

Primer

Geriatric Depression (also known as Late-Life Depression, or LLD) is a subtype of depression characterized by changes in mood, lack of pleasure, and often somatic symptoms in older adults. It is one of the major geriatric giants. It is most commonly defined as depression occurring in adults age 60 and over.[1]

Epidemiology
  • The community prevalence rates of late-life depression is 11.2% for combined symptoms of major and minor depression.[2]
Prognosis
  • Compared to individuals with an earlier age-of-onset of depression, late-onset depression has a worse prognosis, a more chronic course, and generally a higher relapse rate.[3]
  • There is thought to be an association between vascular disease and depression, and that depression in late-life is a prodrome (warning sign) for neurodegenerative disorders.
Comorbidity
  • Late-life depression is complicated by higher rates of medical comorbidity, cognitive impairment, and mortality.[4]
Risk Factors
  • Medical comorbidity, cardiovascular disease, low education, and increased age are risk factors.[5]

Diagnosis

  • Generally, the diagnosis of late life depression can be made using DSM 5 criteria for major depressive disorder.
    • However, older adults are less likely to directly endorse being “depressed”, guilt, or hopelessness
    • More commonly, individuals will endorse anhedonia, cognitive concerns (poor concentration, memory, and decision-making capacity), and somatic complaints.[6]
  • Awareness of other medical causes and psychosocial causes must be thoroughly considered due to higher rates of medical comorbidities.
    • For example, the criterion for “markedly diminished interest or pleasure” may overlap with or be confused with the apathy due to dementia or an underlying neurological disease.
    • Psychomotor slowing, sleep changes, fatigue, low energy, weight loss and/or poor appetite can also be caused by an underlying medical illness, major neurocognitive disorder, substances (such as alcohol or opioids).
    • Feelings of worthlessness and suicidal ideation can also be due to end-of-life issues rather than a depressive episode.[7]

Assessment

A complete assessment for late-life depression requires:

  • Reviewing the diagnostic criteria for late-life depression
  • Reviewing current medications, allergies, and substance use
  • Reviewing current stresses and life situation
  • Assessing level of functioning/disability
  • Considering support system, family situation, and personal strengths
  • Cognitive testing
  • Neurological exam and physical exam if applicable
  • Ordering laboratory investigations to identify any medical problems that could contribute to or mimic depressive symptoms (e.g. - hypothyroidism, anemia)

Suicide

  • Older adults have one of the highest suicide rates in North America, largely due to the risk in older white males (higher intent and likelihood to complete suicide).[8]

Screening and Rating Scales

Geriatric Depression Scales

Name Rater Description Download
Geriatric Depression Scale (GDS) Clinician/Patient 30-question (15-questions for the short version) from a clinician scoring or self-report assessment with “yes” or “no” answers. 1 point assigned to each positive answer (See author's website for more details). • Short-form (15 questions)
• Long-form (30 questions)

Pathophysiology

Vascular Depression Hypothesis

  • The vascular depression hypothesis suggests that cerebrovascular disease predisposes, precipitates, or perpetuates depressive symptoms in late-life. Vascular disease (e.g. - atherosclerosis, strokes, white matter disease) are thought to affect fronto-striatal circuitry, resulting in executive dysfunction, depression, and cognitive impairment.[9]

Differential Diagnosis

Dementia, Depression, or Delirium?

  • In the geriatric population, it is important to differentiate between delirium, dementia, and depression, which can be difficult to distinguish.[10][11][12] The prevalence of delirium superimposed on dementia ranges anywhere from 22% to 89% of hospitalized and community populations aged 65 and older with dementia.
  • The negative outcomes of these co-occurring conditions include accelerated and long-term cognitive, functional decline, institutionalization, re-hospitalization, and increased mortality.[13]

A Comparison of Delirium, Dementia, and Depression

Adapted from: Fong, T., et al. Delirium in elderly adults: diagnosis, prevention and treatment. Nature Reviews Neurology 5.4 (2009): 210.
Delirium Dementia Depression
Cardinal feature Confusion and Inattention Memory loss Sadness, anhedonia
Onset Acute or subacute Insidious Slow
Course Fluctuating, often worse at night Chronic, progressive (but stable over the course of a day) Single or recurrent episodes; can be chronic
Duration Hours to months Months to years Weeks to years
Level of Conciousness (LOC) Impaired, fluctuates Normal in early stages Normal
Attention (i.e. - able to focus on tasks) Poor Normal (except in
late stages) 		May be impaired
Orientation (i.e. - date, location) Fluctuates Poor Normal
Memory (i.e. - short-term memory) Poor Poor May be impaired
Hallucinations Common (visual) Rare, except in
late stages (and depends on type of dementia) 		Not usually (only if psychotic depression)
Delusions Fleeting, non-systematized Often absent Not usually (only if psychotic depression)
Psychomotor Increased (hyperactive) or reduced (hypoactive) No Yes
Reversibility Yes Rarely Yes
EEG Findings Moderate to severe background slowing Normal or mild diffuse slowing Normal (usually)

Psychotic Depression

Depression in Dementia

  • Antidepressants do not work well in the treatment of depression in individuals with dementia.[14][15]
    • Rigorous randomized clinical trials have not shown benefit (mirtazapine, sertraline) over placebo.[16]
    • Therefore, guidelines do not suggest the routine treatment of depression and anxiety with antidepressants.

Investigations

  • Routine investigations should be done including: CBC, electrolytes, extended electrolytes (calcium, magnesium, phosphate), TSH, and vitamin B12

Vitamin B12 Deficiency

  • Depression, dementia, and cognitive impairment are often associated with vitamin B12 (cobalamin) deficiency and folate deficiency, especially in the elderly. Although laboratory norms and ranges may show that a serum vitamin B12 level between 200 pg/mL and 900 pg/mL is considered normal, a minimum level of 300 to 350 pg/mL is desirable in the elderly.[17]

Physical Exam

  • A neurological exam is recommended if there are symptoms such as tremors or falls.

Treatment

Psychotherapy

Pharmacotherapy

  • Bupropion, mirtazapine, moclobemide, and venlafaxine are all relatively safe in the elderly. They have lower anticholinergic effects compared to older antidepressants like tricyclic antidepressants. This also makes them relatively well-tolerated by patients with cardiovascular disease.
  • There have been paradoxical findings in antidepressants studies in late-life depression, showing that commonly prescribed medications such as escitalopram and citalopram do not outperform placebo (while more anticholinergic medication such as paroxetine did).[19]
    • One reason for these findings is that depression in the elderly is best conceptualized as a heterogenous syndrome, representing “true biological depression”, and other mimics, such as early signs of dementia or vascular depression.
    • Many clinicians opt to prescribe medications with lower anticholinergic burden to minimize delirium and cognitive impairment risk. Other considerations include medications with a lower risk for falls.
  • Generally speaking however, in clinical studies, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOis) have been shown to be the most efficacious in the treatment of geriatric depression.[20]
  • Lithium augmentation for treatment-refractory depression also has evidence.[22]

Pharmacotherapy for Geriatric Depression

Lam, R. W. et al. (2017). Response to Letter Regarding CANMAT Recommendations for the Pharmacological Treatment of Late-life Depression. The Canadian Journal of Psychiatry, 62(5), 353-354.*
1st Step
(use one or more agents in sequence) 		Monotherapy: duloxetine, mirtazapine, sertraline, venlafaxine, vortioxetine, citalopram, desvenlafaxine, escitalopram
2nd Step
(if multiple 1st-step treatments are not effective or not indicated) 		Switch to: nortriptyline, fluoxetine, moclobemide, paroxetine, phenelzine, quetiapine, trazodone, bupropion
Or combine with: aripiprazole (2.5 to 15 mg)[23], methylphenidate, lithium
3rd Step
(if multiple 1st- and 2nd-step treatments are not effective or not indicated) 		Switch to: amitriptyline, imipramine
Or combine with: an SSRI or SNRI with bupropion
* = Note that the originally published CANMAT 2016 Guidelines 'Section 6. Special populations: Youth, women, and the elderly.' had several typographical errors and errata. This table references the corrected response letter with an updated table. See reference above for details.

Pharmacotherapy Initiation and Monitoring

  • A “start low, go slow, but keeping going” approach to medications is recommended.[24]
    • It appears that older adults require longer periods of antidepressant trials (between 10 to 12 weeks) compared to younger adults
  • Prescribers need to be especially aware of the geriatric giants, pharmacokinetic and pharmacodynamic changes in old age, increased risk for drug-drug interactions, and adverse drug events.
    • For example, older adults will have greater retention of lipid-soluble drugs due to increased body fat, have slower metabolism and excretion, and lower rates of absorption.
    • Common side effects and adverse events in the elderly include hyponatremia, QTc prolongation, anticholinergic burden, falls, and gastrointestinal bleeding).[25]

Monitor for Hyponatremia!

Monitor for electrolytes within one month of starting an SSRI. This is especially important in individuals taking other medications, such as diuretics, which can cause hyponatremia.

ECT

  • ECT is a safe and effective treatment for depression in older adults.
  • Older adults who receive ECT have a lower mortality rate compared to other depression treatments (i.e. - antidepressants)[26][27]
  • Right unilateral, ultrabrief pulse ECT (average of 7 treatments of ECT), when combined with venlafaxine, can be a rapidly acting and effective treatment in depressed geriatric patients. There very good safety and tolerability when this combination therapy is used.[28]

Guidelines

Geriatric Depression Guidelines

Guideline Location Year PDF Website
Canadian Network for Mood and Anxiety Treatments (CANMAT) Canada 2016 - • Original: Link
• Correction: Link
Canadian Coalition for Seniors' Mental Health (CCSMH) Canada 2021 Link CCSMH Depression

Resources

For Patients
For Providers
Articles
Research

References

1) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
2) Koenig, H. G., Meador, K. G., Cohen, H. J., & Blazer, D. G. (1988). Self‐rated depression scales and screening for major depression in the older hospitalized patient with medical illness. Journal of the American Geriatrics Society, 36(8), 699-706.
3) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
4) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
5) Sözeri-Varma, G. (2012). Depression in the elderly: clinical features and risk factors. Aging and disease, 3(6), 465.
6) Fiske, A., Wetherell, J. L., & Gatz, M. (2009). Depression in older adults. Annual review of clinical psychology, 5, 363-389.
7) Blackburn, P., Wilkins-Ho, M., & Wiese, B. (2017). Depression in older adults: Diagnosis and management. BC Medical Journal, 59, 171-177.
8) Szanto, K., Gildengers, A., Mulsant, B. H., Brown, G., Alexopoulos, G. S., & Reynolds, C. F. (2002). Identification of suicidal ideation and prevention of suicidal behaviour in the elderly. Drugs & Aging, 19(1), 11-24.
9) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
10) Brown, T. M., & Boyle, M. F. (2002). Delirium. Bmj, 325(7365), 644-647.
11) Fong, T. G., Davis, D., Growdon, M. E., Albuquerque, A., & Inouye, S. K. (2015). The interface of delirium and dementia in older persons. The Lancet. Neurology, 14(8), 823.
12) Fong, T. G., Tulebaev, S. R., & Inouye, S. K. (2009). Delirium in elderly adults: diagnosis, prevention and treatment. Nature reviews neurology, 5(4), 210.
13) Fick, D. M., Agostini, J. V., & Inouye, S. K. (2002). Delirium superimposed on dementia: a systematic review. Journal of the American Geriatrics Society, 50(10), 1723-1732.
14) Rosenberg, P. B., Martin, B. K., Frangakis, C., Mintzer, J. E., Weintraub, D., Porsteinsson, A. P., ... & DIADS-2 Research Group. (2010). Sertraline for the treatment of depression in Alzheimer disease. The American Journal of Geriatric Psychiatry, 18(2), 136-145.
15) Dudas, R., Malouf, R., McCleery, J., & Dening, T. (2018). Antidepressants for treating depression in dementia. Cochrane Database of Systematic Reviews, (8).
16) Banerjee, S., Hellier, J., Dewey, M., Romeo, R., Ballard, C., Baldwin, R., ... & Burns, A. (2011). Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. The Lancet, 378(9789), 403-411.
17) Hanna, S., Lachover, L., & Rajarethinam, R. P. (2009). Vitamin B12 deficiency and depression in the elderly: review and case report. Primary care companion to the Journal of clinical psychiatry, 11(5), 269.
18) Kiosses, D. N., Leon, A. C., & Areán, P. A. (2011). Psychosocial interventions for late-life major depression: evidence-based treatments, predictors of treatment outcomes, and moderators of treatment effects. Psychiatric Clinics, 34(2), 377-401.
19) Alexopoulos, G. S. (2011). Pharmacotherapy for late-life depression. The Journal of clinical psychiatry, 72(1), e04.
20) Mittmann, N., Herrmann, N., Shulman, K. I., Silver, I. L., Busto, U. E., Borden, E. K., ... & Shear, N. H. (1999). The effectiveness of antidepressants in elderly depressed outpatients: a prospective case series study. The Journal of clinical psychiatry, 60(10), 690-697.
21) Mittmann, N., Herrmann, N., Shulman, K. I., Silver, I. L., Busto, U. E., Borden, E. K., ... & Shear, N. H. (1999). The effectiveness of antidepressants in elderly depressed outpatients: a prospective case series study. The Journal of clinical psychiatry, 60(10), 690-697.
22) Kok, R. M., Vink, D., Heeren, T. J., & Nolen, W. A. (2007). Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized, controlled trial. Journal of Clinical Psychiatry, 68(8), 1177-1185.
23) Lenze, E. J., Mulsant, B. H., Roose, S. P., Lavretsky, H., Reynolds III, C. F., Blumberger, D. M., ... & Karp, J. F. (2023). Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. New England Journal of Medicine.
24) MacQueen, G. M., Frey, B. N., Ismail, Z., Jaworska, N., Steiner, M., Lieshout, R. J., Kennedy, S. H., Lam, R. W., Milev, R. V., Parikh, S. V., Ravindran, A. V., & CANMAT Depression Work Group (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Canadian journal of psychiatry, 61(9), 588–603.
25) Sobieraj, D. M., Martinez, B. K., Hernandez, A. V., Coleman, C. I., Ross, J. S., Berg, K. M., ... & Baker, W. L. (2019). Adverse effects of pharmacologic treatments of major depression in older adults. Journal of the American Geriatrics Society, 67(8), 1571-1581.
26) Kerner, N., & Prudic, J. (2014). Current electroconvulsive therapy practice and research in the geriatric population. Neuropsychiatry, 4(1), 33–54.
27) Avery, D., & Winokur, G. (1976). Mortality in depressed patients treated with electroconvulsive therapy and antidepressants. Archives of general psychiatry, 33(9), 1029-1037.
28) Kellner, C. H., Husain, M. M., Knapp, R. G., McCall, W. V., Petrides, G., Rudorfer, M. V., ... & Prudic, J. (2016). Right unilateral ultrabrief pulse ECT in geriatric depression: phase 1 of the PRIDE study. American Journal of Psychiatry, 173(11), 1101-1109.