GERIATRIC MOOD DISORDER: DEPRESSION (20-Mark Answer)

1. Introduction and Significance

2. Epidemiology

• The National Comorbidity Survey Replication found overall MDD prevalence among persons aged 65+ was 1.5% in women and 0.2% in men (overall ~1%) - approximately one-fourth of that in younger adults.
• MDD affects 1-5% of community-dwelling older adults and 6.5-9% of patients in primary care clinics.
• When combining symptoms of major/minor depression with reported treatment, the cumulative prevalence reaches 11.19%, with similar rates in men (10.19%) and women (11.44%).
• 15-36% of community-dwelling older adults endorse subthreshold but clinically significant depressive symptoms.
• Rates are highest in nursing home/institutional settings and among the medically ill.
• Longitudinal studies of 1-6 years suggest 7-30% of geriatric patients have chronic major depression; if partially remitted subjects are included, the chronicity rate reaches 40%.

3. Risk Factors

Biological Risk Factors

• Advanced age, female sex
• Medical comorbidities (cardiovascular disease, cerebrovascular disease, diabetes, cancer, Parkinson disease, thyroid disease)
• Prior depressive episodes, family history
• Neurobiological changes: white matter hyperintensities, reduced hippocampal volume, frontal-subcortical circuit dysfunction
• Sleep disorders, chronic pain

Psychosocial Risk Factors

• Social isolation and loneliness - strongly linked to depressed mood, decreased well-being, and higher mortality
• Bereavement (loss of spouse, family members)
• Loss of independence and functional decline
• Caregiver stress
• Low socioeconomic status
• Racial and ethnic minority status (greater burden of unmet mental health needs)

4. Clinical Features (Presentation in Older Adults)

• Somatic emphasis: More likely to describe somatic complaints as primary - sleep problems, fatigue, decreased appetite, weight loss, GI distress, pain, hypochondriasis
• Psychomotor changes: Slowing or agitation are prominent
• Cognitive symptoms: Memory deficits, poor concentration, reduced processing speed, executive dysfunction - can resemble dementia ("pseudodementia")
• Anhedonia without sadness: Older adults often experience depression as loss of interest rather than explicit depressed mood
• Irritability: May substitute for classical sadness
• Absence of "typical" depressive complaint: Rarely say "I feel depressed"

Subtypes in Geriatric Depression

1. Psychotic Depression: Occurs in 20-45% of hospitalized depressed older adults and 3.6% in community. Features delusions (guilt, hypochondriasis, nihilism, persecution) more than hallucinations. Worse prognosis, higher severity, malnutrition, dehydration, and cognitive deficits common.
2. Vascular Depression: Related to cerebrovascular disease and white matter changes. Features prominent cognitive impairment, lack of family history, psychomotor slowing, and executive dysfunction.
3. Depression with Reversible Dementia (Pseudodementia): Depression-induced cognitive syndrome that improves after treatment but carries ~20% per year risk of developing irreversible dementia on follow-up.
4. Minor/Subsyndromal Depression: Very common in older adults; associated with significant disability, increased morbidity/mortality, and elevated risk (~fivefold) for developing MDD.

5. Neurobiology / Pathophysiology

Vascular Hypothesis

Inflammation Hypothesis

• Aging causes a chronic proinflammatory state (neuroinflammation)
• Elevated peripheral cytokines (IL-6, TNF-alpha, CRP) are associated with depressive symptoms in older adults
• Cytokines induce indoleamine 2,3-dioxygenase - this enzyme reduces serotonin production
• Cytokines also dysregulate the glutamate system, promote excitotoxicity, and decrease production of neurotrophic factors
• A meta-analysis of 82 studies confirmed peripheral elevations of IL-6, TNF-alpha, IL-10, and other cytokines in MDD vs. controls

HPA Axis Dysregulation

• Aging is associated with reduced negative feedback of the HPA axis
• Elevated cortisol causes hippocampal neuronal damage and reduced neuroplasticity
• Glucocorticoid resistance in monocytes promoted by inflammatory cytokines

Monoamine Changes

• Reduced serotonin, norepinephrine, and dopamine transmission
• Reduced 5-HTTLPR allele function linked to both lower remission rates AND more microstructural white matter abnormalities in frontolimbic areas

Relationship with Dementia

• A history of depression doubles the risk of developing dementia in late life (meta-analysis)
• Amyloid-beta (Abeta) burden and regional tau burden are associated with worsening depressive symptoms even in cognitively normal older adults
• Long-term antidepressants delay the conversion of mild neurocognitive disorder to Alzheimer dementia

6. Comorbidities

• Depression in cancer: Among the highest rates of completed suicide; depression decreases treatment adherence, increases hospital stay
• Depression in dementia: Prevalence above 30% in mild NCD; 5-48% in Alzheimer disease. Depression may be an early symptom, risk factor, or prodrome of dementia
• Depression in Parkinson disease: Up to 50% prevalence
• Depression in cerebrovascular disease: ~25% prevalence
• Suicide: Older adults (especially white males aged >85) have the highest rates of completed suicide; geriatric patients with cancer have some of the highest rates of completed suicide

7. Assessment and Diagnosis

Diagnostic Criteria

Assessment Tools

• Geriatric Depression Scale (GDS): 30-item or 15-item version; validated for older adults; avoids somatic items
• PHQ-9: Commonly used in primary care
• Hamilton Depression Rating Scale (HDRS/HAM-D)
• Cornell Scale for Depression in Dementia: Used when cognitive impairment is present

Assessment Domain Checklist

1. Full psychiatric evaluation (symptom severity, psychosis, suicidality)
2. Medical and neurologic evaluation
3. Functional status (ADLs, IADLs)
4. Cognitive screening
5. Social support and psychosocial stressors
6. Medication review (drugs causing depression: corticosteroids, beta-blockers, interferon, reserpine)
7. Labs: TFTs, CBC, metabolic panel, B12/folate, VDRL

8. Treatment

Goals of Treatment

1. Remission of depression
2. Reduction in risk of relapse and recurrence
3. Improvement of cognitive and functional status
4. Development of coping skills and provision of support for psychosocial adversity

A. Pharmacotherapy

SSRIs (First-line)

• Sertraline: Well-tolerated; approved for geriatric depression; limited CYP interactions
• Escitalopram: Minimal drug-drug interactions; effective in late-life depression
• Citalopram: Effective but dose-limited to 20 mg/day in older adults due to QTc prolongation risk (FDA black box)
• Fluoxetine: Long half-life makes it problematic in older adults; avoid

Newer SSRIs/Multimodal

• Vortioxetine: Serotonin 1A agonist + 5-HT3 antagonist + 1D and 7 antagonist + 1B partial agonist. Effective in late-life depression; may improve cognitive domains including memory and executive dysfunction. Dose: 5-20 mg/day; metabolized by CYP2D6
• Vilazodone: SRI + 5-HT1A partial agonist. Starting dose 10 mg/day, target 20-40 mg/day

SNRIs

• Venlafaxine XR: High remission rates; effective for hospitalized and treatment-resistant patients; also for comorbid chronic pain. Dose 112.5-225 mg/day for older adults. Monitor blood pressure (can increase BP at >225 mg). Short half-life - abrupt discontinuation causes withdrawal
• Duloxetine: Balanced serotonergic/noradrenergic action; effective for depression and comorbid pain. Start 30 mg/day x 1 week, then increase to 60 mg/day
• Levomilnacipran: Higher selectivity for norepinephrine; some evidence of greater antidepressant response in those over age 60; caution - may be less well tolerated in older adults. Dose: 40-120 mg/day; metabolized by CYP3A4

TCAs

• Nortriptyline and desipramine (secondary amines) are preferred over tertiary amines (amitriptyline, imipramine) due to better tolerability
• Monitor for anticholinergic effects (urinary retention, constipation, confusion, dry mouth), orthostatic hypotension, sedation, cardiac conduction effects (QTc prolongation)

MAOIs

• Reserved for treatment-resistant depression
• Dietary restrictions and drug interactions limit use in older adults

Augmentation Strategies

• Lithium augmentation: effective but narrow therapeutic window; monitor levels, renal function, thyroid function
• Atypical antipsychotics: aripiprazole, quetiapine for psychotic depression or augmentation
• Methylphenidate: may be used in medically ill, apathetic older adults (off-label)

ECT (Electroconvulsive Therapy)

• Highly effective, especially for:
  • Severe psychotic depression
  • Treatment-resistant depression
  • Severely suicidal patients requiring rapid response
  • Patients unable to tolerate medication
• Very safe in elderly when medically optimized
• Main side effect: transient post-ictal confusion and memory impairment (usually reversible)

B. Psychotherapy

1. Cognitive Behavioral Therapy (CBT): Well-established; addresses cognitive distortions and maladaptive behavior. Also delivered via telehealth. Useful even in the context of mild cognitive impairment
2. Problem-Solving Therapy (PST): Particularly effective in older adults with executive dysfunction and disability-related depression in primary care settings
3. Interpersonal Psychotherapy (IPT): Focuses on grief, role transitions, and interpersonal disputes - all highly relevant in late life
4. Supportive Psychotherapy
5. Life Review/Reminiscence Therapy: Unique to geriatric population; uses structured reflection on past experiences
6. Behavioral Activation: Increases engagement with rewarding activities; appropriate for cognitively impaired patients

C. Collaborative Care Model

9. Course and Prognosis

• 13-19% relapse/recurrence rate at 1 year in naturalistic studies
• 15% relapse rate with controlled antidepressant treatment (better than younger adults' 34%)
• With 3-6 year follow-up, recurrence rate rises to 38%
• 20-year follow-up in mixed-age patients: 95% had a recurrence
• Predictors of chronicity: Long current/prior episodes, medical comorbidity, high severity, nonmelancholic/delusional presentation
• Predictors of relapse/recurrence: Frequent prior episodes, late age of onset, history of dysthymia, intercurrent medical illness, greater functional impairment, external locus of control
• Depressed older adults with concurrent mild cognitive impairment: ~40% progress to AD within 27 months

GERIATRIC PSYCHOSIS (20-Mark Answer)

1. Introduction and Classification

1. Early-Onset Schizophrenia (EOS) - onset before age 40, now in older adults
2. Late-Onset Schizophrenia (LOS) - onset after age 40 (up to 60)
3. Very Late-Onset Schizophrenia-Like Psychosis (VLOS) - onset after age 60
4. Delusional Disorder
5. Psychosis in Dementia (most common cause in the elderly)
6. Psychotic Depression
7. Secondary/Organic Psychoses - from medical illness, medications, substance use

2. Epidemiology

• A review of schizophrenia in later life found that slightly less than one-quarter of patients with schizophrenia had onset after age 40 - 13% in the fifth decade, 7% in the sixth decade, and 3% in later decades
• A Dutch case-register study found a 1-year prevalence of 0.55% for schizophrenia in persons over 59 years; 64% had EOS and 35% had LOS
• VLOS is rare: annual incidence of 27/100,000 men and 48/100,000 women
• LOS and VLOS affect women 2-10 times more often than men - in contrast to EOS which is more common in men

3. Classification: EOS vs. LOS vs. VLOS

4. Etiology and Pathophysiology

LOS

• Considered a neurodevelopmental disorder - differences from EOS are more of degree than kind (International LOS Group consensus)
• Estrogen hypothesis: Women are protected by estrogen-mediated dopaminergic inhibition in younger years; relative estrogen deficiency with menopause increases LOS risk. Treatment with estrogen in postmenopausal women with schizophrenia has shown symptom improvement.
• Neuroimaging differences found in 8 of 10 studies comparing EOS and LOS (though inconsistent)
• Raised CRP concentrations found in LOS and VLOS (inflammatory component)

VLOS

• May have a neurodegenerative component - includes more brain abnormalities and neuropsychological deficits
• Cognitive dysfunction affects frontal-subcortical domains - memory relates to learning new information but retention is unaffected (contrasts with cortical dementias like Alzheimer disease, where retention is impaired)
• Genetic factors have NOT been implicated in VLOS

Delusional Disorder

• Presents in middle or late life
• Non-bizarre delusions involving real-life situations (being poisoned, having a disease, spousal infidelity)
• No prominent hallucinations, no functional deterioration outside delusion area
• High psychiatric comorbidity, especially depressive disorders

Psychosis in Dementia

• Most common cause of new-onset psychosis in elderly
• Alzheimer disease and vascular dementia are the most common types
• Features: delusions (usually persecutory), visual hallucinations, misidentification syndromes, agitation, aggression
• These neuropsychiatric symptoms cause early institutionalization, increased caregiver burden, and higher healthcare costs

5. Clinical Features

EOS in Older Adults (Chronic Schizophrenia)

• Older patients typically have fewer and less severe positive symptoms than younger patients
• Negative symptoms (flat affect, alogia, avolition) tend to persist into late life
• Cognitive deficits are present but generally remain stable over time (apart from normal aging)
• Higher mortality from suicide; rates comparable to younger schizophrenia patients

LOS Distinctive Features

• Better premorbid functioning - successful occupations, marital histories
• Less severe neurocognitive impairment than EOS
• Respond well to lower antipsychotic doses
• Social isolation greater than general population despite higher marriage rates

VLOS Distinctive Features

• Partition delusions (high prevalence): conviction that people, objects, or radiation can pass through walls, windows, doors
• Multi-sensory hallucinations: auditory, visual, tactile, olfactory
• Formal thought disorders and negative symptoms are infrequent - key point of debate for whether VLOS is truly schizophrenia
• Mood disruption often occurs
• Patients tend to be agitated and combative about paranoid experiences

6. Differential Diagnosis of Psychosis in Elderly

7. Role of Sensory Impairment

8. Course and Prognosis

• LOS course: Often chronic but may be interrupted by partial remissions and exacerbations
• Cognitive deficits in LOS remain relatively stable over time (unlike dementia, which is progressive)
• Overall prognosis of LOS may be better than EOS - patients respond to lower antipsychotic doses
• Mortality rates, especially from suicide, exceed the general population and are probably comparable to EOS
• VLOS: Heterogeneous outcome; some develop dementia with time; a long cited Australian study found conversion to dementia in 9 of 19 subjects over 5 years, though criticized for possibly including early-stage dementia patients

9. Assessment

History

• Age of onset, duration, course of symptoms
• Premorbid personality and functioning
• Medical history, medications (especially new drugs)
• Substance use history
• Family psychiatric history

Mental State Examination

• Positive symptoms: nature of delusions, hallucinations (type, modality)
• Negative symptoms
• Cognitive assessment (MMSE, MoCA) - mandatory in geriatric psychosis
• Affective symptoms (rule out psychotic depression, bipolar with psychosis)
• Insight and judgment

Physical Examination

• Neurological examination
• Sensory screening (hearing, vision)
• Signs of systemic disease

Investigations

• CBC, metabolic panel, LFTs, TFTs, RFTs
• Vitamin B12, folate, VDRL
• Urinalysis and urine drug screen
• EEG if seizures suspected
• Brain MRI: essential to rule out structural lesions, white matter changes, neurodegenerative markers
• Neuropsychological testing

10. Treatment

A. Non-Pharmacological Interventions (First-line for Dementia Psychosis)

• Environmental modifications: consistent routines, familiar environments, reduced stimulation
• Therapeutic activities and behavioral interventions
• Caregiver education and support
• Correction of sensory deficits (hearing aids, glasses)
• Social engagement and structured activities
• For LOS/VLOS: supportive psychotherapy, psychoeducation, family involvement

B. Pharmacotherapy

Key Principles in Geriatric Antipsychotic Use

• "Start low, go slow"
• Older adults are more sensitive to antipsychotic side effects
• Metabolic effects, extrapyramidal effects (EPS), orthostatic hypotension, sedation, cognitive worsening, falls are major concerns
• FDA Black Box Warning: Atypical antipsychotics are associated with increased mortality in elderly patients with dementia-related psychosis (mainly cardiovascular events and infections/pneumonia) - use with caution, informed consent required

Typical (First-Generation) Antipsychotics

• Higher risk of tardive dyskinesia (TD) - elderly are 5-6 times more vulnerable than young adults
• Higher EPS risk
• Haloperidol: Still used for acute agitation (IM formulation); low anticholinergic burden but high EPS
• Chlorpromazine, thioridazine: Avoid due to high anticholinergic and cardiovascular risk in elderly

Atypical (Second-Generation) Antipsychotics (Preferred)

Pimavanserin

• FDA-approved specifically for Parkinson disease psychosis
• 5-HT2A inverse agonist - does not block dopamine receptors
• Does not worsen motor symptoms of Parkinson disease
• Key advantage in geriatric population with Parkinson-related psychosis

Tardive Dyskinesia (TD) Management

• Older adults at 5-6x increased risk vs. young adults
• Valbenazine and deutetrabenazine (VMAT2 inhibitors) are FDA-approved for TD
• Clonazepam, vitamin E have limited evidence

Adjunctive Treatment

• Antidepressants for comorbid depression in schizophrenia (e.g., citalopram augmentation per RCT evidence)
• Mood stabilizers for aggressive/agitated behavior in dementia (valproate - evidence mixed; lithium for bipolar psychosis)
• Cholinesterase inhibitors (donepezil, rivastigmine) for Alzheimer/DLB psychosis - may reduce behavioral symptoms

11. Special Considerations

Psychosis in Lewy Body Dementia (DLB)

• Neuroleptic hypersensitivity - a potentially fatal reaction to typical antipsychotics and high-potency atypicals
• Quetiapine or clozapine preferred (low D2 blockade)
• Rivastigmine is the cholinesterase inhibitor of choice for DLB psychosis

Antipsychotic Withdrawal in Elderly

• Some stable older patients with chronic schizophrenia may benefit from dose reduction or withdrawal attempt
• Careful monitoring is required; relapse and exacerbation can occur
• Published cases describe successful withdrawal from antipsychotics in elderly inpatients with schizophrenia

Delusional Disorder Treatment

• Antipsychotic nonadherence is a common problem - patients do not believe they are ill
• Mild symptoms may be treated without medications
• Therapeutic alliance is critical; confronting the delusion directly is counterproductive
• Antipsychotics helpful for agitated patients whose delusions negatively impact social relationships or function

12. Summary Table: Key Distinguishing Points

Quick Navigation Guide

GERIATRIC DEPRESSION (20 Marks) covers:

1. Introduction & significance - WHO burden data, underdiagnosis
2. Epidemiology - prevalence figures (1-5% community; 40% chronic with partial remission)
3. Risk factors - biological and psychosocial
4. Clinical features - atypical presentation in elderly (somatic, anhedonia, cognitive), subtypes (psychotic, vascular, pseudodementia, minor)
5. Neurobiology - vascular hypothesis, inflammation hypothesis (IL-6, TNF, CRP), HPA axis, monoamines, dementia link
6. Comorbidities - cancer, dementia, Parkinson, cerebrovascular disease, suicide risk
7. Assessment - GDS, PHQ-9, Cornell Scale, full evaluation checklist
8. Treatment - pharmacotherapy (SSRIs, SNRIs, TCAs, newer agents with doses), ECT, psychotherapy (CBT, PST, IPT, Life Review), collaborative care model
9. Course & prognosis - relapse rates, chronicity predictors, dementia conversion

GERIATRIC PSYCHOSIS (20 Marks) covers:

1. Introduction & classification - EOS, LOS, VLOS, delusional disorder, dementia psychosis, psychotic depression, secondary causes
2. Epidemiology - prevalence rates, sex ratios
3. EOS vs LOS vs VLOS comparison table
4. Etiology & pathophysiology - estrogen hypothesis, neurodevelopmental vs. neurodegenerative, dopamine dysregulation
5. Clinical features - distinctive features of each type, partition delusions in VLOS
6. Differential diagnosis table
7. Role of sensory impairment - hearing loss, visual impairment as risk factors
8. Assessment - full workup including MRI, EEG
9. Treatment - non-pharmacological (first-line in dementia), antipsychotics (doses table: risperidone, quetiapine, olanzapine, aripiprazole, clozapine), pimavanserin, TD management, adjuncts
10. Special issues - DLB neuroleptic sensitivity, delusional disorder adherence, withdrawal in elderly
11. Summary comparison table