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Depression and Anxiety in Older Adults

Lee Solomon, MD

Assistant Clinical Professor, UT Family Medicine Chattanooga

Behavioral Health Associates, PC

Disclosures

• None

Objectives

• Review how depression presents differently in older adults

• Review how anxiety disorders present differently in older adults

• Review standard treatments for both and the adjustments that need to be considered in older adults

• Review new and novel treatments for both depression and anxiety

Adult Psychiatric Disorders

Continue into Old Age

Affective Disorders • Major Depression – becomes less common with

age • Dysthymic Disorder – (or atypical depression)

more common with age

• Seasonal Affective disorder • Bipolar disorder: incidence declines with age

• However, bipolar disorder remains a common diagnosis among aged psychiatric patients

• Type I and II

DSM-5 DIAGNOSTIC CRITERIA

FOR MAJOR DEPRESSION

• Gateway symptoms (must have 1)

• Depressed mood

• Loss of interest or pleasure (anhedonia)

• Other symptoms

• Appetite change or weight loss

• Insomnia or hypersomnia

• Psychomotor agitation or retardation

• Loss of energy

• Feelings of worthlessness or guilt

• Difficulty concentrating, making decisions

• Recurrent thoughts of suicide or death

Slide 5 Adult Psychiatric Disorders

Continue into Old Age

Anxiety Disorders

• Panic Disorder

• Social phobia

• Obsessive Compulsive Disorder

• Generalized Anxiety Disorder – becomes more common with age

• Posttraumatic Stress Disorder

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Symptoms of General Anxiety

Disorder

• GAD: chronic, difficult-to-control worry

• “I can’t turn my mind off”

• “I’m a worrier”

• Associated symptoms of GAD

• Sleep disturbance

• Fatigue

• Irritability

• Keyed up/on edge

• Muscle tension

• Difficulty concentrating (elderly may describe as memory)

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Aging and Depression • As many as 10% of older adults presenting to

primary care have clinically significant depression

• A recent meta-analysis revealed that primary care providers detected only 40-50% of depression among older adults and were less successful detecting depression among older adults than younger adults

• Up to 80% of elderly Americans with depression are treated by primary care

• Most older adults prefer to be treated by primary care because of comorbid medical conditions

• Depression in this population is often chronic or recurrent

Park & Unutzer. Psych Clin North Am. 2011, 34(2):1-19

Aging and Depression

• Loss of spouse/loved one or moving out of family home and other stressors may lead to the onset of a depressive episode

• 15-20% of older adults in the US experience depression

• Even mild depression may lower immunity and compromise patients’ ability to fight infections/cancers

Park & Unutzer. Psych Clin North Am. 2011, 34(2):1-19

Risk Factors for Depression in the Elderly

Cognitive

Impairment

Socioeconomic

Status

Unmarried Risk Factors

Caretaking

Responsibilities

Female

Social

Isolation

Chronic

Illness

Grief/Loss

Alcohol Abuse

Family History

of Depression

Protective Factors for Depression in the Elderly

Protective

Factors

Physical Activity

Strong Social Support

Religion Volunteering

Social Activities

Park & Unutzer. Psych Clin North Am. 2011; 34(2): 1-19

DIAGNOSTIC CHALLENGES IN

MEDICAL SETTINGS

• Symptoms of depressive and physical disorders often overlap, e.g.,

• Fatigue

• Disturbed sleep

• Diminished appetite

Depression can present atypically in the elderly

• Seriously ill or disabled persons may focus on thoughts of death or worthlessness, but not suicide

• Side effects of drugs for other illnesses may be confused with depressive symptoms

Slide 12

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DIAGNOSIS IN OLDER PATIENTS IS DIFFICULT

BECAUSE THEY . . .

• More often report somatic symptoms

• May be considered part of normal aging

• Cognitive impairment may interfere with diagnosis

• Practitioners may focus more on physical symptoms

• Less often report depressed mood, guilt

• May present with “masked” depression cloaked in preoccupation with physical concerns and complicated by overlap of physical and emotional symptoms

Slide 13 Warning Signs: Depression

• Physical • Aches, pains, or other physical complaints

• Marked changes in appetite

• Change in sleep patterns

• Fatigue

• Emotional • Pervasive sadness

• Apathy

• Decreased pleasure

• Crying for no apparent reason

• Indifference to others

Adapted from Schmall V, Lawson L, Stiehl R. Depression in Later Life: Recognition and Treatment. Pacific Northwest Extension publication. Corvallis, Ore, 1993

Warning Signs: Depression

• Changes in Thoughts and Feelings

• Feelings of hopelessness and helplessness

• Feelings of worthlessness

• Impaired concentration

• Problems with memory

• Indecisiveness

• Recurrent thoughts of death and suicide

Adapted from Schmall V, Lawson L, Stiehl R. Depression in Later Life: Recognition and Treatment. Pacific Northwest Extension publication. Corvallis, Ore, 1993

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Detecting anxiety in elderly persons

• Elders less up-front about anxiety Sx

• Asking about anxiety in several ways may help

(e.g., “anxious”, “worried”, “concerned”)

• “How do you feel in times of stress?”

• “What sorts of things do you worry about?”

• “How often do you feel that way?”

• “When you start worrying, what do you do to try to stop it?”

OLDER ADULTS AND SUICIDE

• Older age associated with increasing risk of suicide

• One fourth of all suicides occur in persons 65

• Risk factors: depression, physical illness, living

alone, male gender, alcoholism

• Violent suicides (e.g. firearms, hanging) are more

common than non-violent methods among older

adults, despite the potential for drug overdosing

Slide 17

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Suicide Rate is Higher in White Men

(rate per 100,000/age)

CDC. National Center for Health Statistics; 2000

Prevalence of anxiety disorders in

older adults

0%

2%

4%

6%

8%

10%

12%

Any anxiety d/o

Major depression

GAD

Phobia

Panic

OCD

Beekman et al., 1995, 1998

Early vs. late-onset GAD

0%

5%

10%

15%

20%

25%

30%

"All my

life"

Child Teens 20s 30s 40s 50s 60s 70s 80s

Le Roux, Gatz, & Wetherell, 2005

Comorbidity in late-life depression

and anxiety

Anxietyalone

w/comorbiddepression

Depression

alone

w/comorbid

anxiety

Beekman et al., 2000 (LASA)

Medications causing

symptoms of depression

• Anabolic steroids • Digitalis • Glucocorticoids

• H2 Blockers • Metoclopramide • Opioids • Some Beta-blockers

• Anti-arrythmics

• Anti-convulsants • Barbituates

• Benzodiazepenes • Carbidopa/Levodopa • Clonidine

Slide 23

Chronic Conditions impair health and functioning >65yo

• Degenerative Arthritis 50%

• Hypertension 40% • Hearing loss 30%

• Urinary incontinence 30% • Heart Disease 30% • Diabetes 15%

• Significant Hearing loss 15% • Significant vision loss 15%

• 14 to 37% medical outpatients, 40% inpatient

Slide 24

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Depression Guideline Panel. Depression in Primary Care: Vol 1. Detection and Diagnosis. Clinical Practice Guideline No. 5. Rockville, MD: US Dept of Health and Human Services. Public

Health Service, Agency for Health Care Policy and Research; no. 93-0550; 1993. Kessler RC et al. J Affect Disord. 1993;29:85-96. Kessler et al., JAMA 2003; Evans et al., J Clin Psych 1999; Astrom et al., Stroke, 1993; Tiller et al.,

Psychopharm 1992; Meaf et al., Neurology 1994; Cumming Am J Psych 1992.

• 16.2% of US population report at least one lifetime episode

• More than half of patients have first episode by age 40

• 25% of older cancer patients

• 25-50% of post-stroke patients

• 1/3 of Alzheimer’s patients

• 50% of Parkinson’s patients

• 30% of post-MI Patients

Epidemiology of Major Depression Pseudo-Dementia

• Type of depression that presents as dementia

• Symptoms of dementia resolve with depression treatment

• Usually of rapid onset

• Answers on mental status testing are inconsistent

• Complaints of memory problems are inconsistent with

functioning

• Other symptoms of depression are present

• Memory complaints may be the concentration symptoms of

depression

• High risk of developing dementia disorder in the future

• Patients with Major Depression also at higher risk of dementia

SSRI DOSING Drug Recommended Dose

(Younger Adults)

Citalopram

Escitalopram

20–40 mg/day

10–20 mg/day (QTc

prolonged)

Fluoxetine 20–40 mg/day (long T1/2,

2D6 blocker)

Paroxetine 20–50 mg/day (short T1/2,

ClCr<30 adj dose)

Sertraline 50–200 mg/day (mild 2D6)

Older adults – start with ½ dose and

increase to ½ maximum

Possible Risks of SSRIs in Elderly

• Suicide?

• FDA meta-analysis = protective in age >65

• Falls

• Association studies, some experimental

• Bleeding

• Particularly in “old-old”, h/o GI bleed

• Hyponatremia

• Tends to occur within 2 wk of initiation

• Risk factors: baseline low Na+, on diuretics

Suicidality and SSRIs: effects of age BUPROPION (SR or XL)

• Generally safe & well tolerated

• Ideal in Parkinson’s disease)

• activity of dopamine & norepinephrine

• Side effects:

• Insomnia, anxiety, tremor, myoclonus

• Associated with 0.4% risk of seizures

• Dose range: 200–450 mg/day (100-300 mg older adults)

Slide 30

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VENLAFAXINE ER

• Acts as SSRI at low doses; at higher doses SNRI (selective norepinephrine reuptake inhibitor)

• Effective for major depression & generalized anxiety

• Side effects:

• Nausea

• Hypertension

• Dose range: 75–225 mg per day ER version

• CrCl 10-70 25-50% decrease, CrCl 10 50% decrease

Slide 31 Desvenlafaxine

• Acts as SSRI at low doses; at higher doses SNRI (selective norepinephrine reuptake inhibitor)

• Effective for major depression & generalized anxiety

• Side effects:

• Nausea (less than venlafaxine)

• Hypertension

• Dose range: 50-100 mg per day

• CrCl 30-50 Max dose, CrCl <30 50% decrease

DULOXETINE

• Equally SRI and NRI (SNRI)

• Effective for major depression and Generalized anxiety,

FDA- approved for neuropathic pain

• Precautions: drug interactions (CYP450 1A2, 2D6 substrate), chronic liver disease, alcoholism, serum transaminase elevation

• Dose range: 20–120 mg per day

• (30 mg for 2 weeks, max 60 mg in older adult)

• CrCl <30 avoid use

Slide 33 MIRTAZAPINE

• Norepinephrine, 5-HT2 , and 5-HT3 antagonist

• Associated with weight gain, increased appetite

• May be used for nursing-home residents with depression & dementia, nighttime agitation, weight loss

• Dose range: 15-45 mg per day (7.5-30 mg older adults)

• May be given as single bedtime dose (sedative side effects); available in sublingual form

Slide 34

METHYLPHENIDATE

• No controlled data demonstrating efficacy for

depression

• Has been used for decades to treat major

depression

• May have role in reversing apathy, lack of

energy in patients with dementia or disabling

medical conditions

• Short term use, often as a bridge to other

treatment

• Can use with appropriate documentation

Slide 35 Slide 36

PHARMACOLOGIC ALGORITHM

Apathy, retardation

Insomnia, anxiety, anorexia

Pain Atypical, melancholic, anxious

bupropion mirtazapine duloxetine Venlafaxine, Desvenlafaxine

Initiate citalopram, escitalopram, or sertraline

If No response, switch to fluoxetine, OR switch

class based on symptom profile

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Duration of antidepressant treatment (days)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Monoamine levels

Depressive symptoms

Changes in neuroplasticity and

glutamatergic neurotransmission

Beyond Monoamines: The Neuroplasticity Hypothesis of Depression PHARMACOLOGIC ALGORITHM

• Partial Response – Augment

• Buspirone +/- melatonin

• Vitamin D

• Liothyronine

• Omega 3 fatty acids

• Light Therapy

• Exercise

Buspirone

• Good augmentation strategy for depression, stand

alone for anxiety

• Mechanism of action is 5HT1A agonist

• It works independent of endogenous release of serotonin.

• No sedation

• Takes around 2 weeks before patients notice results.

• Will not reduce anxiety in patients that are used to

taking BZDs because there is no sedation effect to “take

the edge off.

• Dose 10 to 30 mg BID

• Avoid in severe renal or hepatic impairment

Vitamin D and the Brain

• Influences brain development:

• cell growth, neuronal differentiation, axonal connectivity, neurotransmitter function, brain structure, learning, memory,

• Crucial role in neuroprotection, neurotransmission and neuroplasticity

• Regulates catecholamine levels

• Synthesizes acetylcholine, serotonin and dopamine

Role of Vitamin D in Brain Function

• Targets factors that lead to neurogeneration

• Anti-ischemic factors

• Good level promotes neurotrophic growth factors: NGNF, BDNF,GDNF

• Deficiency causes programmed death of the neurons (apoptosis)-proposed mechanism

DeLuca,G.C., Kimball,S.M., Kolasinski.J., Ramagopalan,S.V. & Eberes,G.C. (2013). Review: The role of vitamin D in nervous systems health and disease. Neuropathology and Applied Neurobiology, 39: 460.

At Risk for Vitamin D Deficiency

• Lower circulating Vitamin D

• Inadequate sun exposure in chronically ill, institutionalized or homebound

• poor dietary intake

• Aging (> 50 years)

• Obesity (body mass index > 30 kg/m2)-body

fat sequesters the vitamin

• Sun protective clothing/sunblock (SPF 30)

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From www.health.harvard.edu

The UV energy is insufficient for cutaneous Vitamin D synthesis from November through February

The UV energy is sufficient for cutaneous Vit D synthesis all year long

Vitamin D

• Deficiency <20 ng/mL

• Insufficiency 21-30 ng/mL

• Ideal in depression? 50ng/mL

• Best to monitor levels, in winter

• Dose Vitamin D3 (cholecalciferol)

• 1000-2000 IU (25-50mg) unknown level

• 3000-4000 IU (75-100mg) deficiency/insufficiency

Liothyronine • Increases:

• Thyrotropin releasing factor

• Corticotrophin releasing factor

• Brain Derived Neurotrophic factor

• Increases Serotonin receptors – increases serotonin in frontal lobes

• Use

• Check TSH,T3,T4 – investigate further if abnormal

• Avoid use with arrythmias and osteoporosis and warn of

potential risk

• Dose 25 mcg for at least a week then 50 mcg (12.5 in older

adults)

• Monitor at 3 months, every 6 months –TSH at or below lower limit

Innov Clin Neurosci 2017 Mar-Apr 14 (3-4) 24-29 PBRC 2005

Omega 3 fatty acids

Humans can synthesize other omega-3 fatty acids from Alpha-linolenic Acid (ALA):

Eicosapentaenoic acid (EPA): 20:5n-3

Docosahexaenoic acid (DHA): 22:6n-3

These two are usually referred to as marine-derived omega-3 fatty acids because they are abundant in certain species of fish

Whereas, ALA is considered a plant-derived omega-3 fatty acid

PBRC 2005

Omega 3 fatty acids • Omega-3 fatty acid levels to be lower in the plasma and

fat of individuals suffering from depression compared to controls

• Patients who took the EPA + DHA supplement also experienced less depression than those who took the placebo

• Dose:

• EPA 1000 – 2000 mg daily

• DHA <40% of EPA

• Generic Lovaza 2 -4 daily

• Take with meals, freeze

• Common SE – upset stomach, possible bleeding, diarrhea

Light Therapy

• Helpful for seasonal changes in mood

• Seasonal Affective Disorder (SAD)

• Bipolar Disorder with seasonal variation

• Atypical? Depression – hypersomnia, hyperphagia

• Suppresses Melatonin production

• Broad Spectrum light, 10,000 lux, UV filter

• Early morning better than midday or evening

• Start at first sign of seasonal change

• Trails should last at least 2 weeks

• 30 minutes at 14 inches – longer if further away

• Being inside without exposure to the sun can mimic seasonal

change

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Low Blue Light

• Residual symptoms of depression often hasten relapse

• Sleep is a frequent problem – especially initial insomnia

• Modern life with electric light sources inhibit the production of

melatonin preventing sleep onset

• Good sleep hygiene includes eliminating light

• Electronic pads often include color shift to orange option to aid

sleep

• Orange tinted glasses block blue/green light and promote sleep

• Wear for 1 to 3 hours before bed – remove after lights turned off

REASONS TO USE ECT

(Electroconvulsive Therapy)

• Effective for treatment of major depression

& mania; response rates exceed 70% in older adults

• First-line treatment for patients at serious risk

for suicide, life-threatening poor intake

• Standard for psychotic depression in older adults; response rates 80%

Slide 50

Ketamine

Ketamine (anesthetic)

Blocks NMDA receptors, evokes glutamate release

Induces schizophrenia-like symptoms in normal volunteers and exacerbates them in patients

Short-term, low-dose intravenous ketamine does not induce full range of psychotic symptoms in experimental setting

Transcranial Magnetic Stimulation (rTMS)

• Repeating stimulation of brain in areas associated

with depression using focused magnetic fields

• rTMS vs. ECT

• Studies generally favor ECT

• Older adults may need higher number of stimulations

• May be equal when psychotic patients not included

• More cognitive changes with ECT

• Level of brain atrophy correlated with response to rTMS

Medications efficacious for GAD

From clinical trials in young adults:

• FDA-approved: escitalopram, paroxetine, venlafaxine XR, duloxetine,

buspirone.

• Also efficacious: other SSRIs, benzodiazepines, pregabalin,

gabapentin, antihistamines

53 Problems With Benzodiazepines

Psychotropic

Odds

Ratio

of Fall

Benzodiazepine 1.4*

Antidepressant 0.9

Antipsychotic 1.5*

Sedative/hypnotic 1.1

• Benzodiazepines

efficacious BUT

• Already heavily

prescribed in elderly

• Associated with falls

• Associated with cognitive impairment

54

*P<.05.

Landi F, et al. J Gerontol A Biol Sci Med Sci. 2005;60:622-626.

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Citalopram in geriatric anxiety disorders

10

12

14

16

18

20

22

0 2 4 6 8

week of treatment

Ha

m-A

sc

ore

cit

pbo

Lenze et al, Am J Psychiatry, 2005

NAC

• N-acetyl Cysteine (NAC) • Glutamate modulator

• Glutamate Aids in NMDA transmission

• NMDA Transmitter blocked by memantine • NAC induces reuptake of glutamate by glia cells

thus decreasing NMDA transmission • Studied with some success in OCD, Skin picking and

hair pulling

• May aid to lower worry • Dose: 600 mg to 3000 mg

• Generally start with 600 mg then increase in one to two weeks to 1200 mg

Cannabidiol (CBD)

• Cannabidiol (CBD) helps to balance the neurotoxic effects of Tetrahydrocannabidiol (THC) in marijuana

• CBD being extracted from hemp

• Growing hemp nationwide has recently been legalized

• Studies in anxiety disorders show benefit in GAD,

Panic disorder, Social Anxiety disorder and OCD • Possible benefit in PTSD when used acutely

• Few studies on dosing • Most studies done with acute dosing only • Study dosing ranges widely 50 to 500 mg

• Patients doing naturalistic study • 20 to 40 mg up to TID seems most effective

• Also may be helpful for sleep and pain

• Many elderly persons will prefer

psychotherapy to medication

• CBT most efficacious in those who can

be adherent to homework

• Cognitive impairment can interfere

Psychotherapy in late-life GAD

Wetherell, Hopko et al., 2005; Mohlman & Gorman, 2005

59

When to choose psychotherapy

• Motivated, cognitively intact patient

• Phobias

• Consider delaying medication until after Tx

• Will not accept medication

• Partial response to medication

• Availability of high-quality psychotherapy

SUMMARY

• In older adults, depression is

• Common (especially “minor” depression)

• Associated with morbidity – especially

suicide

• Difficult to diagnose because of atypical presentation, more somatic concerns,

overlap with symptoms of other illnesses

• Just as treatable as in younger patients

when adjustments for age considered

Slide 60

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Summary

• In older adults, anxiety is:

• More commonly Generalized Anxiety Disorder which increases with age

• Just as treatable as younger patients

• For both depression and anxiety:

• Neuro-regenerative approaches can aid as adjunctive treatment

• Novel new treatments may hold additional benefit