A L A N A I G L E W I C Z , M D

A I G L E W I C Z @ U C S D . E D U

A S S I S T A N T C L I N I C A L P R O F E S S O R

U N I V E R S I T Y C A L I F O R N I A , S A N D I E G O

&

V A S A N D I E G O H E A L T H C A R E S Y S T E M

WHAT EVERY CLINICIAN NEEDS TO KNOW ABOUT GRIEF,

BEREAVEMENT AND DEPRESSION

Ms. B

Ms. B, a 75 year old woman who comes for an evaluation because she is not getting past her intense grief over her deceased husband who died suddenly following a myocardial infarction 4 years ago. Although she thinks about her husband daily, she avoids looking at pictures, visiting the grave-site or even going to places they used to enjoy together to try to ward off the intense bouts of misery these reminders provoke. Ms. B is tearful, recalling how wonderful her husband was, that he was her soul-mate, and he loved her in a way no one else ever did.

Ms. B (2)

Ms. B has been ruminating over thoughts about how and why her husband did not really need to die. Her husband had seen his doctor a week before he died and she is plagued by angry thoughts about the doctors who did not diagnose the impending heart attack. She cannot get the idea out of her mind that his doctor could have suspected that her husband had blocked arteries and done something to save him.

She often neglects to take her hypertension medication knowing this could be dangerous and endorses that she wishes to leave death to chance. She has come close to taking an overdose of her hypertension medication but it is against her religion to take one’s own life. Religion used to be source of comfort, but she no longer attends church regularly or finds companionship or support from the church community. Ms. B maintains that no one can help her because no one can bring her husband back.

Ms B’s physician is puzzled. Ms B is tearful and sad, but does not meet criteria for MDD. The physician wonders if this could be normal grief . It has been a long time since Jim died, but knows that everyone grieves in their own way.

Ms B (3)

What is the nature of grief? When does it end? Should grief be treated? When?

What is complicated grief? Should it be treated? Can it be treated? How?

When and how should “depressed” bereaved people

be treated?

Questions to Ponder

Outline

Terminology Grief and Bereavement Acute Integrated

Complicated Grief Suicide Bereavement Distinguishing Grief from Depression Bereavement Related Depression

Loss and Grief

Loss is universal and often the most painful of human experiences

In both our personal and professional lives, we will face meaningful losses regularly

For every person who dies, an average of five - six loved ones are left behind

Grief is the response to loss

Terminology

Grief: constellation of feelings, behaviors, cognitions, and changes in function associated with loss of any kind

Bereavement: Grief specifically tied to the death of a “meaningful” other DSM-III,IV – depressive syndrome within 2 months of death

Mourning: Behavioral , social and cultural rituals of grief

Complicated Grief (aka, prolonged acute, unresolved, traumatic grief): Prolonged, intense grief requiring intervention Persistent difficulty accepting the death; recurrent pangs of intense grief;

preoccupation with thoughts and images of the deceased; avoidance of reminders of the loss; and difficulty adjusting to life without the deceased

WHAT IS THE NATURE OF GRIEF?

Erich Fromm

A Universal Reaction

To spare oneself from grief at all costs can be achieved only at the price of total detachment, which excludes the ability to experience happiness

Grief is Painful

“The loss of a loved person is one of the most intensely painful experiences any human being can suffer. Nothing but the return of the lost person can bring true comfort; should what we provide fall short of that it is felt almost as an insult.”

John Bowlby Loss pp 7-8

1980

Grief: 2 Forms

Acute Integrated

1. The transition is instinctive 2. It usually begins within months 3. Integrated grief is life long

ACUTE GRIEF

Acute Grief Contains a Mix of Emotions

Unpleasant emotions Sadness Anxiety (e.g., about how the

person will manage) Guilt (e.g., about not doing

enough and about surviving) Anger (e.g., about others not

doing or caring enough) Shame (e.g., about sense

of vulnerability and uncontrollable emotionality)

Pleasant emotions Enjoyment in recalling happy

times Amusing anecdotes Pride in honoring the

deceased Warmth in recollecting

closeness Relief from burden Pleasure and joy in being alive

16

Healing after Grief: From Acute to Integrated Grief

Acute grief may last most of the day, most days for up to 6 months, and then recurs transiently

Grief does not fully remit and can periodically surge, as in “difficult times” of the year (holidays, anniversaries, stress, other losses)

Grief usually moves from a place where it dominates a person’s mind to reside more comfortably in the person’s heart.

INTEGRATED GRIEF

Integrated Grief

Enduring sorrow and longing, along with memories of the deceased become assimilated into the life and mind of a bereaved person Usually present by about 6 months after a death Evolves over time

Characteristic features Acceptance of the death Interest and engagement in ongoing life A mix of emotions related to the deceased with positive

emotions usually dominant Thoughts and memories of the deceased accessible but not

preoccupying

19

George And Gracie

“I visit my dear Gracie weekly. I leave fresh flowers and tell her about my week. I tell her about the kids; I tell her what I’m doing. And you know what? Not once has she answered back. I know she’s listening and that’s very reassuring.”

Helping Bereaved

Dos Direct expression of sympathy Acknowledgement that the

clinician does not know exactly what the bereaved person is going through

Talking about the deceased, saying his/her name

Inquiring about the circumstances of the death

Encourage expression of feelings

3 “Hs”: hush, hug and hang out

Don’ts Be casual or passive (“call me

when you want to talk” or “let me know what I can do”)

Imply death for the best or acceptable

Convey the bereaved person is strong and will/should get over it

Avoid discussion of the death or the person who died

Prigerson and Jacobs,2001; Rene Tietsworth, 11/05/04

“A trouble shared is a trouble halved”

Considerations for Clinicians

Crying

Condolence cards

Funeral/memorial attendance

Complicated Grief

Characteristics Consequences Continued difficulty

accepting the death beyond 6 months

Persistent strong yearning Anger and bitterness Preoccupation and/or Excessive avoidance Futility about the value of

ongoing life and relationships

Ongoing pain and suffering Impaired functioning and

disability Increased risk for cancer,

cardiac disease, hypertension, substance abuse

Co-morbid depression Elevated rate of suicidal

ideation and attempts

Failure to Progress from Acute to Integrated Grief

Tends to persist endlessly without treatment

BA SED ON A SIM PLE PRINCIPLE:

A CUTE GRIEF WILL PROG RESS INSTINCTIVELY TO INTEG RA TION IF

COMPLICA TIONS A RE A DDRESSED A ND THE NA TURAL MOURNING

PROCESS IS SUPPORTED

Complicated Grief Treatment

CGT: A Targeted Treatment

Integrates interpersonal psychotherapy, prolonged

exposure, motivational and cognitive behavioral treatment

strategies

Based on a model of coping with grief that posits

contemporaneous oscillating attention to loss-focused work

and life-focused work

Loss

Life

CGT

IPT

PE

MI

CBT

Strategies Procedures

Address complicating thoughts, feelings and behaviors

Establish a rhythm of oscillation between confrontation and comfort

Attend to dual processes of reflection upon the death (loss-focus) and re-envisioning the future (restoration-focus)

Grief monitoring Psychoeducation Imaginal and situational

revisiting exercises Memories and pictures Imaginal conversation with

the person who died Involving significant other Attention to self care, core

values and meaningful future plans

Complicated Grief Treatment (Cont.)

CGT Produced Better Results Than Standard IPT

0%

10%

20%

30%

40%

50%

60%

70%

INTENT-TO TREAT COMPLETERS

51%

66%

28% 32%

CGT IPT

chi-square=7.56, df=1, p =0.006 chi-square=5.07, df=1, p <0.024

NNT: Completers: 3 ITT: 4

Shear et al JAMA 293:2601 2005

% B

ette

r or

ver

y m

uch

bett

er

Do Medications Play a Role?

59.00%

42.00% 40.00%

19.00%

38%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

CGT IPT Escitalopram

With antidepressant Without antidepressant

Simon et al, 2009

Outcome With And Without Antidepressant Medication

HEALING EMOTIONS AFTER LOSS (HEAL) 4 Sites:Columbia (Shear), MGH (Simon), Pittsburgh (Reynolds) , San Diego (Zisook)

Baseline Assessment

CIT/CM N=125

PBO/CM

N=125

CIT + CGT

N=125

PBO+ CGT

N=125

Post-Treatment

Assessment

16 weeks

Referrals: Ilanit T. Young (858) 552-7598 ityoung@vapop.ucsd.edu

6 months

Back to Ms. B: Should She Be Offered Treatment For Her Grief?

She does not meet criteria for major depression She has not accepted her husband’s death She continues to yearn and long for him and remains

preoccupied with thoughts and memories of Jim She has little evidence of interest in ongoing life or other

people Anger, bitterness and guilt guide most of her thoughts There is no evidence of healing or of integrated grief; rather

it is as though Jim died very recently Ms B meets criteria for complicated grief She SHOULD be treated.

SUICIDE BEREAVEMENT

“WHEN A PATIENT SUICIDES, THE PROBLEM CAN NO LONGER BE SEEN

ONLY AS AN INDIVIDUAL AND FAMILY TRAGEDY, TO BE BORNE IN SECRECY

AND STIGMA. SUICIDE IS EVERYBODY’S BUSINESS.”

- - T H E P S Y C H O L O G I C A L S O C I E T Y O F L O N D O N , P O L I C Y D O C U M E N T O N S U I C I D E , S E C T . 9 . 2 .

Gaffney et al, Death Studies, 2009

When a Patient Suicides

An occupational risk “There are 2 kinds of psychiatrists: those who have lost a

patient to suicide and those who will.”

>50% of psychiatrists have lost at least one patient to suicide Many more than once

Our responses are human responses

Impact of Patient Suicide on Residents/Physicians

• Shame – “I am stupid or lazy” • Doubt – “I am in the wrong career” • Guilt – “Shoulda, woulda, coulda, if” • Rejection, abandonment, anger, relief • Other stress, trauma and loss symptoms

Common reactions

• Depression • ASD and/or PTSD • Complicated Grief

Less common reactions

Important Issues

Death happens – MDD can be a fatal disease Notifying risk management, service chiefs, training directors Notifying and talking to family Funerals Condolence cards Permission to grieve Self care Support from program/colleagues Debriefing M&Ms

Professional help

DISTINGUISHING GRIEF FROM DEPRESSION

Distinguishing Grief from Depression

Quantitatively similar Sadness Anhedonia Guilt Suicidality

Qualitatively different Both can be intensely painful Yet, fundamentally different constructs

Grief Major Depressive Episode

Positive emotions intermixed with sadness

Loss of pleasure related to longing for the deceased loved one

Guilt or remorse is focused on letting the person down

Wish to die is related to longing for reunion

Sad mood is pervasive Loss of interest and

pleasure is pervasive Guilt is related to feeling

worthless or like a bad person

Suicidal thinking is related to a feeling of not deserving to live

Distinguishing Grief from Depression

Distinguishing Grief from Depression

When in doubt consider Time Severity Past and family history

Time since death is not the distinguishing

characteristic

Not either/or, but potentially both

Is Depression Occurring After the Death of a Loved-One Depression?

WHEN IS DEPRESSION NOT DEPRESSION?

Consider the case of Mr. A

Mr. A is 73-year-old male whose wife of 50 years died 5 weeks previously. He has no appetite, has lost 8 lbs in the past month, consistently awakens at 4 a.m, “can’t think straight,” and no longer takes any takes pleasure in customary activities. He denies feelings of guilt or worthlessness. Although he denies suicide intent, he confides that he wishes to join his dearly departed wife. When discussing his wife, he shows moderate psychomotor agitation and spends most days mindlessly sitting in front of his television.

Questions Arising From Mr. A

If Mr. A. meets all symptom and duration criteria for MDD, but falls within “2 month” period of DSM-IV bereavement exclusion, what should you diagnose? Do you try to “normalize” the experience for Mr. A. (“Anybody in

your position would feel as you do”) & advise against medical treatment?

Or

Do you formulate this as “clinical depression” and recommend psychotherapy and/or an antidepressant?

The Relationship Between Bereavement and Depression Remains Controversial

Many believe that “depression” is a normal consequence of bereavement MDD shouldn’t be diagnosed MDD shouldn't be treated

May interfere with grief DSM vs. ICD

Does the data support this belief? No: depression following bereavement is: Common Persistent Poor outcome Responds to treatment

The “Fallacy of Misplaced Empathy” (Ronald Pies, MD)

MDD Following Bereavement Is Common: Overall Rates MDE Following Bereavement Higher Than

Expected For At Least 2 Years

0

5

10

15

20

25

2 months 13 months 25 months

Percentage with MDD Risk factors Past and family MDD Death by suicide Lack of treatment

Greatest risk for MDE 13 months is MDE 2 months

Married Controls (4% MDD)

aZisook and Shuchter, 1993 bZisook et al, 1997

Summary of 24 Longitudinal Studies

Bereavement related MDD is about equally prevalent in children, adults and older adults

In controlled studies, rates of MDD consistently greater in recently bereaved than non-bereaved controls

Bereavement-related MDD is persistent over time

• In panel studies beginning pre-bereavement, rates of MDE and dysphoria already higher in soon to be widowed than those who will remain married

• Pre-bereavement MDE and dysphoria predict post-bereavement BRD • Dysphoria and MDE are highest in months after death, decrease over time, but remain

elevated, compared to non-bereaved, for 1-3 years

Consequences, including dysfunction, disability, changes in sleep architecture, immune impairment and suicidal ideation, are similar to MDD

Bereavement-related MDD responds to antidepressant treatment

Zisook and Kendler, 2007; Zisook et al, 2008

Does Bereavement-Related Major Depression Differ from Major Depression Associated with Other Forms of Stressful

Events? BRD (N=82) SLERD (N=224) Significance

Demographics

Age at index episode 35.1 ± 7.4 33.0 ± 8.2 0.04

Gender (% female) 72.0 56.3 0.01

DSM-IV Exclusion Criteria (%)

Duration > 2 months 32.9 43.3 0.12

Psychomotor retardation 39.0 41.1 0.64

Suicidal ideation 14.6 22.8 0.21

Severe work impairment 17.1 14.9 0.77

Meets Criteria for “Uncomplicated Loss” 28.1 24.6 0.53

Treatment Seeking For Index Episode (%) 26.8 36.2 0.05

Kendler, Myers and Zisook, AJP, 2009

No difference in duration of episodes, age at first episode, number of previous episodes, likelihood of subsequent episodes, co-morbid anxiety or substance-use disorders or risk of lifetime MDD in co-twin

What are the Implications for DSM-V?

Findings - BRD is: similar to other types of MDD often associated with pain and considerable suffering as often associated with those features of MDD the DSM says are more

characteristic of MDD than of “normal” grief as other, non-bereavement related depression

highly comorbid with a number of Axis I conditions known to be associated with MD

genetically influenced tends to be chronic and recurrent and responds to antidepressant treatment

Conclusion: “To continue the bereavement exclusion in DSM-V would be to provide license to bereaved individuals, their families and health care providers to continue ignoring signs and symptoms of a potentially debilitating, life-threatening, yet treatable disorder”.

Kendler, Myers and Zisook et al, 2009

Treatment of Bereavement-Related MDD

“Give sorrow words: the grief that does not speak whispers the o’er-fraught heart, and bids it break”.

Shakespeare, Macbeth

“Your tale is very sad, Ben. I’m almost sorry I took an anti-depressant.”

Treatment of Bereavement Related MDE

No RTCs of Psychotherapy 5 open studies antidepressant medication Jacobs et al, 1987 Pasternak et al, 1991 Zisook et al, 2001 Oakley et al, 2002 Hensley et al, 2006

1 Placebo controlled study – Reynolds et al, 1999

Bereavement Related MDE Medication Study Conclusions

• depression does • depression responds to standard treatment • grief responds in kind

Treating depression does not interfere with

grief

MDE associated with bereavement responds to treatment like other,

nonbereavement-related MDE

Role of psychotherapy not yet clear

Summary Acute grief is painful and disruptive – but usually evolves into less painful “integrated” grief • Grief is not a medical condition • Acute and integrated grief do not require professional treatment

Acute grief can become “prolonged” (i.e., “complicated grief”)and/or be accompanied by MDD

• Complicated grief and bereavement related major depression can be identified and should be treated

“In the depth of winter, I finally learned that within me there lay an invincible summer”.

Albert Camus

Cognitive Behavioral Therapy with Older Adults Steven R. Thorp, Ph.D.

VA San Diego Healthcare System Center of Excellence for Stress and Mental Health

University of California, San Diego

Outline

Older Adulthood and Mental Health

Cognitive-Behavioral Therapy Mood Disorders in Older Adults

Anxiety Disorders in Older Adults

Assessment Guidelines

Treatment Guidelines

Barriers to Mental Health Services for Older Adults

Older patients’ reluctance to seek psychiatric treatment; medication noncompliance1 Under-treatment by primary care physicians; General medicine physicians provide up to half of all outpatient mental health care2, but they often fail to prescribe adequate pharmacotherapy or refer for mental health specialty care3 Ageism in assessment (especially neglecting to ask questions about psychological problems, especially childhood problems and early traumatic events) and treatment (Freud called adults over 50 “ineducable”)4

1Bortz & O’Brien, 1997; 2Regier et al., 1993; 3Rogers et al., 1993; 4Freud, 1905

Treatment Preferences

Among older medical patients, 79% said they would use any psychological services However, 72% preferred to talk with their primary care provider, while 46% said they would speak to a mental health worker or nurse about their problems Only 34% said they would attend “group therapy,” but 68% said they would attend “psychoeducational classes”

Areán et al., 2002

CBT

Cognitive-Behavioral Therapy (CBT) is the most studied (and often shown to be the most successful) psychotherapy in a variety of populations1

CBT is a very general term (psychotherapies that address “thoughts” and “behaviors”), but it requires certain elements

1Barlow (2001)

Characteristics of CBT

Brief & time-limited Involves client-therapist collaboration Structured, with active and directive therapist Views thoughts as hypotheses to be questioned and tested Present focused and problem focused Involves homework Can be done in individual, group, couples, or family formats Adapted from National Association of Cognitive-Behavior Therapists (2003)

Hallmarks of CBT Sessions

Choosing specific goals to target within a specific number of sessions (often 12-20, 50-90 minutes) Setting an agenda for each session Addressing problematic thoughts and behaviors, and noting how they influence mood and progress toward goals Review of session Assigning homework to be done between sessions

The Basic Theory Underlying CBT

Feelings

Behaviors Thoughts

Common CBT Techniques

Behavioral activation and scheduling activities Cognitive restructuring Cognitive rehearsal Exposure Role playing

CBT and Pharmacotherapy

Medications for older adults sometimes work well, but complications include:

sensitivity to side effects

dosing “window” issues

potential for harmful interactions with other medications

potential for addiction and falls

comorbid medical and neurological disorders

costs of lifetime use

CBT and Pharmacotherapy

CBT has yielded effects sizes as large or larger than pharmacotherapy or other forms of psychotherapy1, and patients are less likely to relapse (vs. medications)2

CBT + medications generally superior to medications alone for older adults3

1APA, 2000; 2Hollon et al., 2002; 3Areán & Cook, 2002

Mood Disorders

In Older Adults Depression

Depression and Axis II

Bipolar Disorder

Depression in Older Adults

Depression is the most common emotional disorder in older adults (15% in community, higher in ill populations)1,2 and there is a poor prognosis for untreated depression in the elderly3

It is important for primary care physicians to detect psychiatric issues and address them (by treatment or referral)

1Bortz & O’Brien, 1997; 2Reynolds & Kupfer, 1999; 3Burvill et al., 1986

CBT for Depression

CBT for geriatric depression has been studied by different investigators, using diagnostic interviews, treatment manuals, supervision of therapists, and control conditions1

Among older patients studied over a 10-year period, 75% showed clear improvement or full remission after 15-20 outpatient sessions of CBT, though 30-40 sessions worked best for those with more chronic or complex problems2

1Areán & Cook, 2002; 2 Gallagher et al.; 1987

Efficacy of CBT and Depression

Social Problem Solving Therapy (a type of CBT) works well for treating depression in older adults1

From RCTs of older adults, CBT appears to be superior to usual care and no treatment for MDD and depressive symptoms, with maintenance of gains for up to 3 years2

CBT in group format also works well for older adults with depression3

1Areán et al., 1993; 2Areán & Cook, 2002; 3Gallagher-Thompson et al., 1990

Depression and Axis II

Although clinical lore suggests that Axis II disorders “burn out” in late life, 13% of community-dwelling older adults have personality disorders (PDs)1 and PDs often occur with geriatric depression2

Older patients with MDD have higher rates of PDs than those with other Axis I (or no Axis I) disorders3

Among older adults with depression, one-third had a PD, and those with PD were less likely to benefit from short-term psychotherapy4

1Sidelitz, 2001; 2Thorp & Lynch, 2005; 3 Bizzini, 1998; 4Thompson, Gallagher, & Czirr, 1988

Dialectical Behavior Therapy

Dialectical Behavior Therapy (DBT) is a CBT that integrates mindfulness skills; designed to treat borderline personality disorder1

Study 1 (34 depressed older adults): 47% in medication only group had depression in remission at posttreatment; 71% of those in medication plus DBT skills groups were in remission at posttreatment2

Study 2 (35 medication resistant, depressed plus PD patients): After treatment, 50% in med group were in remission for depression and 71% of the DBT plus med group were in remission; the latter group had lower interpersonal sensitivity and aggression scores2

1Linehan, 1993; 2Lynch et al., 2007

Bipolar Disorder

Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

Participants with Bipolar I or II disorder and depression randomized to one of 4 arms:

Collaborative care: n=130 or

Three types of intensive psychotherapy (n=163): CBT

Family-Focused Therapy

Interpersonal and Social Rhythm Therapy

Miklowitz, 2007

STEP-BD Study Results

No differences among the 3 intensive psychotherapies

Intensive psychotherapies yielded significantly higher year-end recovery rates and shorter times to recovery than patients in collaborative care

Miklowitz, 2007

Anxiety Disorders

In Older Adults

CBT does not appear to reduce anxiety for older adults as well as it does for younger adults1

Acceptance and Commitment Therapy (ACT) integrates mindfulness as well as traditional CBT methods. We found no dropouts from ACT in a preliminary trial and it reduces anxiety, but it did not work as well as in younger adults2

1Wolitzky-Taylor et al. (2010); 2 Wetherell et al. (2010)

Meta-Analysis of Behavioral Treatments

We1 screened 300 studies and compared effect sizes from 19 clinical trials (with sample size of at least 5) of behavioral treatments for geriatric anxiety (CBT alone, CBT with Relaxation Training, or RT alone)

Mostly Generalized Anxiety Disorder and Panic Disorder, with some Social Anxiety, Simple Phobias, and unspecified anxiety symptoms

No studies of Obsessive-Compulsive Disorder or Posttraumatic Stress Disorder (PTSD)

Treatments were more effective than wait lists or active controls; comparable to effects in the general population

1Thorp et al, 2009

Meta-Analysis of Behavioral Treatments, cont.

Surprise finding: CBT did not appear to add anything beyond RT alone, and one could argue that RT is easier to teach and administer Interpret with caution, given different sample characteristics and control conditions

1Thorp et al, 2009

Psychotherapy with Older Adults with PTSD

No controlled trials of psychotherapy for PTSD in older adults1 Only 7 peer-reviewed empirical studies of older adults with PTSD, and the modal (most common) sample size is 1 Exposure therapies are most studied in general population, but concerns about older adults being too frail or not being able to “handle” exposure therapies2

1Thorp et al, 2009; 2Hyer & Woods, 1998

Exposure Therapy for Older Veterans with PTSD

Thorp, S. R., Stein, M. B., Jeste, D. V., Patterson, T. L., & Wetherell, J. L. (2012). Prolonged exposure therapy for older veterans with posttraumatic stress disorder: Pilot study. American Journal of Geriatric Psychiatry, 20, 276-280.

Pilot Study

Pilot study of older male veterans with PTSD from military traumas

Objectives: Determine feasibility of recruitment, assessment, and the treatment protocol

Design: Pre/post (“open label”) trial of Prolonged Exposure (PE) therapy (n = 11), with a comparison to a separate Treatment as Usual (TAU) sample from the same clinic (n = 53)

Subjects

Comparison of Groups

PE TAU

Variable % Mean

(SD)

% Mean

(SD) Age 63.1 (7.1) 61.9 (5.3)

Education (years) 14.0 (1.6) 14.1 (1.9)

Married 50 51

Caucasian 88 60

Time Since Trauma 39 years 40 years

Prolonged Exposure Therapy (PE)

PE is a manualized treatment for PTSD1, and it is the most well validated type of psychotherapy for PTSD2 Protocol: Six weeks of 90-minute individual sessions for imaginal exposure (talking aloud, in detail, about worst traumatic event) plus weekly homework (in vivo exposure; engaging in feared but safe activities)

1Foa, Hembree, & Rothbaum, 2008; 2Bradley et al., 2005

PE Theory

PTSD symptoms remit by 3-4 months after traumatic events for most individuals Individuals who develop chronic PTSD tend to avoid people, places, and things (e.g., objects, sounds, thoughts, feelings) linked to the trauma and have unhelpful thoughts Treatment: Planned, extended contact with feared memories and situations will decrease the physiological response over time, making PTSD symptoms less intense

1Foa, Hembree, & Rothbaum, 2007

Results

Clinician-Rated PTSD (CAPS)

0

10

20

30

40

50

60

70

80

90

100

PE TAU

PrePost

*p<.05, Wilcoxon Matched Pairs Signed Ranks Test

CAPS ≥ 60 indicates clinically

significant PTSD

* *

Cohen’s d = 1.7 Cohen’s d = 0.5

Thorp et al., 2012, AJGP

Conclusions from Pilot

Early indications that older veterans can be recruited, that exposure therapy is well tolerated, and that exposure can reduce PTSD symptoms

Results should be interpreted with caution, given the small sample size, but the data suggest that exposure therapy may be promising for older male veterans with PTSD

PE vs. Relaxation in Older Veterans

VA Career Development Award (Thorp, PI): Five-year randomized clinical trial: PE vs. Relaxation Training for Older Adults (age 60 and older) with PTSD Independent clinical assessments with follow-up assessments every 6 months during study Testing to examine cognitive functioning as a potential predictor of treatment outcome Final data from 87 veterans will be collected this year

Risk of Dementia Among Veterans

There is a link between PTSD and dementia1

Researchers followed 181,000 veterans over six years, including more than 53,000 with PTSD

Those with PTSD were more than twice as likely to develop dementia

1Yaffe et al., 2010

Risk of Dementia Among Veterans

A meta-analysis of cognitive functioning in older adults with PTSD found that trauma exposure is linked to worse performance on learning tasks and PTSD is linked to poorer memory1

1Schuitevoerder et al., in press, Journal of Anxiety Disorders

Cognitive Impairment and Psychotherapy

Depression

For older adults with depression, cognitive strategies worked well for mild dementia, behavioral strategies worked best for more advanced cognitive impairment1

1Teri & Gallagher-Thompson (1991)

PTSD

In study of 145 sexual assault survivors with PTSD, older women in exposure therapy and younger women in cognitive therapy had best outcomes (authors posit this is due to “long standing cognitions” in older group)1

Among veterans with PTSD, those with poor verbal memory and narrative encoding deficits were less likely to be responsive to CBT (differences not due to IQ, attention, PTSD severity, depression, time since trauma, or substance misuse)2

1Rizvi, Vogt, & Resick, 2009; 2Wild & Gur, 2008

Residential Treatment (CPT) of PTSD in Veterans with

Comorbid TBI

Chard et al. (2010)

PTSD

Sev

erity

(CA

PS)

Residential Treatment (CPT) of PTSD in Veterans with

Comorbid TBI

0

10

20

30

40

50

60

70

80

90

100

Mild TBI (n = 28) Moderate-Severe TBI (n = 14)

Baseline Post-Treatment

Chard et al. (2011)

PTSD

Sev

erity

(CA

PS)

Treatment Response by Age

We examined data from a recent psychotherapy trial to see if there were differences in PTSD pre- and post-treatment between veterans aged 60 and older (n = 60) and younger (n =139) veterans

PTSD Severity C

APS

Each *p<.05

Assessment Guidelines

Assessment

Assess: Physical exam

History of work, relationships, disorders

Traumatic event, if applicable

Social support

Cognitive status

ADLs (e.g., grooming, shopping, cooking, med management)

Thorp & Lynch, 2005; Weintraub & Ruskin, 1999

Assessment, cont.

Older adults may report problems with appetite, sleep, or cognitive problems rather than mood problems1,2; they may resist “airing dirty laundry”

It is often helpful to begin assessments by inquiring about more somatic issues and then inquire about anything that may be causing them stress

1APA, 2000; 2Reynolds & Kupfer, 1999

Assessment, cont.

Vision problems are more common in older adults – these problems can lower cognitive testing scores1 and macular degeneration can mimic visual hallucinations)2

Try to print in larger, high contrast font (e.g., 16 point bold) More than half of adults aged 70 or older have hearing problems, so may need to speak louder than normal; assess history of hearing treatments, and consider hearing problems in group therapy setting

1Lezak, 1995; 2Holroyd et al., 1992

Assessment, cont.

Consider stigma: “How much do you do X behavior (or feel X feeling)” vs. “Do you ever do (or feel) X?” (especially about violent, sexual, or illegal activities)

Recommend the use of several measures and lower cutoffs

Use observation and collateral reports (family, friends, caregivers) in addition to self-report

Thorp & Lynch, 2005; Weintraub & Ruskin, 1999

Treatment Guidelines

Language Guidelines

Avoid slang and jargon in speech with older adults (unless they use it)

Avoid terms overly linked to “mental problems” (e.g., feeling “down” vs. “depressed”) or sound like psychobabble or “new age” treatments (“working with your inner child”)

“Classes” vs. “Group Therapy”

Instead of, “Would you like help with your mental problem?” Or “Will you go to a psychotherapist or psychoanalyst?” , try “How would you feel about talking to someone about this common problem?”

Thorp & Lynch, 2005; Weintraub & Ruskin, 1999

Treatment Guidelines

Professional, more conservative dress

Use proper name and title (both ways)

More time for presentation and review

Repeat often and give written instructions, calendars, or other visual aids

Record sessions for clients to review

Areán, 2003; Massey, 1997; Thompson, 1996; Thorp & Lynch, 2005

Treatment Guidelines, cont.

Couples and family interventions/support

Visual and other modes of learning

Metaphors for psychotherapy, such as “exercising”, “tracking blood sugar”, or “getting shots”)

Provide more practical assistance and concrete recommendations

Take breaks as needed; perhaps extend length of sessions or duration of treatment

Natural Advantages of CBT for Older Adults

Includes psychoeducation about disorders and treatment (to reduce stigma and normalize problems)

Strong relationship between therapist and client and collaborative agenda

Measureable goals

Continual reviews of new information and practice in and out of session

Areán, 2003; Massey, 1997; Thorp & Lynch, 2005

Summary and Future Directions

There is a growing need for mental health treatment for older adults Older patients are often willing to utilize CBT and may benefit from CBT alone or in conjunction with pharmacotherapy Presentation and language can encourage older adults to initiate and maintain CBT Assessment and treatment should be multi-modal and multi-faceted

Summary and Future Directions

CBT is effective in improving symptoms and psychosocial outcomes in depression, with less evidence for bipolar disorder and anxiety disorders

Newer CBT interventions include mindfulness and acceptance strategies in addition to more traditional CBT strategies that target changes in thoughts and behaviors

Summary and Future Directions

Cognitive remediation or training may be an appropriate intervention for older adults with PTSD and cognitive deficits

Compensatory cognitive training has shown positive effects on cognition and functional capacity in severe mental illness, even among older clients1,2

1Twamley et al., 2011; 2Twamley et al., in press

Thank You!

From Symptoms to Circuits in From Symptoms to Circuits in y py pPsychopharmacology: Imaging Psychopharmacology: Imaging

Brain Circuits and Applying Brain Circuits and Applying PharmacogenomicsPharmacogenomics in Modern in Modern

Clinical PracticeClinical Practice

Stephen M. Stahl MD PhDUniversity of California San DiegoUniversity of California San Diego

andUniversity of Cambridge, UK

1

DisclosuresType Company

Consultant Advent; Alkermes; Arena;AstraZeneca; BioMarin; BoehringerIngelheim; Bristol-Myers Squibb; CeNeRx;Cypress; Lilly; Forest;Ingelheim; Bristol Myers Squibb; CeNeRx;Cypress; Lilly; Forest; GenOmind, Janssen; Jazz; Labopharm; Lundbeck; Merck; Neuronetics; Novartis; Ono; Orexigen; Otsuka; Pamlab; Pfizer; Rexahn; Roche; Royalty; Servier; Shire; Solvay; Sunovion; V lValeant

Grant/Research Support

AstraZeneca,Cenerex,Lilly,Forest,GenOmind,Merck,Neuronetics,PamLab,Pfizer,Roche,Servier,Shire,Sunovion, Torrent

Speaker’s Bureau

Arbor Scientia,Astra Zeneca,Lilly,Forest,J & J,Merck, N i Ed ti I tit t Pfi S i d S iBureau Neuroscience Education Institute,Pfizer,Servier and Sunovion

Shareholder Neuroscience Education Institute

Obj tiObj ti•• To discuss modern formulations for the role of genetics inTo discuss modern formulations for the role of genetics in

ObjectivesObjectivesTo discuss modern formulations for the role of genetics in To discuss modern formulations for the role of genetics in psychiatric disorders, i.e. “nature”psychiatric disorders, i.e. “nature”

•• To show that environmental stress also converges on the To show that environmental stress also converges on the expression of genes, via epigenetic mechanisms, i.e., expression of genes, via epigenetic mechanisms, i.e., “nurture “nurture

T d t t h 21T d t t h 21stst t t l h ltht t l h lth•• To demonstrate how a 21To demonstrate how a 21stst century mental health century mental health professional puts this all together to make diagnoses and professional puts this all together to make diagnoses and to select psychopharmacologic treatments to select psychopharmacologic treatments p y p gp y p g

Psychiatric DisordersPsychiatric Disorders

• Psychiatric disorders are categorical collections of y gsymptoms chosen by a committee of experts

• Psychiatric disorders are revised periodically by the DSM (Diagnostic and Statistical Manual of the American Psychiatric Association)

Ps chiatric disorders are descripti e and reliable b t not• Psychiatric disorders are descriptive and reliable but not predictive of treatment response nor linked to neurobiology

• Psychiatric disorders are not diseases

Symptoms and Psychiatric DisordersSymptoms and Psychiatric Disorders

Symptoms and Psychiatric DisordersSymptoms and Psychiatric Disorders

• Each psychiatric disorder is likely to represent many diseases (maybe hundreds)

• Psychiatric symptoms correlate somewhat with lf ti i b i i itmalfunctioning brain circuits

• Psychiatric disorders do not correlate well with genotype biosignatures or brain circuitsgenotype, biosignatures or brain circuits

• Thus, the current diagnostic strategy is to attempt to link symptom domains that cut across psychiatric disorderssymptom domains that cut across psychiatric disorders first to inefficient information processing in specific brain circuits and eventually to genes regulating those circuits

orde

r

rder

DH

D

essi

ve d

iso

xiet

y di

sor

goric

al/A

D

maj

or d

epre

raliz

ed a

n

DS

M c

ateg

egor

ical

/m

rical

/gen

er D

DS

M c

ate

SM

cat

egor

RDoC dimensional/cognitive symptoms

DS RDoC dimensional/cognitive symptoms

RDoC dimensional/arousal/regulatory symptoms

Psychiatric Symptoms are Dimensional, Cutting Across Many Psychiatric DisordersAcross Many Psychiatric Disorders

Five Symptom Domains across psychiatric conditions searching for their underlying circuits and genes g y g g

(Research Domain Criteria RDoC of NIMH)

Social Processes Social Processes

• social cognition and social behaviors

Cognitive Systems Cognitive Systems

• attention, perception, working memory

Positive Valence Systemsy

• reward, appetitive behaviors

Negative Valence Systems

• depression, defeat, loss

Arousal-regulatory

• activity, sleep, rhythms

Circuits and SymptomsCircuits and SymptomsCircuits and SymptomsCircuits and Symptoms

What is the topographical distribution of What is the topographical distribution of f ti d th f t ti if ti d th f t ti ifunction and thus of symptom generation in function and thus of symptom generation in

the brain?the brain?

Overlap of MDD and Anxiety Disorders

fatigue

concentration

fatiguepsychomotor

sleepguilt/

worthlessness

dep’dmood Interest/

pleasurephobic

avoidance

panic attacks

anxietyworry

suicidalityappetite/weightirritability muscle

tension

compul-sions

avoidance

major depressivedisorderanxiety

disorders

14-1

positive symptoms negative

symptoms

schizophreniaaffective

symptoms cognitiveaggressivesymptoms

symptoms

9-5

Match Each Symptom to HypotheticallyMalfunctioning Brain Circuits

mesocortical/prefrontal cortexmesolimbic

positive symptoms

negative t

nucleus accumbensreward circuits

affective

symptoms symptoms

aggressiveaffectivesymptoms cognitive

symptoms

aggressivesymptoms

dorsolateralprefrontal cortex

amygdalaorbito-

ventromedialprefrontal cortex

9-12

amygdalaorbitofrontal cortex

ADHD: Deconstruct the Syndrome into DSM-V Diagnostic Symptoms

ADHD

inattentive symptoms

selectiveattention

sustained attentionproblem solving

hyperactive impulsive ypsymptoms

psymptoms

17-1

dorsal ACC DLPFC

selectiveattention

sustained attentionproblem solving

impulsive symptoms

hyperactive symptoms

prefrontal motor

orbitalfrontal

17-2

motor cortex

frontal cortex

Psychiatric “Stress” TestingPsychiatric “Stress” Testing

Putting a load on a brain circuit and becoming Putting a load on a brain circuit and becoming a CNSa CNS--I (Central Nervous System Investigator)I (Central Nervous System Investigator)a CNSa CNS I (Central Nervous System Investigator)I (Central Nervous System Investigator)

Cortical pyramidal neurons and neurotransmitters: more is not always bettery

onal

mid

al n

euro

nctio

ning

receptor stimulation

pyra

m fu

receptor stimulation

7-26

N-Back Test

ti lstimulus

response

0-back 1 4 2 3

1-back none 1 4 2

8-8

Hypothetical CSTC Loop for Executive FunctionsDLPFC Striatum Thalamus DLPFC

7-17

The Stroop Task

right answer = “red”

Blue

Red

wrong answer = “blue”

Red

Orange

RedRed

Green

Green

8-14

Dorsal ACC Bottom of Striatum Thalamus ACC

Hypothetical CSTC Loop for Attention

7-18

Processing Fearful Faces

“match the emotion”

8-11

Subgenual ACC Nucleus Accumbens Thalamus Cortex

Hypothetical CSTC Loop for “Emotions”

7-19

Hypothetical CSTC Loop for Impulsivity/Compulsivity

OFC B tt f C d t Th l OFCOFC Bottom of Caudate Thalamus OFC

7-20

Genes and Psychiatric DisordersGenes and Psychiatric Disorders

Classical Theory: Genes Cause Mental Illness

hypothetical mental illness geneg

abnormal gene product causes

neuronal malfunction

mental illness

6-2

mental illness

Symptom Endophenotype Model: Genes Cause Psychiatric Symptoms, Behaviors,

Personalities and Temperamentshypothetical gene for

a symptom,b h i lit

Personalities and Temperaments

behavior, personality ortemperament

abnormal gene causesneuronal malfunction

b lhi t i

6-3

abnormal behavior

psychiatricsymptom personality temperament

Hypothetical Gene for Subtle Molecular Abnormalities

neuro-d l t

hypothetical gene for

btl

developmentserotonin

transportera subtle

molecularabnormality

axonal and dendritic protein

synthesis and internaland internal

transport

signalsignal transduction

pathway

synaptic plasticity

6-4

y p p ymachinery

enzymes for monoamine degradation

Genes and Psychiatric Disorders

• There is no known gene for any psychiatric disorder, nor isThere is no known gene for any psychiatric disorder, nor is there ever expected to be one found

• Genes do not code for psychiatric disorders

• Genes do not code for psychiatric symptoms

• Genes code for proteins and epigenetic regulators, many p p g g , yof which regulate the efficiency of information processing in brain circuits, which can be visualized with neuroimaging techniquestechniques

• Thus, psychiatric research is attempting to link circuits upstream to treatment response and downstream toupstream to treatment response and downstream to regulatory genes

Hypothetical Path from Gene to Behavior

genotype

subtle molecular abnormality

abnormal informationprocessing

(biological endophenotype)

behavior with complexfunctional interactions

and emergent phenomena( )

6-5

(symptom endophenotype)

Hypothetical Path from Genes via Molecules, Circuits andInformation Processing to Symptoms, Syndromes, and Mental Illnesses

risk gene 1 risk gene 2 risk gene 3

altered alteredaltered enzymefor monoamine

degradation

alteredsynapticplasticity

machinery

altereddevelopmentin prefrontal

cortex

biological biological A B

overactivationnormalbaselineg

endophenotypeg

endophenotypeA Bbaseline

hypoactivation

tisymptom symptomh t

6-6

executive dysfunction delusionssymptom

endophenotypesymptom

endophenotypeschizophrenia

phenotype

N t N t ?N t N t ?Nature or Nurture?Nature or Nurture?

Genes or the Environment?Genes or the Environment?Genes or the Environment?Genes or the Environment?

Genetics or Genetics or EpigeneticsEpigenetics??

Model of “Diabolical Learning”

A B C

tibiological

endophenotype X Y Z

time

inadequate or no

treatmentunprovoked,

decompensation with either overactivation or circuit breakdown

treatment

symptomendophenotype

orphenotype psychiatric symptom of a psychiatric

disorder( d b i i d d

8-6A

(e.g., drug abuse, pain, panic, depressed mood, insomnia)

Model of “Diabolical Learning”

A B C

timebiological

endophenotype X Y Z

time

inadequate or no

treatment

decompensation and circuit breakdown worsening

treatment

symptomendophenotype

orphenotype symptoms worsen

or relapse

8-6B

Model of “Diabolical Learning”

A B C

biological endophenotype X Y Z

further plastic changes in circuitry that facilitate maladaptive information

processing, which is difficult to reversep g,

symptomendophenotype

orphenotype new symptoms

or treatment resistance

8-6C

Normal Functioning of a Circuit:Normal Activation Under Stress

normal genes

bad childhood divorce

virus org

life events

virus or toxin

overactivationnormal overactivationnormalbaselinehypoactivation

circuit

normal activation

6-7normal phenotype

Genetically Biased Circuit but No Symptoms:able to compensate for genetically inefficient

information processing by overactivationrisk gene

divorceinformation processing by overactivation

single life event stressor

“biased” circuit

overactivationnormalbaseline

overactivation

baselinehypoactivation

inefficient informationprocessing

6-8

normal phenotype

Stress-Diathesis Model of Psychiatric Symptoms:too many genetic biases combined with too many stressors results in

psychiatric symptoms

risk gene

risk gene

risk

risk gene bad childhood divorce

virus or

psychiatric symptoms

ggene

multiple life events

virus or toxin

“biased” diathesis stress overactivation

normalb licircuit

hypoactivation unsuccessful

baselinehypoactivation

hypoactivationwith

malfunction

unsuccessfulcompensation

6-9psychiatric symptoms

Stress-Diathesis Model Part 1: no risk gene, normal function

mild stressor severe stressor

no stressor normal function normal functionno stressor normal function normal function

6-10

Stress-Diathesis Model Part 2: one risk gene, normal function

mild stressor severe stressorrisk gene

normal function normal functionno stressor normal function normal function no stressor

6-11

Stress-Diathesis Model Part 3: two risk genes, slowing of function but compensation and no breakdown

mild stressor severe stressorrisk gene 1 risk

gene 2gene 2

normal function normal functionno stressor normal function normal function no stressor

6-12

Stress-Diathesis Model Part 4: multiple risk genes, slowing of function with mild stressor, but decompensation and breakdown with severe stressorbut decompensation and breakdown with severe stressor

mild stressor severe stressorrisk gene

1

risk gene 2

risk gene 3

risk gene 3

1

slowing of function breakdownno stressor slowing of function breakdownno stressor

6-13

Hypothetical Path Linking Circuits to Symptom Domains and to Biomarkers

symptom domain

DSM syndrome clinical subtype/treatment response

abnormal informationprocessing (neuroimaging)

y p

gene expression

molecular abnormality (biomarker signature)

gene expression

epigenetic genetic

Genetics and Psychiatric TreatmentsGenetics and Psychiatric Treatments

Genes and Psychiatric TreatmentsGenes and Psychiatric Treatments

• Markers for psychotropic drug metabolism are well established (pharmacokinetics)

• Low drug levels and lack of efficacy

• High drug levels and side effects

• Pharmacodynamics

• Unmet need for predictors of responses to specific h t i dpsychotropic drugs

Pathways of genetic variability can lead to an adverse drug reaction or to an inadequate response g q p

Genetic Polymorphisms

Pharmacokinetic Pharmacodynamic

Ab ti ExcretionImmune System

ReceptorsAbsorption Excretion Receptors

Distribution Metabolism EnzymesIon Channels

Adapted from Pirmohamed, M. et al. Genetic susceptibility to adverse drug reactions. Trends in Pharmacological Sciences 22, 298-305.

Genes and Side Effects of Psychotropic Drugs

• Most psychotropic drug labels already contain references to genetic markers that recommend dosereferences to genetic markers that recommend dose adjustments to mitigate side effects or drug interactions

• However these are not commonly usedHowever, these are not commonly used• Expensive/reimbursement

• Availability, delayAvailability, delay

• Not current standard of care/best practices

• If anything, phenotyping with therapeutic drug levels is more common than genotyping

• Most side effects are nuisances (nausea, insomnia, sedation) rather than dangerous (agranulocytosissedation) rather than dangerous (agranulocytosis, tardive dyskinesia), so current practice is trial and error, not genotyping

Safety/tolerability Genomic Markers Biomarkers That May Require Dose Adjustments or at Risk for Drug Interactions

Antidepressant Enzymes responsible for biotransformation

Tricyclics (demethylation) CYP2C19, CYP1A2, CYP3A4

Fluoxetine CYP2D6, CYP2C9, CYP2C19, CYP3A4

Paroxetine CYP2D6, CYP3A4,

Fluvoxamine CYP1A2, CYP2D6

Sertraline CYP2C9, CYP2C19, CYP2D6, CYP3A4

Cit l CYP2C19 CYP2D6 CYP3A4Citalopram CYP2C19, CYP2D6, CYP3A4

Escitalopram CYP2C19, CYP2D6, CYP3A4

Venlafaxine CYP2D6, CYP3A4

Duloxetine CYP2D6, CYP1A2

Mirtazapine CYP2D6, CYP1A2, CYP3A4

Trazadone CYP3A4Trazadone CYP3A4

Buproprion CYP2B6

Genes and Therapeutic Response to Psychotropic Drugsy p g

• No current psychotropic drug is labeled with reference t ti k th t li k d t h thto genetic markers that are linked to whether an individual is more likely to respond/not respond

• Trial and error is the current practice• Trial and error is the current practice

• However, there is a premium on early response in depression, as the longer it takes to find an effectivedepression, as the longer it takes to find an effective treatment, the less likely it is to work and to keep working

S d C l iS d C l iSummary and ConclusionsSummary and Conclusions

•• Genes bestow risk for mental illness, and many genes Genes bestow risk for mental illness, and many genes must “conspire” in order to produce risk for the majormust “conspire” in order to produce risk for the majormust conspire in order to produce risk for the major must conspire in order to produce risk for the major mental mental disordersdisorders

•• Environmental stressors converge upon the expression of Environmental stressors converge upon the expression of g p pg p pgenes, and via epigenetic mechanisms, cause the good or genes, and via epigenetic mechanisms, cause the good or bad expression of normal genes, i.e., “nurturebad expression of normal genes, i.e., “nurture””

S dS d C l i (2)C l i (2) AA 2121stst centurycentury mental health professional putsmental health professional puts this allthis all

Summary and Summary and Conclusions (2)Conclusions (2)A A 2121 century century mental health professional puts mental health professional puts this all this all together together byby

FirstFirst, constructing a , constructing a diagnosisdiagnosisss , co s uc g a, co s uc g a d ag os sd ag os s

ThenThen, deconstructing the diagnosis into its component , deconstructing the diagnosis into its component symptomssymptomsy py p

NextNext, matching each symptom with its hypothetically , matching each symptom with its hypothetically malfunctioning brain malfunctioning brain circuitcircuitgg

FinallyFinally, selecting treatments that change neurotransmitters , selecting treatments that change neurotransmitters in that circuit to improve the efficiency of information in that in that circuit to improve the efficiency of information in that p yp ycircuit and thus reduce circuit and thus reduce symptomssymptoms

Special Issues in the Long Term Care Patient with Neurobehavioral

Disorders John W. Daly MD Clinical Professor

UCSD Geriatric Medicine Medical Director SOCARE

Number of persons over 65 in US

0

10

20

30

40

50

60

70

1900 1920 1940 1960 1980 2000 2020

Year

Mill

ions Over 85

Over 65

Percent of community elderly living alone

0

10

20

30

40

50

60

65-74 75-84 85+

malefemale

Prevalence of at least 1 ADL or IADL difficulty among older individuals in the community

0

10

20

30

40

50

60

65-69 70-74 75-79 80-84 85+

malefemale

Nursing home use increases with age

0

5

10

15

20

25

65-74 75-84 85+

malefemale

Psychiatric illness in nursing home

• May affect as much as 80 to 90 % of nursing home population

• Most common illness is dementia, affecting 50 to 75% – Rover, German et al 1990 – Parmalee, et al 1992

Long term care environments

• Skilled nursing Care • Custodial nursing care • Residential care for the elderly **

– Assisted living – Board and care (I’m bored and they don’t care)

• Residential Care for dementia ** – ** not covered by Medicare, Medical, Medicaid

Short stay

1-6 months

Long stay

6 months or more

Hospice

Terminal

illness

Rehab

and

Sub-acute care

Primary

Cognitive

impaired

Primary Physical impaired

Both

All long term care patients

Special features of long term care

• Patient population • Co-morbid conditions • Medical information • Poly-pharmacy • Resource availability

The patient in long term care

• Dependant for ADL’s • Impaired mobility • Sensory impairment • Impaired communication • Impaired cognition

Long term care admission

Impaired mobility Behavioral or

cognitive disorder

ADL dependence

Lack of caregiver support Incontinence

Factors leading to long term care placement

Pain

Long term care

Acute care hospital

Home

Other long term care facility

Other: ER, APS

Sources of LTC admission

Dangerous combinations

• Impaired mobility and incontinence = – Falls and fractures

• Cognitive and motor impairment = – Dehydration, malnutrition, falls and fractures

• Sensory and cognitive impairment = – Falls, fractures, depression, delusions and

agitation

Co-morbidity in LTC

• Previously diagnosed conditions • Previously undiagnosed conditions • Previously misdiagnosed conditions • New conditions developing after admission

to LTC

Co-morbidity in patients with psychiatric illness

• Chart review of admissions to the Senior Behavioral Medicine unit at UCSD ( an inpatient Geriatric Psychiatry facility) revealed that 40% of all admissions had previously unrecognized and untreated medical conditions.

Dr. John’s first rule in evaluation of the LTC patient

Do not assume that the list of diagnosis on the admission H & P is

complete or even accurate

Barriers to accurate medical information

• Patient unable to provide history

• Incomplete medical records in LTC facilities

• Family with limited or erroneous understanding of the history

• Many providers and sub-specialty fragmentation of the history

• Doctor shopping and “shopping list” medical records

Adverse drug reactions (ADRs) in the elderly

• 10% to 17% of acute geriatric admissions are for ADRs

• In Outpatients – 18% 0f elderly outpatients suffer ADRs – 35% of high risk (i.e. those taking 5 or more

medications) suffer ADRs

Classes of drugs that contribute to delirium

• Analgesics &

Hypnotics • Psychotropics • Anticholinergics • Antiparkinsonian • Antihistamines

• Antihypertensives Cardiovascular agents

• Hypoglycemics • Steroids • Antimicrobials • Others/ idiosyncratic

This image cannot currently be displayed.

Physician measures to evaluate drug appropriateness

• Strive to confirm the diagnosis • Evaluate thoroughly to identify conditions:

– That could benefit from therapy – Be adversely affected by drug therapy – Influence the efficacy of drug therapy

• Manage medical conditions without drugs if possible, but remember advanced age in itself should never be considered a contraindication to potential beneficial therapy

General recommendations

• Simplify drug regimen • Evaluate need for each drug taken • With new drug start low, go slow • Use a few drugs well, rather than many

drugs poorly • Titrate based on response • Close attention to adverse reactions

The risk of Adverse drug reactions are much higher in patients with

dementia • We just don’t know how much higher • Adverse drug reactions can contribute to all

of the complications of advanced dementia

The cognitively impaired patient in LTC

Dementia or delirium?

Delirium and mortality

• 6 month mortality of elderly patients admitted to post acute care facility – With delirium: 25.0% – With sub-syndrome delirium: 18.3% – Without delirium: 5.7%

• (Marcantonio et al. JAGS #6,June 2005:963-9)

Causes of delirium

• Metabolic • Infection • Cardiovascular • Cerebral vascular • Pulmonary Disease • Drugs / intoxication • Anemia • Trauma

• Fecal impaction • Urinary retention • Acute psychosis • Altered or impaired

sensory input • Hypo or hyperthermia

Classes of drugs that contribute to delirium

• Analgesics &

Hypnotics • Psychotropics • Anticholinergics • Antiparkinsonian • Antihistamines

• Antihypertensives Cardiovascular agents

• Hypoglycemics • Steroids • Antimicrobials • Others

This image cannot currently be displayed.

The Medical History

• Existing and past medical illness may manifest as an apparent cognitive decline

• The presence of cognitive impairment may mask the symptoms of other underlying medical conditions

The Clinical Management of Moderate and Severe Dementia

Late stage dementia care guidelines

• Few clinical studies and there is little that is evidence based to guide clinical care.

• There are no well established guidelines • Recommendations must rely on the

observations and experiences of “seasoned” clinicians (experts in the field)

Complications of late stage dementia

• Behavioral disturbance • Gait disorder and falls • Weight loss and cachexia • Co-morbid chronic illness • New onset acute medical illness

Falls and Late Stage Dementia

• Individuals with dementia have an increased risk for falls and fractures – Fracture rate 3 X greater in AD than age and sex

adjusted general population – Buchner and Larson, JAMA 257:11, 1987

• Many variables are involved in the risk for falling in dementia patients – Co-existing illness, adverse drug reactions, gender,

dementia stage & type, gait apraxia, environment

Co-existing conditions contributing to gait disorder in dementia

• Adverse drug reaction • Orthopedic abnormalities • Muscle wasting and weakness • Cerebellar, basal ganglion or vestibular

deficits • Peripheral neuropathy • Peripheral vascular disease

Common chronic conditions that increase fall risk

• Hypertension • Atrial Fibrillation • Congestive heart failure • Diabetes • Urinary incontinence

Drugs that contribute to fall risk

• Diuretics • Antihypertensives • Antiarrhythmics • Antipsychotics • Antidepressants • Benzodiazepams • Hypoglycemic agents • Drug-drug interactions

• Cholinesterase inhibitors? (bradycardia)

• Anticonvulsants • Anticholinergics • Hypnotics • Antihistamines • Opiates • Others (idiosyncratic)

Weight loss and dementia

Progressive weight loss is one of the hallmarks of end-stage dementia

Advanced dementia and weight loss

• Accelerated weight loss is common in advanced dementia • There is a loss of skeletal muscle mass and decreased fat

free mass • Association between low body weight and atrophy of

mesial cortex • There is no compelling evidence for a hyper-metabolic

syndrome in dementia • Decreased active energy expenditure is associated with

decreased energy intake – Review by Poehlman and Dvorak Am J Clin Nutr 2000:71 (suppl)

Strategies to ameliorate weight loss in dementia

• Eliminate unnecessary or appetite suppressing medications (poly-pharmacy)

• Energy dense foods • Assisted feeding • Increase physical activity

– Increase of energy expenditure leads to increase of energy intake

– May help decrease sarcopenia

Drugs that can contribute to weight loss

• Statins • Cholinesterase

inhibitors • Antibiotics • Opiates • NSAIDs • Digoxin

• Sedatives and hypnotics

• Antidepressants – SSRIs – Amitriptyline

• Anticholinergics • Antipsychotics

So what about tube feedings in dementia patients

• Review of the evidence showed no evidence of benefit for patients with dementia – No benefit for: survival, pneumonia, pressure sores, or

function – Finucane et al. JAMA 1999:282(14)

• Worse outcomes for dementia patients – Mortality 54%/1 month 90%/1 yr dementia – VS 28%/1 month 63% /1yr non dementia

– Sanders et al. Amer Jour Gastroenterology 2000: 95(6)

Agitation and aggressiveness in late stage dementia

• Are common and have a significant adverse impact on care

• Most frequent reason for failure of care at home or for transfer from care facility to inpatient geriatric psychiatry unit

• Have numerous biologic and environmental triggers.

Antipsychotics and dementia

• Are commonly used to treat symptoms of psychosis and agitation in dementia

• Do not have FDA approval for use in dementia

• Recent review of the clinical trial evidence has questioned the efficacy and safety of these medications

The FDA and atypical antipsychotics

• Public health advisory for the use of all atypical antipsychotic medications in elderly patients with dementia – Data suggests an increased mortality mostly

from cardiac events or infections (pneumonia) – http://www.fda.gov/cder/drug/advisory/antipsy

chotics.htm

PRN medications in RCFE

• Every prescription and non-prescription PRN medication for which the licensee provides assistance must have a prescription including: – Specific symptoms which indicate need – Exact dosage – Minimum # of hours between doses – Maximum # of doses in 24 hour period

PRN medications rule 1

• If the resident’s physician has stated in writing that the resident is able to determine and communicate need for a prescription or non-prescription PRN medication, facility staff shall be permitted to administer

PRN medications rule 2

• If the resident’s physician has stated in writing that the resident is unable to determine his/her need for PRN med but can communicate symptoms staff may administer

PRN medications rule 3

• IF the resident is unable to determine need for a PRN med, and is unable to clearly communicate symptoms – Facility staff shall contact the resident’s physician prior

to each dose, describe the symptoms and receive direction to assist

– Date and time of each contact with physician and the directions shall be documented

– The date and time, dose and resident’s response shall be documented

PRN the take home message

• In general in a frail elderly individual with impairment of cognition and/or communication PRN medications are to be avoided!

• The preferred approach to symptom management is scheduled medication, with observation and documentation of target symptoms and/or potential medication side effects and regular schedule reevaluation (such as behavior or symptom mapping)

Problems with PRN medication use

• Inconsistent dosing – Variations with changes in staff (weekend and

night shift) • Overuse/ underuse • With brief episodic behaviors medication

frequently given after behavior has subsided • Decreased use of non pharmacological

measures

Medical conditions that cause or contribute to agitation in dementia

• Adverse drug reaction • Sensory impairment • Metabolic disorders • Infections • Dyspnea • Anemia

• Fecal impaction • Urinary retention • Pain

– Muscle-skeletal – Inflammatory – Visceral – Neuropathic

Pain is Special

• Can present as agitation, aggressiveness, depression, apathy or functional decline

• Difficult to recognize in a patient with impaired ability to communicate

• Advanced dementia may alter perception of pain • Presence of agitation or aggression may result in

an incomplete exam and failure to identify the source of pain

Dementia features that may contribute to agitation

• Agnosia: – Misperceptions and misinterpretation of the

environment can cause fear response • Aphasia:

– Inability to communicate or understand leads to frustration response

• Apraxia: – Difficulty with common automatic daily tasks also

causes frustration and anger

Environmental triggers to agitation and aggression

• Noisy, chaotic or confusing environment • New environment or situation • Confinement or restraint • Staff or caregiver response

– Attempts to restrain or confine patient – Confrontational approach – Loud, threatening or angry voice – Facial expressions

Non-drug interventions for agitation

• Redirection away from focus of agitation – Engagement in conversation or activity – Walk with me , talk with me – Avoid confrontation – Be flexible, creative and innovative

• Behavior mapping – To identify triggers and patterns of agitation

• Quiet rooms – Music, mood lighting, comfy chair

The “General”

• A retired military man with advanced dementia living in Alzheimer’s care community. He is non-verbal with gait apraxia and is mobile with a wheelchair. He feeds himself with assistance and responds non-verbally with the staff.

The General: a change in scene

• He has been relatively stable with slow progressive decline at the community.

• His baseline behavior is that he constantly hums to himself and smiles when addressed.

• Because his wife is suffering from a terminal illness he is moved to a facility closer to her.

The General’s return 6 month’s later

• The original care center is notified by his children that they are bringing him back and that he is dying. His wife has died from her illness.

• On admission is apathetic, withdrawn, unable to feed himself and has pneumonia

• He Is NOT Humming

A case of over reaction to the symptoms

• The new facility had interpreted his constant humming as a target symptom of agitation.

• On his transfer back he was on an atypical antipsychotic, an anticonvulsant and a benzodiazepam.

• These medications were discontinued, he was given an oral antibiotic and in 2 weeks was humming, eating and smiling.

A pragmatic approach to behavioral symptoms in late stage dementia

• Evaluate thoroughly for underlying cause or trigger for behavior

• Focus on those symptoms that place the patient or others at risk

• Do not treat trivial or annoyance behaviors • Try non-drug interventions first, and

educate staff or caregiver

Dementia and chronic illness

• Diabetes • Hypertension • Congestive heart failure • Prostate disease

Diabetes

• With dementia progression, weight loss and poor oral intake there is an increased risk for hypoglycemia

• Glycemic control may need to be loosened

• The patient with hyperglycemia and poor fluid intake is at increased risk for dehydration and hyper-osmolality syndrome

• But not too loose

Hypertension

• Increased risk for orthostatic hypotension and falls, especially if antipsychotic or antidepressant is started

• Diuretics may increase risk for dehydration, orthostatic hypotension and falls

• Combination of beta blocker and cholinesterase inhibitor may cause significant bradycardia

CHF and dementia

• Agitation is a common first symptom of CHF decompensation

• Diuretics and poor fluid intake can cause dehydration

• Increased risk for hypotension with dementia progression

Prostate disease and dementia

• Urinary retention commonly presents as increased agitation.

• Many antidepressants and antipsychotics increase the risk of urinary retention

• Increased risk for urinary tract infections

A case of impaired communication

• 85 y/o male with moderate dementia that presented initially as primary progressive aphasia

• Pt developed increased agitation and pacing at home, psychiatrist consulted and trazodone started for agitation.

• Agitation worsened and risperidone added • Pt experienced functional decline, more agitated,

urinating in inappropriate places (potted plants)

The problem and the solution

• Patient admitted to Senior Behavioral Health Unit • Physical exam: markedly distended bladder • Foley catheter placed and 2 liters of urine obtained • Agitation resolved. Medications discontinued. Pt

discharged with Urology follow-up

Special considerations in LTC

• Safety versus autonomy • Quality of life, comfort care, hospice care • Hospitalization, emergency room use • Competence, capacity, and dignity

Advanced Directives and Long Term Care

• Resuscitation status, power of attorney and decision making capacity are assessed and documented at time of admission

• For individuals who are a “do not resuscitate” status a pre-hospital DNR form must be completed and displayed in the chart

POLST

• Used in most RCFE facilities • Addresses the patient preferences for

resuscitation status, IV fluid or feeding tube use, antibiotic use and hospitalization

• Provides easy to access guidance for decision making by covering physicians

Dementia and hospice care

• Dementia is a progressive neurodegenerative condition that is invariably fatal

• The end stage of dementia is often a protracted course of functional impairment, and significant suffering

• Hospice and palliative care services are often underutilized for dementia patients

Barriers to hospice care for dementia

• Difficulty in predicting the course of end stage disease: “six month prognosis”

• Misconception that “one does not die of dementia” (7th leading cause of death in US)

• Physician lack of awareness of hospice services for dementia

Hospice care and dementia

• Is appropriate, but is underutilized • Needs different criteria for implementation • Perhaps palliative care should be started

sooner in late stage dementia given the course of protracted decline

• There is a need for more research into appropriate modalities to alleviate suffering in late stage dementia

Summary: the harsh reality

• Until there is a treatment that alters the progression of Alzheimer’s Disease and other dementias there will be an increasing number of late stage cases

• Very little evidence based guidance exists for appropriate treatment standards and practice

• There has been a failure of health care policy agencies at all levels to develop a strategic plan to address the growing need for care

Sleep Disorders in the Older Adult

Sonia Ancoli-Israel, Ph.D.

Professor Emeritus of Psychiatry and Medicine, UCSD

Director, Gillin Sleep & Chronomedicine Research Center

Director of Education, UCSD Sleep Medicine Center

VA Center of Excellence for Stress and Mental Health (CESAMH)

Sonia Ancoli-Israel Disclosures

Consultant/Scientific Advisory Board: Astra Zeneca, Ferring Pharmaceuticals Inc.,

GlaxoSmithKline, Hypnocore, Johnson & Johnson, Merck, NeuroVigil, Inc., OrphagenPharmaceuticals, Pfizer, Philips, Purdue PharmaLP, sanofi-aventis,

Reported Hours Slept Older vs. Younger American Adults

2003 NSF Sleep in America Poll

Changes in Sleep with Age

Meta-analytic review of 65 sleep studies in healthy persons3557 total subjects aged 5-102 years

Most age-related sleep changes occur in early and mid-years of human life span

In healthy older adults:Sleep remains relatively constant from age 60 to

mid-90sExcept for SE which decreases

Ohayon MM et al. Sleep. 2004, 27:1255-1273.

Rec

ordi

ng T

ime

(%)

Slow Wave Sleep

0

5

10

15

20

25

16-25 26-35 36-50 51-60 61-70 71-83

Van Cauter E et al. JAMA. 2000;284:861-868.

Changes with Age: Sleep Efficiency

Age

100

90

80

70

6010 20 30 40 50 60 70

MenWomen

Modified from Ohayon et al. Sleep 2004, 27:1255-1273

Sleep disturbance and cognition in older women (n=2932 women, mean age 83.5 years)

Objectively measured (5-days actigraphy) disturbed sleep was consistently related to poorer cognition,

Blackwell, Yaffe, Ancoli-Israel et al, J Gerontol: MED SCI, 2006, 61A(4):405–410

MMSE<26 Trails B >278s P-value

SE<70% 1.61

(95% CI 1.20–2.16)

1.96

(95% CI 1.43–2.67)

<0.05

Higher sleep latency (30m)

1.23

(95% CI 1.13–1.33)

1.13

(95% CI 1.04–1.24)

<0.05

Higher WASO (30m)

1.15

(95% CI 1.06–1.23)

1.24

(95% CI 1.15–1.34)

<0.05

All analyses adjusted for age, race, depression, education, body mass index, health status, history of stroke, history of hypertension, functional status, smoking, alcohol use, caffeine, antidepressant use, and physical activity.

Sleep disturbance and depression in older men (MrOS sleep study; n=3051)

Paudel et al, J Am Geriatr Soc. 2008 Jul;56(7):1228-35

Normal)

(n=2310)

Depressive symptoms

(n=537)

Depression

(n=204)

P-value

Subjective (PSQI)

Pittsburgh Sleep Quality Index >5

1.0

(referent)

2.06

(95% CI 1.67-2.55)

3.68

(95% CI 2.54-5.33)

<0.001

Objective (5-days actigraphy)

Sleep latency >1 hour 1.0

(referent)

1.40 (1.03-1.90) 1.68 (1.08-2.61) 0.006

All analyses adjusted for age, clinic site, race, body mass index, living alone, alcohol intake, smoking status, cognitive impairment, physical activity, certain medical conditions, education, self-reported health status, IADL impairments, and use of antidepressants, benzodiazepines and non-benzodiazepine anxiolytic/hypnotics.

Depressive symptoms have a strong, graded association with subjective sleep disturbances and are moderately associated with objectively measured prolonged sleep latency

Summary of Study of Osteoporotic Fractures Study Results (n= 3,022)

A 30-40% increased risk of subsequent falls associated in older women withTST< 7 hours / nightSE 65%

An increased mortality risk in older women with TST< 5 hours / nightSE 65%>2 hour naps

After adjusting for race, age, BMI, medical conditions, depression, cognitive function, exercise, IADL, use of anti-depressant or benzodiazepine

Stone,K.L., Ewing,S.K., Lui,L.Y., Ensrud,K.E., Ancoli-Israel,S.,et al. JAGS 54:1177-1183, 2006; Stone,K.L., Ancoli-Israel,S., Blackwell,T., et al. Arch. Intern. Med. :168(16):1768-1775:2008

Consequences of Disturbed Sleep

Difficulty sustaining attention

Decreased physical function

Slowed response time

Difficulty with memory

Decreased performance

May all be misinterpreted as dementia

Ancoli-Israel S, Roth T. Sleep. 1999;22(suppl 2):S347-S353; Ancoli-Israel, 2000, Sleep, 23 (suppl), S23 - S30.

Insomnia Complaints Prevalence Within Elderly (n=9282)

Perc

ent

Foley, et al., Sleep, 1995, 18:425-432

Chronic sleep disturbances primarily associated with indications of poor health (depressed mood, respiratory symptoms, fair to poor health, and physical disability).

Incidence of Insomnia in the Elderly

Of the 2000 survivors with chronic insomnia at baseline, about 50% had no symptoms at follow-upImproved self-perceived health associated with

discontinuation of insomnia symptoms

Foley et al concluded:“…these data do not support a model of incident

insomnia caused by the aging process per se.”

Foley D et al. Sleep. 1999;22:S366-372.

Factors Affecting Ability to Sleep in the Elderly

Medical illness

Medications/polypharmacy

Circadian rhythm disturbances

Primary sleep disorders

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000:597-661.

Many Medical Conditions Disturb Sleep

Hauri PJ. Clin Chest Med. 1998;19:157-168; Ancoli-Israel, 2000, Sleep, 23 (suppl), S23 - S30

Headaches

Neurodegenerative Processes

Arthritic Pain

CAD/ CHFGI changes (GERD, Dyspepsia)

Benign prostatic hypertrophy & Nocturia

Orofacial Pain/ TMJ

Peripheral Neuropathy with Pain

COPD

Psychiatric disorders

Sleep Problems and Multiple Medical Conditions

Foley, Ancoli-Israel, Bitz, Walsh, J Psychosom Res. 2004, 56(5):497-502.

Medications and Substances Associated with Insomnia

AlcoholAcute useWithdrawal

Caffeine

Nicotine

AntidepressantsSSRISNRI, atypical

Corticosteroids

DecongestantsPhenylpropanolaminePseudoephedrine

β agonists, theophylline derivatives

β antagonists

Statins

Stimulants

Dopamine agonists

Any drug that crosses the blood brain barrier and affects a

neurotransmitter system may be associated with

insomnia

SSRI = Selective Serotonin Reuptake Inhibitor; SNRI = Serotonin and Norepinephrine Reuptake Inhibitor; Schweitzer, PPSM.

Hauri PJ. Insomnia. Clin Chest Med. 1998;19:157-168. A Special Report: Sleep Disturbance. Boston, MA: Harvard Medical School Health Publications Group; 1999.

Sleepy Go to bed

Wake up

Wake up

Sleepy–Go to bed

Sleepy–Go to bed

Wake up

18.00 21.00 24.00 3.00 6.00 9.00 12.00

Advanced phase

Standard phase

Delayed phase

Circadian Sleep Phases

Modified from Ancoli-Israel, All I Want is a Good Night’s Sleep, 1996.Modified from Ancoli-Israel, All I Want is a Good Night’s Sleep, 1996.

Time of Day

SDB Prevalence According to AgeMrOs (n=2911; age 76y)

26.4% had RDI>15; 60% had RDI>5 SHHS definitions for hypopnea

The prevalence of RDI>15 increased with increasing age quartile (p=0.005) SDB prevalence increased with

increasing age, from 22.8% (95% confidence interval (CI)519.7–26.2%) for those <72y to 30.1% (95% CI526.9–33.3%) for those >80y

The prevalence of RDI>5 did not increase with increasing age quartile (p=0.68)

Age

Mehra R et al. JAGS 55:1356–1364, 2007

Older women with SDB have an increased risk of developing cognitive impairment – Prospective Study

Compared with women without SDB (n=193), women with SDB (n=105; 35.2%) were more likely to develop MCI or dementia (31.1% [n=60] vs 44.8% [n=47]; adjusted OR, 1.85; 95% CI, 1.11-3.08)

Elevated SaO2 (>15 events/hour) and high % of TST (>7%) with apnea or hypopnea were associated with risk of developing MCI (AOR, 1.71 [95% CI, 1.04-2.83]) or dementia (AOR, 2.04 [95% CI, 1.10-3.78])

Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment

Yaffe, K et al. JAMA. 2011;306(6):613-619

SDB+EDS = Mortality Risk

Gooneratne NS; et al Sleep disordered breathing with excessive daytime sleepiness is a risk factor for mortality in older adults. SLEEP 2011;34(4):435-442.

The presence of SDB is an important risk factor for mortality from EDS in older adults. In the presence of SDB at AHI≥20, EDS was associated with an increased all-cause mortality risk in older adults, even when adjusting for other significant risk factors, such as prolonged sleep duration. In older patients who had SDB without EDS, or EDS without SDB, there was no increased all-cause mortality rate.

Treating Apnea in Alzheimer’s Disease

Patients with AD do show high amounts of SDB

Patients with AD can tolerate CPAPAverage number of hours (5 h) worn did

not differ from clinic patients

CPAP improved Reduced AHI, EDS; deepened sleep, improved

some aspects of cognitive function

Continued use of CPAP over six months slowed the cognitive deterioration and improved mood

Ancoli-Israel,S., et al JAGS. 2008, 56:2076-81; Cooke et al. J Clinical Sleep Medicine, 2009, 5(4): 305-309; Ayalon et al. AJGP 2006 14(2):176-80; Chong et al JAGS 2006 54(5):777-81

When to Treat Sleep Apnea in the Elderly?

The bottom line is that if the sleep apnea is associated with clinical symptoms, then it should be treated, regardless of the age of the patient.Excessive daytime sleepinessHypertensionCognitive dysfunctionNocturiaCardiac disease High levels of sleep-disordered breathing

Ancoli-Israel, Sleep Med Rev. 2007 Apr;11(2):83-5.

Treatment for OSA

CPAP/BiPAP

Weight loss

Body position

Oral appliances

Surgery

RBD Case ExampleA 60-year old surgeon began to punch and kick his wife and jump out of bed during nightmares of being attacked “by criminals, terrorists, and monsters who always tried to kill me.” Work-related stress was the presumed cause of his sleep disturbance, but the violent behaviors intensified despite retirement 3 years later. He sustained several head lacerations, and his wife once had a severe headache for 2 days after receiving an accidental blow to the ear. The proper diagnosis was established after 11 years. A prodrome of excessive limb and body jerking during sleep had been present for at least 33 years.

Principles and Practice of Sleep Medicine, 1994

Pharmacologic Treatment of RBDNeurological exam

Pharmacological TreatmentClonazepam* – effective in ~90% of patients0.25-0.5mg at bedtimeTolerance generally does not developDiscontinuation = immediate relapseMechanism of action unknown

Melatonin*One hour before bedtimestarting at 6mg; increasing to 12-15 mg

Behavioral treatment*off-label

Restless Legs Syndrome

Restless Legs Syndrome Feelings of “creepy/crawling”

sensations in legs Relieved only with movement Diagnosis made on history:

“When you try to relax in the evening or sleep at night, do you ever have unpleasant, restless feelings in your legs that can be relieved by walking or movement?”

Prevalence of RLS by Age

Age Group, Range in Years

Perc

ent w

ith R

LS

Ohayon MM and Roth T. J Psychosom Res. 2002;53:547-554. Phillips B et al. Arch Intern Med. 2000;160:2137-2141.Berger K et al. Arch Intern Med. 2000;164:196-202.Rothdach AJ et al. Neurology. 2000;54:1064-1068.Lavigne GJ and Montplaisir JY. Sleep. 1994;17:739-743.Ulfberg J et al. Mov Disord. 2001;16:1159-1163.

Ohayon MM and Roth T. J Psychosom Res. 2002;53:547-554. Phillips B et al. Arch Intern Med. 2000;160:2137-2141.Berger K et al. Arch Intern Med. 2000;164:196-202.Rothdach AJ et al. Neurology. 2000;54:1064-1068.Lavigne GJ and Montplaisir JY. Sleep. 1994;17:739-743.Ulfberg J et al. Mov Disord. 2001;16:1159-1163.

Treatment for RLS/PLMSDopamine Agonists

ropinirole (Requip) 0.5-4 mg Can be safely titrated up to 4 mg po 2 hours before bedtime

pramipexole (Mirapex) 0.125-.5 mgUsually 0.5 to 0.75 mg po 2 hours before bedtime is enough to

control RLS or PLMD

gabapentin enacarbil (Horizant) Extended-Release Tablets 600mg approved for moderate-severe RLS 600 mg once daily taken with food at about 5 PM; doubling dose

does gets no additional benefit compared with the 600-mg dose, but caused an increase in adverse reactions

levodopa/carbidopa (Sinemet) 25/100 *

Hening et al. Sleep. 2004;27:560-583; Littner et al. Sleep. 2004;27:557-559.

* off-label

Behavioral and Cognitive Therapies

Behavioral and cognitive-behavioral therapies (CBTs) have demonstrated efficacy in RCTs.

Found to be as effective as prescription medications are for brief treatment of chronic insomnia.

Moreover, there are indications that the beneficial effects of CBT, in contrast to those produced by medications, may last well beyond the termination of treatment.

There is no evidence that such treatment produces adverse effects, but thus far, there has been little, if any, study of this possibility.

NIH State of the Science Conference Statement Manifestations and Management of Chronic Insomnia in Adults. Sleep 28(9): 1049-1057, 2005

Behavioral and Pharmacologic Therapy Combined - Wake Time

Morin CM, et al. JAMA. 1999;281:991-999.

Placebo(n=20)

*CBT = cognitive behavioral therapy: stimulus control, sleep restriction, sleep hygiene, and cognitive therapy

Randomized, Controlled Trial: 78 Men and Women, Mean Age 65

CBT*(n= 18)

Temazepam(n=20)

Combined(n=20)

Min

utes

Pharmacological Treatment

There are currently ten medications approved by the FDA for treatment of insomnia. benzodiazepines e.g., estazolam, flurazepam, quazepam, temazepam, and

triazolam the more recently introduced agents that act as benzodiazepine

receptors but have a nonbenzodiazepine structure (BzRAs)e.g., zaleplon, zolpidem, eszopiclone, etc

Melatonin agonist ramelteon

Histamine antagonist doxepin

Choosing A Pharmacologic TherapyDo you have difficulty initiating or maintaining sleep (or both)?

How many hours can you devote to sleep or inactivity, after taking the medication?

Agent Initiates Sleep

Maintains Sleep

Sleep with limited opportunity

Required Inactivity

Eszopiclone (Lunesta) √ √ 8+ hours

Zaleplon (Sonata) √ √ 4 hours

Zolpidem (Ambien) √ 7-8 hours

Zolpidem MR (Ambien CR) √ √ 7-8 hours

Zolpidem sublingual (Edluar) √ 7-8 hours

Zolpidem oral spray (Zolpimist) √ 7-8 hours

Zolpidem sublinqual (Intermezzo) √ √ 4 hours

Ramelteon (Rozerem) √ -

Doxepin (Silenor) √ -

BzRAs - Conclusions from the NIH State-of-the-Science Insomnia Conference 2005

Results from clinical trials indicate that these agents are efficacious in the short-term management of insomnia

The frequency and severity of these adverse effects are much lower in the newer benzodiazepine receptor agonistsmost likely because these agents have shorter half-

lives.

NIH State of the Science Conference Statement Manifestations and Management of Chronic Insomnia in Adults. Sleep 28(9): 1049-1057, 2005

Anti-depressants

Trazodone has been shown to be effective for two weeks

Another antidepressant, doxepin, has been found to have beneficial effects on sleep for up to 4 weeks for individuals with insomnia.

Data on other antidepressants (e.g., amitriptyline and mirtazepine) in individuals with chronic insomnia are lacking.

All antidepressants have potentially significant adverse effects, raising concerns about the risk–benefit ratio.

NIH State of the Science Conference Statement Manifestations and Management of Chronic Insomnia in Adults. Sleep 28(9): 1049-1057, 2005

Other Sedating Medications

A number of other sedating medications have been used in the treatment of insomnia. barbiturates (e.g., phenobarbital) antipsychotics (e.g., quetiapine and olanzepine).

Studies demonstrating the usefulness of these medications for either short- or long-term management of insomnia are lacking.

Furthermore, all of these agents have significant risks, and thus their use in the treatment of chronic insomnia cannot be recommended.

NIH State of the Science Conference Statement Manifestations and Management of Chronic Insomnia in Adults. Sleep 28(9): 1049-1057, 2005

OTC Antihistamines (H1 Receptor Antagonists)

Antihistamines (H1 receptor antagonists, such as diphenhydramine) are the most commonly used OTC treatments for chronic insomnia,

there is no systematic evidence for efficacysignificant concerns about risks of these

medications.

NIH State of the Science Conference Statement Manifestations and Management of Chronic Insomnia in Adults. Sleep 28(9): 1049-1057, 2005

Diphenhydramine and other antihistamines(H1-Receptor Antagonists)

Adverse EffectsSedation, grogginessDry mouth, blurred

vision, urinary retentionPsychomotor

impairment, dizziness, incoordinationDeliriumRenal failure

Advantages Available OTC Low cost Perceived as “safer than sleeping pills”

DisadvantagesHypnotic dose not well definedTolerance within a week

Tips for Older Adults

Exercise

Limit naps to 1 per day for <30 minutes

Take a walk to increase light exposure

Check medications

Avoid alcohol, caffeine, nicotine

Limit liquids

Keep regular hoursAncoli-Israel, S. Geriatrics, 1997, 52:20-30

Summary of Key Points – The Bottom Line

1. It is not aging per se that results in poor sleep but rather all the things that go along with aging.

2. Whether or not need changes, the ability to sleep does change with age.

3. Poor sleep in the older adult is most often associated with medical and psychiatric illness, medication, circadian rhythm changes and primary sleep disorders.

4. No matter the age of the patient, sleep disorders should be treated if they are interfering with quality of life or if there is a medical risk associated with it.