Transplant Psychiatry Curley L. Bonds, MD Associate Professor & Chair Department of Psychiatry & Human Behavior Charles Drew University School of Medicine.

Transplant PsychiatryTransplant Psychiatry

Curley L. Bonds, MDCurley L. Bonds, MDAssociate Professor & ChairAssociate Professor & Chair

Department of Psychiatry & Human Department of Psychiatry & Human BehaviorBehavior

Charles Drew University School of Charles Drew University School of MedicineMedicine

Associate Clinical Professor & Vice-ChairAssociate Clinical Professor & Vice-ChairDepartment of PsychiatryDepartment of Psychiatry

David Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA

Overview

• Brief overview of solid organ transplantation• Rationale for psychosocial screening• Role of psychosocial screening• Predictive value of psychosocial assessment • Pre-operative and post-operative issues• Pharmacological aspects of cardiac

transplantation• Challenges for the Organ Transplant

Psychiatrist

Scope of Solid Organ Transplantation

• Kidney• Kidney/Pancreas• Liver• Heart • Lung• Small Bowel• Special Senses (Cornea, Cochlea,

etc.)• Limbs (Face, Hand)

History of Organ Transplantation

• First successful transplant: 1951 (kidney)

• First partial success: 1953 (kidney, patient survived 175 days)

• First twin-to-twin transplant: 1954 (patient survived until 1962)

Waiting List as of 1/21/07

94,759 Waiting list candidates

24,438 Transplants (January - October 2006)

12,395 Donors(January - October 2006)

UNOS website data

The Transplant Team

• Transplant Surgeon• Internists & Sub-specialists• Psychiatrist/Psychologist• Transplant Coordinators/Nurses• Social Worker• Ethicists/Pastoral Services• Community Members

Pre-Transplant Evaluation

• Psychosocial Assessment– Past Psychiatric History– Current psychiatric symptoms/illness– Psychotropic use– Substance use history– Social support– Cognitive evaluation– Understanding & Knowledge

Determining Transplant Candidacy

PsychPsych

So

cial

So

cial

BioBio

AssessmentAssessment

Biopsychosocial Screening

Suitability for Transplant

ComplianceSocial Supports

Understanding &Knowledge

Recipient’s History and Habits

The Transplant Patient

Biological, psychiatric and ethical issues in organ transplantation

Ed. By Paula Trzepacz & Andrea DiMartini

© Cambridge University Press 200

Rationale for Psychosocial Screening

• Learn whether the patient will be able to form collaborative relationships with team and comply with medical regimen

• Assess substance abuse history and recovery, and predict patient’s ability to maintain abstinence

• Help the team get to know the patient as a person to provide better care

Rationale for Psychosocial Screening

• To learn about the psychosocial needs of the patient and family, and plan for services during the waiting, recovery, and rehab phases of the transplant process

• To establish baseline measures of mental functioning to monitor post-op changes

Rationale for Psychosocial Screening

• Predict the recipient's ability to cope with the stresses of surgery

• Identify co-morbid mental illnesses and plan interventions for them

• Ensure adequate education and understanding/informed consent

Psychological evolution and assessment in patients

undergoing OHT

Triffaux, Wauthy, Bertrand et al.European Psychiatry 2001: 16: 180-5

Pre OHT Screening

• Twenty-two consecutive transplant candidates underwent psychiatric evaluation

• Patients completed multiple questionnaires during the waiting period, then at 1 and 6 months after OHT

Measures Employed

• Speilberger’s State-Trait Anxiety Inventory

• Beck Depression Inventory• Perceived Social Support Scale• Toronto Alexithymia Scale• Personal Reaction Inventory

Pre-operative pathology

• 41% (n=9) of patients had some DSM IV Axis I Diagnosis

• 18% (n=4) presented with an Axis II condition

Psychosocial Risk Factors for Noncompliance

• History of substance abuse• Age <30• Experiencing economic or psychosocial

stress

Surman 1992

Psychosocial Factors Associated with Poor Transplant Outcomes

• Poor social support• Psychiatric disorders likely to

compromise adequate postoperative compliance (affective disorders, psychosis, anxiety disorders, etc.)

• Self-destructive behaviors including nicotine, alcohol and drug abuse

Psychosocial Factors Associated with Poor Transplant Outcomes

• Poor compliance with medical treatment (combined with a continued failure to appreciate the necessity of change)

• Intractable maladaptive personality traits (such as oppositionality or counter-dependence)

Prognostic Factors for Substance Dependence and Abuse Recidivism

POSITIVE FACTORS• Stable living environment• Resources for abstinence• Recognition and

acceptance of dependence as a problem

• Absence of concurrent psychiatric disorders

• Compliance with post-transplant recommendations for addictions care

NEGATIVE FACTORS• Preexisting psychotic

disorder• Unstable character

disorder• Unremitting polydrug

abuse• Multiple failed attempts

at rehab• Social isolation

Evaluation Process

• >95% of US programs utilize some form of pre-transplant psychosocial evaluation process

• ~25% of US programs require formal psychological testing as part of the screening process

• In 1990, pre-operative screening rates were highest among OHT programs (23%) compared to liver and kidney program

Levinson & Olbrisch, 2000

Psychotic Disorders as a Contraindication to OHT at US Transplant Programs

AbsoluteContraindication

Relative Contraindication

Irrelevant

ActiveSchizophrenia

92.3% 5.1% 2.6%

ControlledSchizophrenia

33.3% 51.3% 15.4%

Levinson & Olbrisch, 2000

Affective Disorders as a Contraindication to OHT at US Transplant Centers

Absolute Contraindication

Relative Contraindication

Irrelevant

Current Affective Disorder

44.9% 47.4% 7.7%

Hx of Affective Disorder

5.1% 62.8% 32.1%

Levinson & Olbrisch, 2000

Suicidal Ideation/Attempts as a Contraindication to OHT at US Transplant Centers Absolute

Contraindication

Relative Contraindication

Irrelevant

Recent Suicide Attempt

51.3% 41.0% 7.7%

Distant Suicide Attempt

12.8% 64.1% 23.1%

Hx of Mult. Suicide Attempts

71.8% 24.4% 3.8%

Current SI 75.6% 17.9% 6.4%

Mental Retardation/IQ as a Contraindication to OHT at US Transplant Centers

Absolute Contraindication

RelativeContraindication

Irrelevant

MRIQ >70 25.6% 59.0% 15.4%

MRIQ <70 74.4% 19.2% 6.4%

Levinson & Olbrisch, 2000

Dementia as a Contraindication to OHT at US Transplant Centers

• Absolute contraindication: 71.8%• Relative contraindication: 23.1%• Irrelevant: 5.1%

Levinson & Olbrisch, 2000

Character Disorder as a Contraindication to OHT at US Transplant Centers

• Absolute contraindication: 14.1%• Relative contraindication: 62.8%• Irrelevant: 5.1%

Levinson & Olbrisch, 2000

Assessment Tools

• TERS - Transplant Evaluation Rating Scale

• PACT – Psychosocial Assessment of Candidates for Transplantation

Predictive Value of Pre-Op Assessment

Psychiatric Disorders and Outcome Following Cardiac Transplantation

Skotzko, et al., J. of Heart and Lung Transplantation, 1999

Predictive Value of Pre-Op Assessment

• 107 OHT recipients• Transplanted Jan. ’90 - Sept. ’91• Retrospective chart review• Medical outcomes measured:

1 year survivalrehospitalizationsinfectionsrejections

Predictive Value of Pre-Op Assessment

• Group I (n=25) Any Axis I Dx• Group II (n=82) No Axis I Dx

• Findings: No significant difference between Groups I and II at 1 year

• Implications

GuiltGuilt

Anx

iety

Anx

iety

Depression

Depression

Dis

abili

ty

Dis

abili

ty

WaitingWaiting

Pre-Operative Issues

UNOS Heart Allocation Policy

• Status 1A Pt requires: Continuous hemodynamic monitoring and cardiac or pulmonary assistance with one or more of the following:

- cont. IV or inotropes- left and/or right ventricular assist system- intraaortic balloon pump or ventilator for

pts<45- all pts < 6 months old

• Status 1BPt requires: a circulatory assist device or admission to an acute care hospital and continuous infusion of IV inotropes

UNOS Heart Allocation Policy

• Status 2APatient requires continuous infusion of IV inotropes

• Status 2BPatients needing a heart transplant but not meeting criteria for 1A, 1B or 2A

Pre-Operative Interventions

• Transplant Support Group• Internet/Online Support Groups• National Heart Association• Transplant Olympics• Individual Psychotherapy• Antidepressants/Anxiolytics

Body Image

Body Image

New

Med

s

New

Med

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Role Strain

Role Strain

Fina

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l

Fina

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l

RehabilitationRehabilitation

Post-Operative Issues

1st Three Years after OHT

• 191 OHT recipients were followed for 3 years:– Major Depressive Disorder

25.5%– Adjustment Disorders

20.8%– PTSD-T 17%– Any Disorder 38%

Dew, Kormos, et al Psychosomatics2000

Psychological Changes in the Recipient

• Castelnuovo-Tedesco– Expansion of body image– Incorporation of a non-ego ‘part object’ – Ambivalence towards a live-giving

object that can also be lethal

“This is the matrix in which one finds besides depression, blissful euphoria or paranoid dread.”

Ageism and Transplantation

• Most US Transplant Programs use age 65 as an automatic cut off for transplantation

• Medical data now shows that transcipients over 65 can do as well as younger patients

• Led to the Alternate Transplant List at UCLA

UCLA Experience

Subjects with Axis I Disorders vs Subjects with No Psychiatric Disorders*

3

24

19 19 19

2

24

29

44

20

0

5

10

15

20

25

30

35

40

45

50

Mortality 1 Year Rejection 1 Year Infection 2 Year Infection Readmissions

Pe

rce

nta

ge

Subjects with Axis I Disorders(N=21)

Subjects with No PsychiatricDisorders (N=31)

*p values insignificant

UCLA Alternate Transplant List

Subjects >65, Axis I Disorders vs No Psychiatric Disorders*

0

33

67 67

33

0

67

83 83

50

0

10

20

30

40

50

60

70

80

90

Mortality 1 Year Rejection 1 Year Infection 2 Year Infection Readmissions

Pe

rce

nta

ge

Subjects >65 with Axis I Disorders(N=3)Subjects >65 with No PsychiatricDisorders (N=6)

*p values insignificant

UCLA Experience: Axis II Pathology

Subjects with Axis II Disorders vs Subjects with No Psychiatric Disorders*

0

67

33

67

0

3

24

29

44

20

0

10

20

30

40

50

60

70

80

Mortality 1 Year Rejection 1 Year Infection 2 Year Infection Readmissions

Pe

rce

nta

ge

Subjects with Axis II Disorders(N=3)

Subjects with No PsychiatricDisorders (N=24)

*p values insignificant

Psychiatric Evaluations of Heart Transplant Candidates: Predicting Post-Transplant Hospitalizations, Rejection Episodes, and Survival

Owen, Bonds, WellischPsychosomatics 2006: 47:213-222

Predicting Outcomes

• There is no consensus among clinicians about which candidates are acceptable or unacceptable

• While psychosocial risk factors are routinely used to determine candidacy, there is limited predictive validity of the methods used

Hypothesis

• Previously identified psychiatric risk factors (eg. Recent substance abuse, history of suicide attempt, having a personality disorder, low levels of social support, and poor past adherence to medical regimens) would be associated with a greater likelihood of post-transplant complications

Outcome Measures

• Re-hospitalization/Rejection• Infection• Death

Methods

• 108 OHT recipients followed for average of 970 days

• Transplanted between 1997 and 2000

• >18 years old• Followed by UCLA Heart Transplant

Team

Findings –Psychiatric Risk Factors

• 77.8 had evidence of current Axis I disorder at time of evaluation– 40.4% mood disorder– 30.8% depression-related dx– 14.4% anxiety-related dx– 6.7% sleep disorder– 27.8% ETOH dependence or abuse

• 5.6% actively dependent on ETOH

• 41.7% using psychotropic meds

Risk Assessment

• Good Candidates – 50%• High Risk- 11.1%

Predictors of Transplant Outcomes

• Increasing psychiatric risk classification was associated with a greater hazard of post-transplant mortality, but was not predictive of either post-transplant infection (p=0.10) or hospitalization (p=0.62)

• Past history of suicide attempt strongly associated with time to infection/rejection

Predictors of Death

• 5 variables were associated with survival– Current employment (increases)– Hx of drug or ETOH detox– Current depressive disorder– Hx of past suicide attempt– Hx of poor medical adherence

Predictors of High Risk Classification

• Poor adherence• Past psychiatric hospitalization• Mood disorder• Axis II disorder• Use of psychiatric medications• Hx of ETOH or drug detox• Hx of substance abuse• Lack of social support

Demographic Predictors of Risk

• Age (younger)• Marital status (single)• Gender (female)

Survival as a Function of Psych Risk

Neuropsychiatric Aspects of Immunosuppressive Agents

• Cyclosporine• Neoral (microemulsified

cyclosporine)• Tacrolimus (FK506)• Cellcept (Mycophenolat mofetil)• Corticosteroids

Cyclosporine

Dosage Forms: PO, IV, IMSerum Levels: 200-350ng/ml

(300-350ng/ml first 3 - 6 months)

Anxiety, delirium, hallucinations, seizures,tremor, paresthesias, hirsutism, cerebral blindness

May elevate Li levels by increasing absorption at the proximal tubules

Neoral (po Cyclosporine)

Dosage Forms: POSerum Levels: 200-350ng/ml (300-350ng/ml first 3-6 months)

For patients who are poor absorbers of cyclosporine-similar S/E profileBoth are nephrotoxic, neurotoxic, and hepatotoxic

Lithium, nefazadone, fluoxetine and fluvoxamine may elevate levelsSt. John’s wort may decrease levels.

Tacrolimus (FK 506)

Dosage Forms: PO, IVSerum Levels: 8-15ng/ml

Anxiety, delirium, insomnia, restlessness

Cellcept (mycohpenolat mofetil)

Dosage Forms: PO, IV

Anxiety, depression, somnolence, nausea, vomiting

Corticosteroids

Dosage Forms: PO, IV

Delirium, euphoria, depression, mania, insomnia, tremor, irritability, weight gain, memory impairment

Organ Donation

• Christopherson and Lunde – studied the families of heart donors.

• Found 4 motivational factors:– History of heart disease in the family– Sophisticated awareness of medical

needs (most donated other organs also)

– An expressed wish of the donor prior to death

– Attempt to give meaning to the loss of loved one

Issues in Living Related Donation

• Informed Consent• Psychological Assessment

– non-uniform• Motivation for Donation

– Altruistic (anonymous donation)– Familial or other Relationship– Coercion

• Financial • Rejection of donated organ

Future Challenges

• Expanding OHT to previously excluded patient populations (eg. elderly, mentally ill)

• Exploring the safety and efficacy of psychotropics in OHT patients

• Developing structured interventions that enhance compliance

• Xenotransplantation• Transplantation of the Human Face• Artificial Organs

fin