Ethnopsychopharmacology/Palliative Care

Educational Objectives

The goals of this program are to improve management of psychiatric disorders through recognition of the influences of ethnicity and culture on pharmacodynamics and treatment acceptance, and to improve delivery of and increase psy­chiatrists’ participation in palliative care. After hearing and assimilating this program, the clinician will be better able to:

1.   Explain the role of the cytochrome P₄₅₀ oxidase system in the metabolism of medications.

2.   Discuss how genetic polymorphisms related to racial differences affect the metabolism of medications.

3.   Recognize the disparity between illness experiences in the United States and end-of-life preferences.

4.   State the roles of hospice and palliative care in relieving suffering.

5.   Summarize the treatment of depression and delirium in the palliative care environment.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose. In his lecture, Dr. Irwin discussed the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. McLeod-Bryant was recorded at 2009 Update in Psychiatry: Common Challenges in Psychopharmacology, held May 29-30, 2009, in Charleston, SC, and sponsored by the Medical University of South Carolina Institute of Psychiatry. Dr. Irwin was recorded at West Coast Geriatric Psychiatry Conference, held February 25-28, 2009, in San Diego, CA, and sponsored by the University of California, San Diego, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Ethnopsychopharmacology

Stephen McLeod-Bryant, MD, Associate Professor, Department of Psychiatry and Behavioral Sciences, Medical Univer­sity of South Carolina, Charleston

Metabolism of medications: most psychiatric medications metabolized by cytochrome P₄₅₀ oxidation system in liver; positive effect of medications determined by genes at receptor site and how they react to medication (phar­macokinetic effects); different alleles determine individual responses, and some alleles may be more common in some ethnic groups; pharmacodynamic effects probably more powerful, but not much known about effects of race and ethnicity

Cytochrome P 2D6 (CYP2D6): enzyme that metabolizes many psychiatric medications; study found people of Af­rican and Asian descent more likely to be slow or intermediate metabolizers in 2D6, while whites and those of Hispanic origin more likely to be ultraslow or poor metabolizers; concluded that 5% to 7% of whites and His­panic individuals would “have a real problem” with medications metabolized by 2D6, while Asian and African descendants would have intermediate problem; another study found that in geriatric population, poor metaboliz­ers had higher concentration of nortriptyline in their systems than their non-poor-metabolizing counterparts, even at lower average dosages; speaker suggests that side effects could be better predicted and/or avoided if individ­ual’s 2D6 allele could be determined

CYP2C19: studies suggest that whites and those of Hispanic origin may be faster metabolizers than people of Afri­can and Asian descent

CYP1A2: in Australian trial, whites of Anglo-Saxon descent needed almost twice as much clozapine to achieve same blood levels as those with Asian ancestry; however, even on higher dosages, whites significantly more sat­isfied with clozapine than those of Asian descent

Caveats: above studies done with relatively few particpants; >1 isoenzyme involved with metabolism of any given medicine; environmental factors, such as nicotine and caffeine, also influence metabolism of medications

Screening for cytochrome P₄₅₀ alleles: speaker opines that in near future, screening may become mandatory; gene chips in use (eg, by Mayo Clinic) to detect DNA polymorphisms that cause variation in protein expression; screen­ing currently costly, generally available only at particular laboratories, and requires long wait for results

Pharmacodynamics: defined as study of medication effect at site of action; polymorphisms in 5-HT and catechol-O-methyltransferase (COMT) have been detected, indicating complex interactions between ethnicity and alleles

Considerations in ethnopsychopharmacology: black and Asian Americans  —  may respond more rapidly and to lower doses of antidepressants than those required by whites; may be more sensitive than whites to antipsychot­ics (data suggest Asian Americans more sensitive than black Americans); in Asian and black Americans, benzo­diazepines may be effective at lower dosages  than in whites

Caveat: “black or Asian is a big lumping term”; color of individual’s skin does not accurately reflect genetic makeup

Perceptions and reality: in Indiana study, 400 psychiatrists asked to make diagnoses based on vignettes of patients with schizophrenia presenting to emergency department; patients differed only in description of race or sex;  pa­tients correctly identified as having schizophrenia 65% of time when race and sex not identified; when patients described as “black male,” 78% of psychiatrists diagnosed paranoid schizophrenia, and when patients described as “white female,” 41% made diagnosis other than schizophrenia

Effects on treatment practice and acceptance of treatment: study of insurance data assessed how often primary care physicians treated depression, and likelihood that antidepressant medication would be prescribed, based on num­ber of prescriptions written; racial disparity found, with whites most likely to receive prescriptions for antide­pressants, blacks least likely, and Hispanics in between; over 5 yr of study, greatest increase in prescriptions seen among Hispanics; however, speaker points out that differences not entirely due to clinician’s racial bias in pre­scribing, but also to ethnic differences in accepting prescriptions; per 2003 study, blacks third as likely as whites to accept medication prescription, while Hispanics half as likely; Hispanics 3 times more likely to accept coun­seling

Barriers to minority acceptance of medication: cost of medication; cost of prescriber’s evaluation; literacy and edu­cational level (medication instructions usually given in written form); English not primary language; mistrust (providers do not trust patients to adhere to medication regimen; patients do not trust providers)

Cultural formulation: speaker recommends LEARN mnemonic; listen to patient’s perception of his or her problems (which may be based on cultural tradition rather than on scientific and medical facts); explain provider’s perception of patient’s problems (based on scientific and medical facts); acknowledge differences and similarities in percep­tion; recommend treatment (keeping patient’s cultural expectations in mind); negotiate treatment

Conclusions: prevention of side effects in people of color will benefit from growing knowledge of interaction be­tween genes, culture, and medication; most evidence supports lower starting dosages and more cautious titrations of antidepressants and antipsychotics in individuals of Asian and African descent; side effects can further be pre­vented through addressing barriers to medications

The Role of Psychiatry in Palliative Care

Scott A. Irwin, MD, PhD, Faculty, Center of Palliative Studies; Clinical Instructor, Department of Psychiatry, University of California, San Diego, School of Medicine; Director, Psychiatry Program, San Diego Hospice & Palliative Care, San Di­ego, CA

Introduction: what adds meaning, quality, and value to life? highly variable from person to person, but common an­swers from healthy people include children, grandchildren, choice, community, relationships, pets, God or reli­gion, work, travel, outdoors, love, health, eating, and sex; patients given poor prognosis respond similarly, with addition of autonomy, death with dignity, and minimal pain

Models of illness: in past, people died suddenly and unexpectedly, often due to accidents or infectious diseases; physicians and health care workers had limited role, other than being with patient and family and administer­ing opiates, if necessary

Modern model: since introduction of antibiotics, medicine has advanced rapidly, and dying can be prolonged, with predictable decline; modern hospice movement spawned by need to care for patients whose death will oc­cur in next few weeks to months; currently, some diseases cured, but most controlled, with resulting »20-yr in­crease in life expectancy and with >90% of population living with chronic illnesses; some chronic diseases (eg, congestive heart failure, chronic obstructive pulmonary disease) marked by slow decline with periodic crises and sudden death; others (eg, Alzheimer disease) characterized by slow decline and unpredictable death

Multiple domains of patient and family suffering: disease management; feelings of loss and grief; physical, psy­chologic, social, and spiritual concerns; management of end-of-life and death; cost; emotional impact; speaker opines that psychiatrists could be helpful in many domains of suffering by offering support to patients, families, caregivers, and other people involved with decedent

Illness experiences in United States: 1) acute care, multiple trips to emergency department, multiple hospitaliza­tions, stays in intensive care unit, and maximum medical effort expended to prolong life; 2) long-term care with increasing dependence, caregiver burnout, transfer to long-term care facility, then slowly dwindling away; 3) can­cer model, involving first-line treatment, second-line treatment, perhaps followed by experimental treatment and transfer to hospice care; 4) living life to fullest, having diseases treated and suffering relieved, and dying at home; 90% of Americans believe family responsible for providing care for loved ones; 90% wish to die at home

What do people actually get? 23% die at home; 77% die in institutions (two-thirds in hospitals, one-third in nursing homes)

Palliative care: hospice and palliative care dedicated to giving people what they want at end of life; palliative care now accepted as medical subspecialty; purposes of palliative care to relieve suffering, and improve effectiveness of disease-modifying therapy, and improve quality of living, dying, and bereavement; may be combined with therapies aimed at remitting or curing illness or may be focus of care

Speaker’s model: patient presents with acute illness, which over time becomes chronic illness and, eventually, ad­vanced illness (defined as expecting patient to live £6 mo); palliative care provides life closure, management of actual death, and help with bereavement; medical specialists often not comfortable dealing with issues such as pain control, nausea control, depression, fear, and anxiety

Specific causes of suffering for which expertise of behavioral therapy specialist might be beneficial: anxiety; be­reavement; caregiver stress; delirium; dementia; depression; insomnia; desire for hastened death

Depression: affects £42% of patients receiving palliative care and 58% of those with advanced cancer; in study, pal­liative care experts able to identify only 10% to 14%; often mistreated, undertreated, or untreated; somatic symp­toms often not helpful in making diagnosis; focus on cognitive and emotional symptoms of dysphoria, despair, sadness, anhedonia, worthlessness, helplessness, hopelessness, guilt, loss of self-esteem, and desire for hastened death

Consequences of depression: undermining of self-esteem; worsening of medical illness and quality of life; length­ening of inpatient stays; interference with preparations for death, including capacity to make decisions, under­standing of situation, interaction with caregivers, and ability to reach final goals

Treatment of depression: pharmacologic or psychotherapeutic; review goals of care; relieve suffering pharmacolog­ically (determining first whether patient wants medication) and nonpharmacologically; consult mental health specialist for assistance when necessary; evidence exists that, in end-of-life care, group therapy reduces stress and mood symptoms

Dignity therapy: targeted at psychosocial and existential stress; in trial, satisfaction rate 91%; patients experienced heightened sense of dignity, purpose, and meaning, had increased will to live, and had reduced depressive symp­toms and sense of suffering

Complementary therapies: guided imagery; muscle relaxation; hypnosis; meditation; massage; aromatherapy; bright-light exposure; counsel patients to avoid caffeine and alcohol; treat insomnia; advise patients to exercise, if possible

Pharmacologic options: >24 antidepressants (with 7 mechanisms of action) available; American Psychiatric Asso­ciation (APA) guidelines for moderate to severe depression recommend combination of psychotherapy and anti­depressants, giving antidepressants 6 to 8 wk to work, then adjusting dose and allowing another 6 to 8 wk; however, many patients in hospice will not survive that long, so speaker uses psychostimulants instead of antide­pressants; psychostimulants  —  effective in hours to days; side effects minimal; can be continued indefinitely if no intolerance occurs; may reduce sedation if patient on opioids; may provide some adjuvant analgesia; for inpa­tients, speaker starts with 2.5 to 5 mg of methylphenidate at 8 am and repeats dose at noon; doubles dose every day until benefit stops or side effects occur; in outpatients, increase dosage more slowly; contraindications in­clude glaucoma, seizure disorder, and structural heart defects

Delirium: hypoactive delirium often misdiagnosed or unrecognized; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV TR) definition of delirium 1) disturbed consciousness with reduced ability to focus, sustain, or shift attention; 2) change in cognition or development of perceptual disturbance not ac­counted for by dementia; 3) develops over short period of time and tends to fluctuate throughout day; 4) evidence exists of underlying medical cause; occurs in £56% of hospitalized elderly, 70% to 87% of those in intensive care unit, and 25% to 85% of those with advanced cancer or near end of life; consequences  —  increased 6-mo mortality; increased overall mortality; prolonged hospitalizations; increased cost; stress, discomfort, and reduced quality of life for patients, family members, and caregivers (including physicians and nurses); treatment  —  review goals of care; relieve suffering pharmacologically or nonpharmacologically; consult mental health professional, if neces­sary; no medications approved by Food and Drug Administration for delirium; no published double-blind, random­ized, placebo-controlled trials; no consensus among oncologists, geriatricians, psychiatrists, and palliative medicine specialists; APA practice guidelines recommend ensuring safety in environment, addressing behavioral situations, treating with first-generation antipsychotics, and avoiding benzodiazepines (benzodiazepines not first-line treatment; may increase confusion, disinhibition, and falls); delirium becomes irreversible at end of life; can switch to benzodiazepines at this point (good sedative, amnestic, and muscle-relaxant effects, and can prevent sei­zures); in dementia-related agitation, antipsychotics may not be first choice of treatment (b-blockers, gabapentin, trazadone, and other drugs suggested, but without good evidence of efficacy)

Suggested Reading

Bertilsson L: Metabolism of antidepressant and neuroleptic drugs by cytochrome p450s: clinical and interethnic aspects. Clin Phar­macol Ther 82:606, 2007; Breslau J et al: Lifetime risk and persistence of psychiatric disorders across ethnic groups in the United States. Psychol Med 35:317, 2005; Cooper LA et al: The acceptability of treatment for depression among African-American, His­panic, and white primary care patients. Med Care 41:479, 2003; Fang CK et al: Prevalence, detection and treatment of delirium in terminal cancer inpatients: a prospective survey. Jpn J Clin Oncol 38:56, 2008; Ferris FD et al: A model to guide patient and family care: based on nationally accepted principles and norms of practice. J Pain Symptom Manage 24:106, 2002; Gilmer TP et al: Adher­ence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psy­chiatry 161:692, 2004; Irwin SA, Ferris FD: The opportunity for psychiatry in palliative care. Can J Psychiatry 53:713, 2008; Irwin SA et al: Psychiatric issues in palliative care: recognition of depression in patients enrolled in hospice care. J Palliat Med 11:158, 2008; Lesser I et al: Depression outcomes of Spanish- and English-speaking Hispanic outpatients in STAR*D. Psychiatr Serv 59:1273, 2008; Lewis-Fernández R, Díaz N: The cultural formulation: a method for assessing cultural factors affecting the clinical encounter. Psychiatr Q 73:271, 2002; Lunney JR et al: Patterns of functional decline at the end of life. JAMA 289:2387, 2003; Mur­phy GM Jr et al: CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression. Neuropsychopharmacology 25:737, 2001; Opolka JL et al: Role of ethnicity in predicting antipsychotic medication adherence. Ann Pharmacother 37:625, 2003; Trask PC: Assessment of depression in cancer patients. J Natl Cancer Inst Monogr. 32:80, 2004.