Recognition and Management of Depression and Co-morbidities in the Hispanic Population Friday, April l8, 10:00 a.m. – 12:00 p.m. National Hispanic Medical.

Recognition and Management of Depression and Co-morbidities

in the Hispanic Population

Recognition and Management of Depression and Co-morbidities

in the Hispanic Population

Friday, April l8, 10:00 a.m. – 12:00 p.m. National Hispanic Medical Association

12th Annual Conference

Washington HiltonWashington, D.C.

Supported by educational grants from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Company, Eli Lilly

and Company, Forest Laboratories, and Wyeth Pharmaceuticals

Julio Licinio, MDProfessor and Chairman Department of Psychiatry

Center for PharmacogenomicsAssociate Dean, Project Development

Miller School of MedicineUniversity of Miami

Miami, [email protected]

Depressed and Hispanic: Diagnostic and Treatment

Dilemmas

DisclosuresDisclosures

Employee: University of MiamiGrant/Research Support: NIHConsultant: Eli Lilly

Employee: University of MiamiGrant/Research Support: NIHConsultant: Eli Lilly

Goals and Objectives

• We aim to discuss cultural factors impacting on the diagnosis and treatment of depression in Hispanics.

• We will show results of recent studies on cultural barriers to diagnosis and treatment.

• We will present emerging genetic data on prediction of antidepressant treatment response in Mexican Americans.

Hispanics

• Chronic stress, early loss, deprivation are risk factors for depression• Common in Hispanic immigrants• Are Hispanic immigrants at higher risk for mental illness?• How do Hispanics deal with mental illness from a cultural perspective?• How do Hispanics respond to medication?• What are the rates of diagnosis, effective treatments and adequate follow up in Hispanics?

• Largest minority group in the United States.• 1 in 12 Americans are Mexican-American.• Buying power of Mexican-Americans the same as that of all of Mexico.• Limited number of trials and studies on Hispanic Health

The Concept of “Hispanic”

• Is it a language issue? What about Portuguese, or Mayan, or Aztec?• A common heritage? Which heritage?• An ethnicity?• Races?• Anyone could be Hispanic, from a person of pure northern European descent, to

African, or Asian backgrounds. • The majority are of Iberic peninsula heritage with different admixtures of native

American and African backgrounds.• Iberic peninsula itself is highly heterogeneous: Melting pot of Celtic, Latin, Basque,

Muslim, Jewish, Viking, and Germanic backgrounds.• Native America is highly heterogeneous, multitudes of languages, cultures and

backgrounds that came in separate waves from Asia and evolved differently in different places.

• Africans taken to America came over hundreds of years from myriad locations with vastly different cultures and backgrounds.

• Bottomline: The admixtures of highly heterogeneous groups can only be highly heterogeneous itself - Yet there is something in common. What is it?

Challenges in Diagnosis andTreatment of Depression in Hispanics

• CULTURE

• STIGMA

• COMPLIANCE

• LIMITED DATA

Diagnosing Hispanics - Points to Consider

• Is there a language barrier?• Is there a cultural barrier?• How are the symptoms of anxiety expressed in this culture?

Physical?Emotional?

• How are the symptoms of depression expressed in this culture?Physical?Emotional?

• How are the symptoms of psychosis expressed in the culture?Are there culturally-congruent non-reality based experiences?How are those differentiated from psychiatric symptoms, particularly prodomal ones?

• Do people seek early diagnosis or “hide” the problem?• Guilt • Shame• Do you tell patients their diagnosis?• What about their families?

Example: “You (your son) has a major depression and is at a high risk for killing himself.”

Treating Hispanics - Points to Consider

• Do patients express psychological symptoms somatically?• Does the patient accept the diagnosis and the need for treatment?• Will the patient accept the type of treatment?• Can they afford the treatment?• Do they understand they need to take medication way after they feel better?• Do they understand they will deteriorate if they stop taking meds on their own?• Do you trust what the patient tells you?• Does the patient trust what you tell him/her?• Will the patient accept a drug with a potential deleterious effect regarding sexual

function?• Will the patient tell you about sexual side effects?• Will men tell you what can be culturally perceived as weakness - “women’s stuff”:

• Sadness• Crying spells

• • Inadequacy• • Guilt• • Decreased libido• • Suicidality

Trauma, Domestic and Sexual Violence: Documented Risk Factors for Depression

• Is it disclosed?• What about non-traditional: women abusing men?• Will intervention worsen what can be a very precarious and hard

immigrant life?• When do you try to help?• When do you involve the legal system?• When and why do you keep the legal system aside?• Are there children in the picture?• What do you when you “know” it is happening but they will all

deny it?• Is it appropriate to call Child Protective Services on a “hunch”?• If you dismantle a family structure, albeit problematic, what do

you offer to replace it?

The Stigma of Antidepressant Treatment in Hispanics

• Data generated from six focus groups of Latino outpatients receiving antidepressants (N=30).

• Perceptions of stigma - related to both the diagnosis of depression and use of antidepressant medication.

• Antidepressant use - seen as implying more severe illness, weakness or failure to cope with problems, and being under the effects of a drug.

• Reports of stigma - related to social consequences. • Stigma - prominent concern among Latinos receiving antidepressants• Stigma often affected adherence. • Culture - important role in the communication of stigma and its

associated complications.

• Interian A, Martinez IE, Guarnaccia PJ, Vega WA, Escobar JI. Psychiatr Serv. 2007;58:1591-4. • A qualitative analysis of the perception of stigma among Latinos receiving antidepressants.

Stigma for Seeking Mental Health Treatment in Latinas

• Study examined the extent to which stigma-related concerns about mental health care account for the underuse of mental health services among low-income immigrant and U.S.-born black and Latina women.

• Participants: 15,383 low-income women screened for depression in county entitlement services asked about barriers to care, stigma-related concerns, and whether they wanted or were getting mental health care.

• Compared with U.S.-born white women, immigrant African women (OR=.18, p<.001), immigrant Caribbean women, U.S.-born black women, and U.S.-born Latinas were less likely to want treatment.

• Conversely, compared with U.S.-born white women, immigrant Latinas were more likely to want treatment.

• Stigma related to antidepressant treatment - greater in US-born than immigrant Latinas.

• Nadeem E, Lange JM, Edge D, Fongwa M, Belin T, Miranda J. Psychiatr Serv. 2007;58:1547-1554. • Does stigma keep poor young immigrant and U.S.-born Black and Latina women from seeking mental health care?

Diagnostic and Treatment Rates for Depression in Hispanics

• Data from the National Ambulatory Medical Care Survey for the time-frames 1992-1997, and 2003-2004: Partitioned into four, 2-year time intervals for trend analysis among patients aged 20-79 years.

• From 1992-1993 to 2003-2004, annualized rate of visits documenting diagnosis of depression increased from 10.9 to 15.4 per 100 US population for whites, from 4.2 to 7.6 for blacks, and from 4.8 to 7.0 for Hispanics.

• A concomitant diagnosis of depression and antidepressant use increased from 6.5 to 11.4 per 100 for whites, from 2.6 to 5.2 for blacks, and from 3.0 to 5.6 for Hispanics.

• By 2003-2004, diagnostic and treatment rates were comparable among blacks and Hispanic, but were less than half the observed rates for whites.

• Sclar DA, Robison LM, Skaer TL. Int Clin Psychopharmacol. 2008 Mar;23(2):106-109.• Ethnicity/race and the diagnosis of depression and use of antidepressants by adults in the United States.

•

Diagnostic and Treatment Rates for Depression in Hispanics

• Systematic review the literature to determine whether racial disparities exist in the diagnosis and treatment of depression in the United States.

• PubMed search of population-based studies examining the diagnosis and/or treatment of depression; or data from prospective studies stratifying the rates of diagnosis and/or treatment of depression by race/ethnicity and ethnic comparisons between Caucasians, African Americans and/or Hispanics.

• Initial searches identified 2,396 articles. • 14 articles: eligible for inclusion. • Four included data on the diagnosis of depression in different ethnic groups• Results were not consistent. • Twelve included data on treatment variability in the treatment of depression.

• Overall lower rates of treatment for African Americans and Hispanics than for Caucasians.

• More research is needed focusing on ethnic variation in the diagnosis of depression.

• Simpson SM, Krishnan LL, Kunik ME, Ruiz P. Psychiatr Q. 2007;78:3-14.• Racial disparities in diagnosis and treatment of depression: a literature review.

Hispanic and Suicide

• Data are from the National Violent Death Reporting System (NVDRS), a state-based data integration system

• For 2004 data from 13 US states. • NVDRS integrates medical examiner, toxicology, death certificate, and

law enforcement data. • Comorbid substance abuse and mental health problems were more

likely among non-Hispanic whites and non-Hispanic blacks, while Hispanics were more likely to have a substance abuse problem without comorbid mental health problems.

• Hispanics were less likely to have been diagnosed with a mental illness or to have received treatment, although family reports of depression were comparable to non-Hispanic whites and other racial/ethnic groups.

• Karch DL, Barker L, Strine TW. Inj Prev. 2006 Dec;12 Suppl 2:ii22-ii27.• Race/ethnicity, substance abuse, and mental illness among suicide victims in 13 US states: 2004 data from the

National Violent Death Reporting System.

Hispanic Perception of Antidepressant Treatment Modalities

Depressed Hispanic patients' perceptions of primary care treatments and the specific benefits associated with them.

Semi-structured interviews with 121 depressed Hispanic patients . More than half of patients viewed physician consultation and medication as helpful. Almost all patients considered psychotherapy to be helpful. Supportive talk - the most commonly mentioned specific benefit of physician

consultation. The most common benefit of medication: anxiolytic, sedative effect. Energizing effects: less common. Most common benefits associated with psychotherapy: support, advice, and

catharsis. Patients currently taking medication for depression had a more favorable view of

pharmacological treatment. Differences by language of interview were noted. English speakers - twice as likely as Spanish speakers to believe that medication

would have tonic effects, making them more active, energetic, or able to concentrate (21% vs 10%).

• Karasz A, Watkins L. Ann Fam Med. 2006;4:527-33. • Conceptual models of treatment in depressed Hispanic patients.

•

STAR*D Outcomes for Hispanics

Sequenced Treatment Alternatives to Relieve Depression (STAR*D) compared rates of remission and response for blacks (n = 495), whites (n = 1853), and Hispanics (n = 327) with non-psychotic major depressive disorder treated with citalopram.

Outpatients treated in 23 psychiatric and 18 primary care centers. Participants received flexible doses of citalopram for up to 14 weeks, with dosage

adjustments based on clinical assessments. Goal: remission. Significant differences among groups on many baseline demographic, sociocultural,

and clinical variables. Blacks and Hispanics - more socially disadvantaged and more co-morbidity than

whites. Before adjusting for differences, blacks had lower remission rates than whites, with

Hispanics intermediate between the 2. After adjustments, remission rates for groups were not significantly

different on the 17-item HRSD, but lower for blacks compared with whites with the 16-item QIDS-SR.

• Lesser IM, Castro DB, Gaynes BN, et al. Med Care. 2007;45:1043-51.• Ethnicity/race and outcome in the treatment of depression: results from STAR*D.

•

Antidepressant Discontinuation in Latinos

• Despite growth in number of antidepressant medications, many patients discontinue medication

• Reasons such as nonresponse, side effects, stigma, and miscommunication. • Some analysts have suggested that Latinos may have higher antidepressant

discontinuation rates than other US residents. • This paper examines Latino antidepressant discontinuation, using data from a

national probability survey of Latinos in the USA. • In this sample, 8% of Latinos had taken an antidepressant in the preceding 12

months. • Among those users, 33.3% had discontinued taking antidepressants at the time of

interview, and half had done so without prior input from their physician. • Even controlling for clinical and other variables, patients who reported good or

excellent English proficiency were less likely to stop at all. • Patients were also less likely to stop if they were older, married, had public or

private insurance, or had made eight or more visits to a nonmedical therapist.

• Hodgkin D, Volpe-Vartanian J, Alegría M. J Behav Health Serv Res. 2007;34:329-42. • Discontinuation of antidepressant medication among Latinos in the USA.

Cuban-Americans - UM Focus Group

• “Cuban” is primary identification - even for US born.• “Different” immigrant group.• Limited to no identification with newly arrived.• Common cultural values: Family - honor - word• View of medical research: “guinea pig” - suspicion.• Older individual: complete mistrust / suspicion of medical

establishment.• Take meds as they think right.• Share meds among friends/family.• Self medication with Rx meds - highly common.• Cultural shift - YUCAs - much more accepting of American

medicine and medical establishment.• Mistrust of drug companies whose mission is selling drugs.

Therefore, addressing symptoms, not searching for cures.• Hope: “cure” - Fear: unexpected side effects: “Celebrex.”

Pharmacogenomics of Antidepressant Treatment in Mexican Americans

• Phenotype: antidepressant response

• Genotype

• Candidates Systems• Specific Candidates• Bioinformatics approach to SNP

identification along pathways

• Searching for New Targets• Expression data• Genome-wide scan

• Clinical Translation

• Ethical Implications

“The complexity of this field is best approached by rigorous explorations of known candidate systems in conjunction with the use of genomic tools to discover new targets for antidepressants and to predict clinical outcomes.”

M-L Wong & J Licinio: Nature Reviews Neuroscience 2001;2:343-351.

Pharmacogenomics of AntidepressantTreatment in Mexican Americans Study

Features of the studyCreation of a phenotype-genotype with:

• DNA samples from 500-600 patients.• Correctly assigned phenotype (both for disease and course of drug response).• Treatment with two widely used drugs: fluoxetine, the most widely SSRI and desipramine, a TCA (both off patent).• (1 week single-blind placebo lead in, 8 weeks of double-blind drug)• Prospective, standardized, weekly treatment responses (continuum rather than categorical), by the same team of research clinicians.• Genotyping - performed collaboratively with Sanger Institute, Cambridge, UK.

Sharma A, et al.

Suicidality scores during double-blind fluoxetine and desipramine treatment in Mexican-Americans.

J Clin Psychopharmacology 2007;27:99-101

Suicide & Antidepressant

Use

Thestress

neuroendocrineneuroimmune axis

• A 32% effect of the GCG haplotype of antidepressant response

Conclusions• Depression is an important health problem in Hispanics (as much as

in the overall population).• Hispanics are the largest minority group in the US.• Cultural factors impact on the treatment of depression in Hispanics.• Rates of dx and tx are lower in Hispanics than in whites (<50%).• STAR*D - After adjustments, remission rates for groups were not

significantly different on the 17-item HRSD.• English speakers more likely to see benefits of pharmacological

antidepressant treatment.• Genetic factors also underlie the predisposition to depression and

antidepressant treatment response in Mexican-Americans.• Findings from Mexican-Americans replicated in others (Chinese,

African-Americans); from replication to scientific discovery.

Research Team and CollaborationsResearch Team and Collaborations

Sanger Institute, U.K. Panos Deloukas, PhD

Pamela Whittaker. PhD Marcos Delgado, PhD

UCLA Rita Cantor, PhD

David Elashoff, PhD Robert Elashoff, PhD Fiona Whelan, MSc

Harvard University - Brigham & Women ’s Scott Weiss, MD Kelan Tantisira, MD Steve Lake, PhD

NIMH Intramural Program Phil Gold, MD University of Düsseldorf, Germany Stefan Bornstein, MD, PhD

University of University of MiamiMiamiJulio Licinio, MD

Ma-Li Wong, MDJoao Vicente Busnello, MDLuciana Ribeiro, MDKarin Esposito, MD,PhDSamuel McCann, MD