Appendix 2. Selected Articles on the Association Between Depression and Adherence to Medication
Appendix 2. Selected Articles on the Association between Depression and Adherence to Medication Therapies.
Citation / DiseaseStudied / Study
Design
& Dates / Number of Participants / Patients / Sample
Description / Measure of
Adherence / Measure of Depression / Bivariate Effect Size
(95% CI) / Multivariate Regression
Key Findings
Apter
et al.
2003[63] / Asthma / Observational
cohort
2000-2002 / Enrolled: 88
Responding
at f/u: 85 / Multiple clinic:
University of
Pennsylvania / Convenience
sample / Electronic monitoring: Prescribed doses
taken within
specified period / 20-item Center for Epidemiological Studies Depression Scale (CES-D), cutoff>=16 / -0.05
(-0.27, 0.16) / Depression was not significantly associated with adherence in bivariate analysis (OR = 0.99, 95% CI 0.95-1.03, P=.50). Thus, it was not included in the multivariate model.
Carney
et al.
1998[66] / Coronary
Heart
Disease / Observational
cohort
Dates not available / Enrolled: 78
Responding
at f/u: 62 / Single clinic/
hospital/
pharmacy / Convenience
sample / Electronic monitoring: Prescribed doses
taken within
specified period / Beck depression inventory / -0.24
(-0.50,0.01) / Multivariate analysis was not reported in this study.
Chao
et al.
2005[70] / Diabetes / Cross-
sectional
2003-2003 / Enrolled: 445 / Health plan:
Midwestern United States / Random
sample via mailings / Morisky and Horne scales / Patient Health Questionnaire (PHQ-8) / -0.24
(-0.34,
-0.15) / In structural equation modeling, no direct effect was found between depressive symptoms and adherence (Beta =
-0.04), althoughthe relationship
may be mediated through
perceived barriers to medication use, perceived side-effects, and
self-efficacy.
Chapman
et al.
2005[78] / Hyperlipidemia
Hypertension / Retrospective
cohort
1997-2001 / Enrolled: 8,406
/ Health plan / All new patients
with disease
from study site / Proportion
of days covered / Depression diagnosis in chart
/ -0.02
(-0.50, 0.45) / Depression diagnosis was not associated with adherence in a multivariate model (OR = 0.94; 95% CI 0.78,1.13; P=.51) after adjusting for demographics, comorbidity, and history of health services use.
Cruess
et al.
2009[62] / Anticoagulation
therapy / Prospective
cohort
Dates not available / Enrolled: 156
/ Multiple clinics: Pennsylvania / All patients
with disease
from study site / Electronic monitoring: Prescribed doses
taken with
specified period / Millon Behavioral Medicine Diagnostic depression subscale
/ -0.13
(-1.47, 1.20) / Depression was not significant in a logistic regression model (OR = .006; 95% CI -.018,0.03; P = .64) after adjusting for demographics, indication for warfarin, and clinic site.
Cukor
et al.
2009[75] / Kidney
transplant,
Hemodialysis / Cross-
sectional
Dates not available / Enrolled: 159
/ Single clinic/
hospital/
pharmacy:
New York / Convenience
sample / Medication Therapy
Adherence Scale / Beck Depression Inventory (BDI)
/ -0.51
(-0.67,
-0.35) / In a multiple regression model, depression was significantly associated with adherence (beta =
-.287, P<.01) after adjusting for demographics, mode of treatment, and locus of control.
Davis
et al.
2009[85] / Diabetes,
Hypertension,
Seizures / Cross-
sectional
Dates not available / Enrolled: 472
/ Single clinic/
hospital/
pharmacy / Convenience
sample / Self report, 2 items / Brief Symptom Index of Depression 7 items
/ -0.21
(-0.92, 0.49) / Depression was significantly associated with lower adherence in a multivariate model (OR = 2.83; 95% CI 1.63, 4.91; P < .001) after adjusting for demographics and drug/alcohol use.
Friedman
et al.
2009[39] / Glaucoma / Observational
cohort
2006-2007 / Enrolled: 282
Responding
at f/u: 196 / Multiple sites / All non-surgical patients
with disease
from study site / Travatan Dosing Aid: Prescribed doses
taken with
specified period,
Cutoff: 75% / 10-item Center for Epidemiological Studies Short Depression scale
/ -0.11
(-0.26, 0.03) / Depression was not significant in the multivariate model.
Gatti
et al.
2009[22] / Hypertension, Hyperlipidemia, Diabetes, Other / Cross-
sectional
June – Oct 2006 / Enrolled: 281
Responding
at f/u: 275 / Multiple pharmacies:
Atlanta,
Georgia / Systematic Convenience Sample / Morisky-8 Item Medication Adherence Scale / 1-question from 12-item Medical Outcomes Survey (MOS SF-12)
/ -0.18
(-1.07, 0.71) / Depressive symptoms were not associated with adherence in multivariate analysis adjusting for health literacy andbeliefs about medication.
Gazmararian
et al.
2006[86] / Coronary
Heart Disease
Diabetes
Hyperlipidemia
Hypertension / Observational
cohort
Dates not available / Enrolled: 1,540 / Multiple sites: Ohio, Texas, and Florida / All patients
with disease
from study site / Cumulative
medication gap based upon pharmacy claims, Cutoff: 80% / Self-report
/ 0.00
(-0.05, 0.05) / Depression was not associated with medication adherence in bivariate analysis and was not included in the multivariate model.
Gehi
et al.
2005[65] / Coronary
Heart
Disease / Cross-
sectional
2000-2002 / Enrolled: 940
/ Multiple sites in California / All patients
with disease
from study site / Self report using 3 questions / Patient Health Questionnaire (PHQ-9)
/ -0.13
(-0.76, 0.50) / Depression was associated with not taking medication as prescribed (OR = 2.2, 95% CI: 1.2, 3.9) after adjusting for demographics, medical history, medication use and cardiac function.
Gonzalez
et al.
2008[69] / Diabetes / Observational
cohort
2001-2003 / Enrolled: 208 / Two clinics in
Massachusetts / All patients
with disease
from study site / Self-Report of prescribed doses
taken in the past 7 days,
Cutoff: 100% / 10-item Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) / -0.19
(-0.32,
-0.05) / Depression was associated with non-adherence (OR=1.08; 95% CI 1.001, 1.16) after controlling for demographics, comorbidity, and baseline self-care.
Hill-Briggs
et al.
2005[71] / Diabetes / Cross-
sectional
1995-1997 / Enrolled: 172 / African Americans from multiple clinics: Johns
Hopkins, Maryland / Participants
in clinical trial / Modified Morisky / 20-item Center for Epidemiological Studies Depression Scale (CES-D) / -0.13
(-0.28, 0.02) / Multivariate analysis of
depression and adherence was not performed.
Insel
et al.
2006[83] / Hyperlipidemia,
Hypertension,
Arthritis / Observational
cohort
Dates not available / Enrolled: 100
/ Community
sample / Convenience
sample / Proportion
of days covered using medication monitoring caps. / 30-item Geriatric Depression Scale (GDS)
/ 0.02
(-0.18, 0.22) / Depression was not associated with medication adherence scores in multivariate regression after controlling for demographics, illness severity, and executive functioning.
Janson
et al.
2008[31] / Asthma / Observational cohort
2000-2003 / Enrolled: 113
/ Multiple
clinic:
Northern
California / Convenience
sample / Self-report prescribed doses
taken with
specified period,
Cutoff: 50% / 20-item Center for Epidemiological Studies Depression Scale (CES-D), cutoff>=16
/ -0.04
(-0.23, 0.14) / Depression was not associated with medication adherence in bivariate analysis and was not included in the multivariate model.
Kalsekar
et al.
2006[72] / Diabetes / Observational
cohort
1998-2001 / Invited: 1,326
/ State:
West Virginia Medicaid / All patients
with disease
from study site / Medication
possession
ratio / Depression diagnosis in chart
/ -0.10
(-0.16,
-0.05) / Depression was associated with non-adherence (beta=-0.057, P=0.019) after adjusting for demographics, comorbidity, provider interactions, treatment complexity, and diabetes severity.
Kilbourne
et al.
2005[73] / Diabetes / Observational
cohort
2000-2001 / Enrolled: 203
Responding
at f/u: 196
/ Single
clinic/
hospital/
pharmacy:
VA / All patients
with disease
from study site / Electronic medication monitoring 30 days and prescription refill data / Patient Health Questionnaire (PHQ-9)
/ -0.16
(-1.24, 0.91) / Depression was associated with 20% fewer days with adequate medication coverage based on pharmacy fill data (beta= -20, 95% CI -40, -1) after adjusting for demographics, cognitive impairment, binge drinking, and number of medications.
Kim
et al.
2007[79] / Hypertension / Cross-
sectional
2003-2004 / Enrolled: 208
/ Community sample from Baltimore-
Washington
area / Participants
in clinical trial / Modified Hill-Bone
Compliance Scale / 21-item Kim depression Scale for Korean Americans (KDSKA)
/ -0.30
(-0.44,
-0.17) / There was no significant relationship between depression and intentional (OR 1.012, 95% CI 0.95, 1.07) or non-intentional (OR 1.02, 95% CI 0.97, 1.07) non-adherence after adjusting for demographics, comorbid conditions, adverse effects, social support, satisfaction with care, and high blood pressure knowledge, beliefs and self-efficacy.
Kronish
et al.
2006[46] / Coronary
Heart
Disease / Observational
cohort
2003-2005 / Enrolled: 560
Responding
at f/u: 492 / Three sites in New Jersey, New York, and Connecticut. / All patients
with disease
from study site / Validated
scale:
Morisky / Beck Depression Inventory (BDI)
/ -0.23
(-1.16, 0.70) / Patients with persistent depression after 3 months were significantly less likely to report taking medications as prescribed (OR 0.50, 95% CI 0.27, 0.95) after adjusting for demographics and comorbidity.
Mann
et al.
2009[68] / Diabetes / Cross-
sectional
2007-2007 / Enrolled: 151
/ Single clinic/
hospital/
pharmacy:
New York City / Convenience
sample / Morisky scale / Patient Health Questionnaire (PHQ-9), cutoff ≥10
/ -0.18
(-1.39, 1.03) / Depression was non-significant and dropped from the multivariate model in stepwise elimination.
Morris
et al.
2006[80] / Hypertension / Cross-
sectional
2002-2003 / Enrolled: 492
/ Single clinic/
hospital/
pharmacy:
Indiana / Participants
in clinical trial / 1. Prescription Claims: Medication
possession
ratio
2. Morisky scale (modified) / Patient Health Questionnaire (PHQ-8), cutoff ≥10
/ -0.05
(-0.75, 0.66) / Depression was not significantly associated with refill adherence (OR 0.94, 95% CI 0.63, 1.40) after adjusting for age, marital status, and race. Depression was, however, associated with self-reported adherence (OR 0.48, 95% CI 0.32, 0.72).
Mosley-Williams
et al.
2002[45] / Systemic Lupus Erythematosus / Cross-
sectional
Dates not available / Enrolled: 68 / Multiple
clinics: African American women / Random
sample / Self Report: frequency of failing to take medications when prescribed during the past year (5-point Likert) / 20-item Center for Epidemiological Studies Depression Scale (CES-D) / -0.37
(-0.61,
-0.12) / Multivariate analysis of
depression and adherence was not performed.
Mosley-Williams
et al.
2002[45] / Systemic Lupus Erythematosus / Cross-
sectional
Dates not available / Enrolled: 54 / Multiple clinics: Caucasian Women / Random
sample / Self Report: frequency of failing to take medications when prescribed during the past year (5-point Likert) / 20-item Center for Epidemiological Studies Depression Scale (CES-D) / -0.06
(-0.36, 0.24) / Multivariate analysis of
depression and adherence was not performed.
Schoenthaler
Chaplin,
et al.
2009[76] / Hypertension / Cross-
sectional
Dates not available / Enrolled: 439
/ Multiple clinics:
New York City / All patients with disease from study site / Morisky scale / Patient Health Questionnaire (PHQ-9)
/ -0.23
(-0.33,
-0.14) / Depressive symptoms were significantly associated with lower medication adherence (β =
-.18, P=.001) after adjusting for age, gender, education, income, comorbidity, provider degree, and provider communication.
Schoenthaler
Ogedegbe,
et al.
2009[77] / Hypertension / Observational
cohort
Dates not available / Enrolled: 190
Responding
at FU: 167 / Multiple clinics:
New York City / All patients
with disease
from study site / Morisky scale / 20-item Center for Epidemiological Studies Depression Scale (CES-D), cutoff ≥16
/ -0.17
(-0.32,
-0.01) / Medication adherence at 3-month follow-up was not associated with baseline depressive symptoms (beta=0.010, P=.087 after adjusting for the mediating effects of self-efficacy.
Smith
et al.
2006[64] / Asthma / Observational
cohort
2001-2002 / Enrolled: 82
Responding
at f/u: 59 / Single clinic/
hospital/
pharmacy:
Baltimore / Consecutive
patients / Electronic monitoring: Prescribed doses
taken within 2-week period.
/ 11-item Center for Epidemiologic Studies-Depression (CES-D) scale, cutoff ≥10
/ -0.16
(-0.42, 0.10) / Depressive symptoms were significantly associated with adherence to asthma therapy (beta=-0.016, P=0.028) after controlling for age, gender, and education.
Stilley
et al.
2004[82] / Hyperlipidemia / Observational
cohort
1992-1995 / Enrolled: 158 / Community Sample:
Southwest Pennsylvania / Volunteers,
response to ads / Electronic monitoring: Percent days compliant / Hamilton Depression Scale / -0.24
(-0.40,
-0.08) / Depression was not examined as an independent predictor in multivariate analysis. Psychologic distress (anxiety or depression) was not associated in fully adjusted models with adherence that controlled for personality, intelligence, mental flexibility and verbal learning.
Van Houtven
et al.
2005[84] / Not specified / Cross-
sectional
2002 / Enrolled: 545 / Community Sample:
DurhamCounty / Random
sample / Self Report: “During the past 12 months, did you either delay or not get a prescription that a doctor or provider prescribed for you?” / PRIME-MD 1000 Depression Measure
/ -0.22
(-1.04, 0.60) / Feeling down or depressed was significantly associated with delaying or not getting a prescription (OR=2.71; 95%CI: 1.58, 4.66) after adjusting for demographics, economic constraints, self-reported health, and perceived discrimination.
Wang
et al.
2002[81] / Hypertension / Cross-
sectional
1996 / Enrolled: 496
/ Multiple clinics:
Boston / Random
sample / Prescription claims: Proportion
of days covered / Brief Symptom Inventory Depression Subscale
/ -0.04
(-0.13, 0.05) / Depressive symptom severity was associated with non-adherence (OR=0.93; 95%CI: 0.87, 0.99 for every point increase in the 14-point depression score) after adjusting for demographics, site of treatment, the use of thiazide diuretics, locus of control, and the presence of comorbid medical conditions.
Wu
et al.
2008[74] / Heart
failure / Observational
cohort
Dates not available / Enrolled: 134
/ Multiple clinics:
Kentucky / Convenience
sample / Electronic monitoring: Proportion of days correct number of doses taken. / Patient Health Questionnaire (PHQ-9)
/ -0.21
(-0.38,
-0.04) / Depression was not significantly associated with adherence measured as the percentage of correct doses taken per day (beta=0.028, P=0.790) after adjustment for demographics including SES, comorbidity, treatment variables, and relationship with provider.
Ziegelstein
et al.
2000[67] / Coronary
Heart
Disease post Myocardial Infarction / Observational
cohort
Dates not available / Enrolled: 276
Responding
at f/u: 204 / Single clinic/
hospital/
pharmacy:
Maryland / Consecutive
patients / Medical Outcomes Study Adherence Specific Scale / Beck Depression Inventory: cutoff ≥10 / -0.06
(-0.19,
-0.08) / Results for multivariate analyses were not provided.