To conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens.
We searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles.
Study Eligibility Criteria, Participants, and Interventions
We included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence.
Study Appraisal and Synthesis Methods
Data abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis.
The estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures.
The meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used.
This analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
DiMatteo MR. Variations in patients' adherence to medical recommendations: A quantitative review of 50 years of research. Med Care. 2004;42:200–209.
World Health Organization. Adherence to long-term therapies: Evidence for action. Geneva, Switzerland: World Health Organization; 2003.
National Council on Patient Information and Education. Variations in patients' adherence to medical recommendations: A quantitative review of 50 years of research. Bethesda, MD; 2007.
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–97.
DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medial treatment outcomes: A meta-analysis. Med Care. 2002;40:794–811.
Wu JR, Moser DK, Chung ML, Lennie TA. Objectively measured, but not self-reported, medication adherence independently predicts event-free survival in patients with heart failure. J Card Fail. 2008;14:203–10.
Hiligsmann M, Rabenda V, Bruyere O, Reginster JY. The clinical and economic burden of non-adherence with oral bisphosphonates in osteoporotic patients. Health Policy. 2010;96:170–7.
Hiligsmann M, Rabenda V, Gathon HJ, Ethgen O, Reginster JY. Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif Tissue Int. 2010;86:202–10.
Davis KL, Edin HM, Allen JK. Prevalence and cost of medication nonadherence in Parkinson's disease: Evidence from administrative claims data. Mov Disord. 2010;25:474–80.
Kane SV, Chao J, Mulani PM. Adherence to infliximab maintenance therapy and health care utilization and costs by Crohn's disease patients. Adv Ther. 2009;26:936–46.
Heisler M, Choi H, Rosen AB, et al. Hospitalizations and deaths among adults with cardiovascular disease who underuse medications because of cost: A longitudinal analysis. Med Care. 2010;48:87–94.
Pinsky BW, Takemoto SK, Lentine KL, Burroughs TE, Schnitzler MA, Salvalaggio PR. Transplant outcomes and economic costs associated with patient noncompliance to immunosuppression. Am J Transplant. 2009;9:2597–606.
Breitscheidel L, Stamenitis S, Dippel FW, Schoffski O. Economic impact of compliance to treatment with antidiabetes medication in type 2 diabetes mellitus: A review paper. J Med Econ. 2010;13:8-15.
McGinnis BD, Olson KL, Delate TM, Stolcpart RS. Statin adherence and mortality in patients enrolled in a secondary prevention program. Am J Manag Care. 2009;15:689–95.
Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA. 2007;297:177–86.
Ho PM, Magid DJ, Masoudi FA, McClure DL, Rumsfeld JS. Adherence to cardioprotective medications and mortality among patients with diabetes and ischemic heart disease. BMC Cardiovasc Disord. 2006;6:48.
Kripalani S, Yao X, Haynes RB. Interventions to enhance medication adherence in chronic medical conditions: A systematic review. Arch Intern Med. 2007;167:540–50.
Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008 CD000011.
DiMatteo MR, Haskard KB, Williams SL. Health beliefs, disease severity, and patient adherence: A meta-analysis. Med Care. 2007;45:521–8.
DiMatteo MR. The role of effective communication with children and their families in fostering adherence to pediatric regimens. Patient Educ Counsel Special Issue: Educating and Counseling Children about Physical Health. 2004;55:339–344.
Zolnierek KB, Dimatteo MR. Physician communication and patient adherence to treatment: A meta-analysis. Med Care. 2009;47:826–34.
Gatti ME, Jacobson KL, Gazmararian JA, Schmotzer B, Kripalani S. Relationships between beliefs about medications and adherence. Am J Health Syst Pharm. 2009;66:657–64.
Manning WG Jr, Wells KB. The effects of psychological distress and psychological well-being on use of medical services. Medical Care. 1992;30:541–53.
Piette JD, Richardson C, Valenstein M. Addressing the needs of patients with multiple chronic illnesses: The case of diabetes and depression. Am J Manag Care. 2004;10:152–62.
DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: Meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101–7.
Gonzalez JS, Peyrot M, McCarl LA, et al. Depression and diabetes treatment nonadherence: A meta-analysis. Diabetes Care. 2008;31:2398–403.
Rosenthal R. Meta-analytic procedures for social research. Applied social research methods series. London: Sage; 1984.
Garber MC, Nau DP, Erickson SR, Aikens JE, Lawrence JB. The concordance of self-report with other measures of medication adherence: A summary of the literature. Med Care. 2004;42:649–52.
Andrade SE, Kahler KH, Frech F, Chan KA. Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf. 2006;15:565–74. discussion 575-7.
McHorney CA. The adherence estimator: A brief, proximal screener for patient propensity to adhere to prescription medications for chronic disease. Curr Med Res Opin. 2009;25:215–38.
Janson SL, Earnest G, Wong KP, Blanc PD. Predictors of asthma medication nonadherence. Heart Lung. 2008;37:211–8.
Balkrishnan R. Predictors of medication adherence in the elderly. Clin Ther. 1998;20:764–71.
Senior V, Marteau TM, Weinman J. Genetic Risk Assessment for FHTSG. Self-reported adherence to cholesterol-lowering medication in patients with familial hypercholesterolaemia: The role of illness perceptions. Cardiovasc Drugs Ther. 2004;18:475–81.
Kleinman A. Culture and depression. N Engl J Med. 2004;351:951–3.
Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133:21–30.
Mannheimer S, Friedland G, Matts J, Child C, Chesney M. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis. 2002;34:1115–21.
Hedges LV, Olkin I. Statistical methods for meta-analysis. San Diego, CA: Academic Press; 1985:xxii–369.
Peterson RA, Brown SP. On the use of beta coefficients in meta-analysis. J Appl Psychol. 2005;90:175–181.
Friedman DS, Okeke CO, Jampel HD, et al. Risk factors for poor adherence to eyedrops in electronically monitored patients with glaucoma. Ophthalmology. 2009; 116:1097-105.
Ross SM. Simulation. 4th ed. Amsterdam: Elsevier Academic Press; 2006:xiii–298 s.
Pearson K. Mathematical contributions to the theory of evolution. Vii, viii. Proceedings of the Royal Society. 1900; LXVI:140-164, 241-244.
Rosenthal R, Rosnow RL, Rubin DB. Contrasts and effect sizes in behavioral research: A correlational approach. New York, NY US: Cambridge University Press; 2000.
Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med. 1995;14:395–411.
StataCorp. Stata statistical software. In: Release 10. College Station. TX: StataCorp LP; 2007.
Mosley-Williams A, Lumley MA, Gillis M, Leisen J, Guice D. Barriers to treatment adherence among African American and white women with systemic lupus erythematosus. Arthritis Rheum. 2002;47:630–8.
Kronish IM, Rieckmann N, Halm EA, et al. Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes. J Gen Intern Med. 2006;21:1178–83.
Morgado A, Smith M, Lecrubier Y, Widlocher D. Depressed subjects unwittingly overreport poor social adjustment which they reappraise when recovered. J Nerv Ment Dis. 1991;179:614–9.
Steiner JF, Gardner EM. Assessing medication adherence from pharmacy records. Pharmacoepidemiology and Drug Safety. 2006;15:575–7.
Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: Results from the national comorbidity survey replication (ncs-r). JAMA. 2003;289:3095–105.
Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: Results from the national epidemiologic survey on alcoholism and related conditions. Arch Gen Psychiatr. 2005;62:1097–106.
Alexopoulos GS. Depression in the elderly. Lancet. 2005;365:1961–70.
Katon WJ, Rutter C, Simon G, et al. The association of comorbid depression with mortality in patients with type 2 diabetes. Diabetes Care. 2005;28:2668–72.
Hoen PW, Whooley MA, Martens EJ, Na B, van Melle JP, de Jonge P. Differential associations between specific depressive symptoms and cardiovascular prognosis in patients with stable coronary heart disease. J Am Coll Cardiol. 2010;56:838–44.
Saini SD, Schoenfeld P, Kaulback K, Dubinsky MC. Effect of medication dosing frequency on adherence in chronic diseases. Am J Manag Care. 2009;15:e22–33.
Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296–310.
Goldman DP, Joyce GF, Zheng Y. Prescription drug cost sharing: Associations with medication and medical utilization and spending and health. JAMA. 2007;298:61–9.
Gellad WF, Grenard JL, McGlynn EA. A review of barriers to medication adherence. In: A framework for driving policy options. Santa Monica, CA: RAND Corp; 2009.
Chapman RH, Ferrufino CP, Kowal SL, Classi P, Roberts CS. The cost and effectiveness of adherence-improving interventions for antihypertensive and lipid-lowering drugs*. Int J Clin Pract. 2010;64:169–81.
McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to medication prescriptions: Scientific review. JAMA. 2002;288:2868–79.
Fogarty L, Roter D, Larson S, Burke J, Gillespie J, Levy R. Patient adherence to HIV medication regimens: A review of published and abstract reports. Patient Educ Couns. 2002;46:93–108.
Malta M, Magnanini MM, Strathdee SA, Bastos FI. Adherence to antiretroviral therapy among HIV-infected drug users: A meta-analysis. AIDS Behav. 2010;14:731–47.
Cruess DG, Localio AR, Platt AB, et al. Patient attitudinal and behavioral factors associated with warfarin non-adherence at outpatient anticoagulation clinics. Int J Behav Med. 2010; 17:33–42.
Apter AJ, Boston RC, George M, et al. Modifiable barriers to adherence to inhaled steroids among adults with asthma: It's not just black and white. J Allergy Clin Immunol. 2003;111:1219–26.
Smith A, Krishnan JA, Bilderback A, Riekert KA, Rand CS, Bartlett SJ. Depressive symptoms and adherence to asthma therapy after hospital discharge. Chest. 2006;130:1034–8.
Gehi A, Haas D, Pipkin S, Whooley MA. Depression and medication adherence in outpatients with coronary heart disease: Findings from the heart and soul study. Arch Intern Med. 2005;165:2508–13.
Carney RM, Freedland KE, Eisen SA, Rich MW, Skala JA, Jaffe AS. Adherence to a prophylactic medication regimen in patients with symptomatic versus asymptomatic ischemic heart disease. Behav Med. 1998;24:35–9.
Ziegelstein RC, Fauerbach JA, Stevens SS, Romanelli J, Richter DP, Bush DE. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med. 2000;160:1818–23.
Mann DM, Ponieman D, Leventhal H, Halm EA. Predictors of adherence to diabetes medications: The role of disease and medication beliefs. J Behav Med. 2009;32:278–84.
Gonzalez JS, Safren SA, Delahanty LM, et al. Symptoms of depression prospectively predict poorer self-care in patients with type 2 diabetes. Diabet Med. 2008;25:1102–7.
Chao J, Nau DP, Aikens JE, Taylor SD. The mediating role of health beliefs in the relationship between depressive symptoms and medication adherence in persons with diabetes. Res Social Adm Pharm. 2005;1:508–25.
Hill-Briggs F, Gary TL, Bone LR, Hill MN, Levine DM, Brancati FL. Medication adherence and diabetes control in urban african americans with type 2 diabetes. Health Psychol. 2005;24:349–57.
Kalsekar ID, Madhavan SS, Amonkar MM, et al. Depression in patients with type 2 diabetes: Impact on adherence to oral hypoglycemic agents. Ann Pharmacother. 2006;40:605–11.
Kilbourne AM, Reynolds CF 3rd, Good CB, Sereika SM, Justice AC, Fine MJ. How does depression influence diabetes medication adherence in older patients? Am J Geriatr Psychiatry. 2005;13:202–10.
Wu JR, Moser DK, Chung ML, Lennie TA. Predictors of medication adherence using a multidimensional adherence model in patients with heart failure. J Card Fail. 2008;14:603–14.
Cukor D, Rosenthal DS, Jindal RM, Brown CD, Kimmel PL. Depression is an important contributor to low medication adherence in hemodialyzed patients and transplant recipients. Kidney Int. 2009; 75:1223–9.
Schoenthaler A, Chaplin WF, Allegrante JP, et al. Provider communication effects medication adherence in hypertensive african americans. Patient Educ Couns. 2009;75:185–91.
Schoenthaler A, Ogedegbe G, Allegrante JP. Self-efficacy mediates the relationship between depressive symptoms and medication adherence among hypertensive african americans. Health Educ Behav. 2009;36:127–37.
Chapman RH, Benner JS, Petrilla AA, et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med. 2005;165:1147–52.
Kim EY, Han HR, Jeong S, et al. Does knowledge matter?: Intentional medication nonadherence among middle-aged korean americans with high blood pressure. J Cardiovasc Nurs. 2007;22:397–404.
Morris AB, Li J, Kroenke K, Bruner-England TE, Young JM, Murray MD. Factors associated with drug adherence and blood pressure control in patients with hypertension. Pharmacotherapy. 2006;26:483–92.
Wang PS, Bohn RL, Knight E, Glynn RJ, Mogun H, Avorn J. Noncompliance with antihypertensive medications: The impact of depressive symptoms and psychosocial factors. J Gen Intern Med. 2002;17:504–11.
Stilley CS, Sereika S, Muldoon MF, Ryan CM, Dunbar-Jacob J. Psychological and cognitive function: Predictors of adherence with cholesterol lowering treatment. Ann Behav Med. 2004;27:117–24.
Insel K, Morrow D, Brewer B, Figueredo A. Executive function, working memory, and medication adherence among older adults. J Gerontol B Psychol Sci Soc Sci. 2006;61:P102–P107.
Van Houtven CH, Voils CI, Oddone EZ, et al. Perceived discrimination and reported delay of pharmacy prescriptions and medical tests. J Gen Intern Med. 2005;20:578–83.
Davis DP, Jandrisevits MD, Iles S, Weber TR, Gallo LC. Demographic, socioeconomic, and psychological factors related to medication non-adherence among emergency department patients. J Emerg Med. Epub 2009 May 21.
Gazmararian JA, Kripalani S, Miller MJ, Echt KV, Ren J, Rask K. Factors associated with medication refill adherence in cardiovascular-related diseases: A focus on health literacy. J Gen Intern Med. 2006;21:1215–21.
This research was supported by the Agency for Healthcare Research and Quality (AHRQ: T32 HS00046-14), a VA HSR&D Career Development Award to Dr. Gellad (CDA 09-207), and by Mehlman Vogel Castagnetti.
Conflicts of Interest
About this article
Cite this article
Grenard, J.L., Munjas, B.A., Adams, J.L. et al. Depression and Medication Adherence in the Treatment of Chronic Diseases in the United States: A Meta-Analysis. J GEN INTERN MED 26, 1175–1182 (2011). https://doi.org/10.1007/s11606-011-1704-y
- chronic disease