Cited by 1,383Medication Adherence and ComplianceSchizophrenia research and treatmentMental Health Treatment and Access

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Prevalence of and Risk Factors for Medication Nonadherence in Patients With Schizophrenia: A Comprehensive Review of Recent Literature

Lacro, Jonathan P., Dunn, Laura B., Dolder, Christian R., Leckband, Susan G., Jeste, Dilip V.·2002·The Journal of Clinical Psychiatry

DOI 10.4088/jcp.v63n1007

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Abstract

OBJECTIVE: Nonadherence to prescribed antipsychotic medications places patients with schizophrenia at a greatly increased risk of illness exacerbation and rehospitalization. Identification of risk factors for nonadherence is an initial step toward designing effective interventions. This article reviews recent literature on the prevalence of and risk factors for medication nonadherence in patients with schizophrenia. DATA SOURCES: We searched the MEDLINE/HealthSTAR and PsycINFO databases using combinations of the keywords risk factor(s), adherence, compliance, antipsychotic, neuroleptic, schizophrenia, and psychosis for articles published since 1980 that identified risk factors for medication nonadherence in schizophrenia patients. We included reports that (1) were published in English and (2) specifically examined risk factors for medication nonadherence. Thirty-nine articles met our selection criteria. DATA SYNTHESIS: Among the 10 reports that met a strict set of study inclusion criteria, we found a mean rate of nonadherence of 41.2%; the 5 reports that met a stricter set of inclusion criteria had a mean nonadherence rate of 49.5%. In the 39 articles reviewed, factors most consistently associated with nonadherence included poor insight, negative attitude or subjective response toward medication, previous nonadherence, substance abuse, shorter illness duration, inadequate discharge planning or aftercare environment, and poorer therapeutic alliance. Findings regarding an association between adherence and medication type were inconclusive, although few studies explored this relationship. Other factors such as age, gender, ethnicity, marital status, education level, neurocognitive impairment, severity of psychotic symptoms, severity of medication side effects, higher antipsychotic dose, presence of mood symptoms, route of medication administration, and family involvement were not found to be consistent predictors of nonadherence. Limitations of the published literature are discussed. CONCLUSION: Efforts to improve medication adherence in patients with schizophrenia should target relevant risk factors.

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Background
Relationships among medication adherence, insight, and neurocognition in chronic schizophrenia
Na, E., Yim, S. J., Lee, J.-N., Kim, J. M., Hong, K., Hong, M., & Han, H. (2015) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12272 · Cited by 32
Wireless, noninvasive therapeutic drug monitoring system for saliva measurement toward medication management of schizophrenia
Yan, Z., Shi, Z., Wu, Y., Lv, J., Deng, P., Liu, G., An, Z., Che, Z., Lu, Y., Shan, J., et al. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115363 · Cited by 31
Twelve months of electronic monitoring (MEMS®) in the Swedish COAST-study: A comparison of methods for the measurement of adherence in schizophrenia
Brain, C., Sameby, B., Allerby, K., Lindström, E., Eberhard, J., Burns, T., & Wærn, M. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.11.013 · Cited by 31
“The magnitude of non-adherence varies widely between studies depending on cohorts studied, definitions of adherence and methods employed to rate adherence (Cooper et al., 2007; Lacro et al., 2002).”
Background
Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties
Montgomery, B., Treuer, Karagianis, Ascher‐Svanum, H., & Harrison (2012) · Patient Preference and Adherence · doi:10.2147/ppa.s27344 · Cited by 31
“1,11,12 Moreover, given the patient population, which often includes persons with limited insight into their illness, any measures that may help enhance palatability or acceptance of medication is likely to aid treatment adherence and persistence and improve long-term outcomes for the patient.”
Medication adherence of psychiatric patients in an outpatient setting
Mahaye, S. (2012) · African Journal of Pharmacy and Pharmacology · doi:10.5897/ajpp11.646 · Cited by 31
“Patients with schizophrenia, non-adherence rates range from 20 to 89% with an average rate of 50% (Lacro et al., 2002).”
Background
Agreement Between Patients With Schizophrenia and Providers on Factors of Antipsychotic Medication Adherence
Pyne, J. M., McSweeney, J. C., Kane, H. S., Harvey, S., Bragg, L., & Fischer, E. P. (2006) · Psychiatric Services · doi:10.1176/ps.2006.57.8.1170 · Cited by 31
Factors associated with antipsychotic medication adherence in community‐based patients with schizophrenia in Hong Kong: A cross sectional study
Bressington, D. T., Mui, J. H. C., & Gray, R. J. (2012) · International Journal of Mental Health Nursing · doi:10.1111/j.1447-0349.2012.00830.x · Cited by 31
“The importance of the relationship between insight and medication adherence in people with schizophrenia is highlighted by previous studies (i.e. Day et al. 2005; Lacro et al. 2002; Trauer & Sacks 2000).”
BackgroundResultInfluential
Impact of switching to long-acting injectable antipsychotics on health services use in the treatment of schizophrenia.
Lachaîne, J., Lapierre, M.-È., Abdalla, N., Rouleau, A., & Stip, É. (2015) · Europe PMC (PubMed Central) · Cited by 31
Medication adherence: predictive factors and enhancement strategies
Patel, M. X., & David, A. S. (2007) · Psychiatry · doi:10.1016/j.mppsy.2007.06.003 · Cited by 31
Using Pharmacy Data on Partial Adherence to Inform Clinical Care of Patients With Serious Mental Illness
Woltmann, E. M., Valenstein, M. M., Welsh, D. E., Lee, T. A., Wolschon, P. A., Grabowski, J. G., & Reilly, P. A. (2007) · Psychiatric Services · doi:10.1176/ps.2007.58.6.864 · Cited by 31
Financial incentives for patients in the treatment of psychosis
SZMUKLER, G. I. (2009) · Journal of Medical Ethics · doi:10.1136/jme.2008.027151 · Cited by 31
An exploratory, open-label, randomized trial comparing risperidone long-acting injectable with oral antipsychotic medication in the treatment of early psychosis.
Malla, A., Chue, P., Jordan, G., Stip, E., Koczerginski, D., Milliken, H., Joseph, A., Williams, R., Adams, B., Manchanda, R., et al. (2016) · Clinical Schizophrenia & Related Psychoses · doi:10.3371/csrp.mach.061213 · Cited by 30
Mental Health Nurses’ Tacit Knowledge of Strategies for Improving Medication Adherence for Schizophrenia: A Qualitative Study
Lin, Y.-Y., Yen, W.-J., Hou, W.-L., Liao, W.-C., & Lin, M.-L. (2022) · Healthcare · doi:10.3390/healthcare10030492 · Cited by 32
The Effect of Group Psychoeducation Program on Medication Adherence in Patients with Bipolar Mood Disorders: a Randomized Controlled Trial
Rahmani, F., Ebrahimi, H., Ranjbar, F., Razavi, S. S., & Asghari, E. (2016) · Journal of Caring Sciences · doi:10.15171/jcs.2016.030 · Cited by 30
Do financial incentives increase treatment adherence in people with severe mental illness? A systematic review
Burton, A., Marougka, S., & Priebe, S. (2010) · Epidemiologia e Psichiatria Sociale · doi:10.1017/s1121189x00001160 · Cited by 30
“Non-adherence to medication and treatment programmes by people with mental health problems is particularly common (Fenton et al., 1997; Lacro et al., 2002; Nosé et al., 2003) and is associated with a range of negative outcomes.”
Background
A pharmaco-economic analysis of patients with schizophrenia switching to generic risperidone involving a possible compliance loss
Treur, M., Heeg, B. M. S., Möller, H., Schmeding, A., & van Hout, B. (2009) · BMC Health Services Research · doi:10.1186/1472-6963-9-32 · Cited by 30
“Reported non-compliance rates for patients suffering from schizophrenia are relatively high, ranging from 40% to 50% [1-5] Non-compliance has been found to significantly increase the likelihood of hospitalization, inpatient charges, switching or augmenting therapy and symptoms.”
How do socio-demographic and clinical factors interact with adherence attitude profiles in schizophrenia? A cluster-analytical approach
Beck, E., Cavelti, M., Wirtz, M. A., Kossowsky, J., & Vauth, R. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2010.10.012 · Cited by 30
“Subjective factors found to affect adherence attitude for antipsychotics include subjective responses towards medication (Lacro et al., 2002), perceived daily benefits of medication (Fenton et al.”
Background
Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study
Schöttle, D., Janetzky, W., Luedecke, D., Beck, E., Correll, C. U., & Wiedemann, K. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1946-x · Cited by 29
Medication Adherence Using Electronic Monitoring in Severe Psychiatric Illness: 4 and 24 Weeks after Discharge
Lee, Y., Lee, M., Jeong, H., Youn, H., & Kim, S. (2019) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2019.17.2.288 · Cited by 30
Identifying Modifiable Risk Factors for Relapse in Patients With Schizophrenia in China
Mi, W., Chen, X.-M., Fan, T., Tabarak, S., Xiao, J., Cao, Y., Li, X., Bao, Y., Han, Y., Li, L., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.574763 · Cited by 30
The Potential Role of Long-Acting Injectable Antipsychotics in People With Schizophrenia and Comorbid Substance Use
Koola, M. M., Wehring, H. J., & Kelly, D. L. (2012) · Journal of Dual Diagnosis · doi:10.1080/15504263.2012.647345 · Cited by 30
“People with comorbid substance use are at an increased risk of nonadherence compared to those who do not use alcohol and illicit drugs (Drake et al., 1989; Owen et al., 1996; Swofford et al., 1996; Fenton et al., 1997; Olfson et al., 2000; Soyka, 2000a; Soyka, 2000b; Lacro et al., 2002; Margolese et al., 2004).”
Background
Stigma as a predictor of insight in schizophrenia
Pruß, L., Wiedl, K. H., & Waldorf, M. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2011.12.012 · Cited by 30
A randomized controlled trial with a Canadian electronic pill dispenser used to measure and improve medication adherence in patients with schizophrenia
Stip, É., Vincent, P. D., Sablier, J., Guevremont, C., Zhornitsky, S., & Tranulis, C. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00100 · Cited by 30
“The device provided estimates of implementation in FEP patients from the proportion of doses taken on time, which were in accordance with those found in the literature (Diaz et al., 2001; Lacro et al., 2002; Byerly et al., 2005; Remington, 2008; Lee et al., 2011).”
MethodResultInfluential
Relationship Between Diabetes and Mortality Among Persons With Co-occurring Psychotic and Substance Use Disorders
Jackson, C. T., Covell, N. H., Drake, R. E., & Essock, S. M. (2007) · Psychiatric Services · doi:10.1176/ps.2007.58.2.270 · Cited by 30
Telemedicine as a Tool to Improve Medicine Adherence in Patients with Affective Disorders – A Systematic Literature Review
Leiz, M., Pfeuffer, N., Rehner, L., Stentzel, U., & van den Berg, N. (2022) · Patient Preference and Adherence · doi:10.2147/ppa.s388106 · Cited by 29
“While there are many psychotropic drugs available today that can help to cure mental disorders, non-adherence is a major issue for sufficient treatment of mental disorders.(4,5) Non-adherence is associated with a number of negative consequences including relapse and worsening of symptoms, increased risk of rehospitali…”
Background
Personal and social functioning in schizophrenia: defining a clinically meaningful measure of maintenance in relapse prevention
Nicholl, D., Nasrallah, H. A., Nuamah, I. F., Akhras, K. S., Gagnon, D. D., & Gopal, S. (2010) · Current Medical Research and Opinion · doi:10.1185/03007991003798927 · Cited by 29
Health Care Resource Utilization and Costs Associated with Transitioning to 3-month Paliperidone Palmitate Among US Veterans
DerSarkissian, M., Lefèbvre, P., Joshi, K., Brown, B., Lafeuille, M., Bhak, R. H., Hellstern, M., Bobbili, P. J., Shiner, B. R., Khoury, A. C. E., et al. (2018) · Clinical Therapeutics · doi:10.1016/j.clinthera.2018.07.011 · Cited by 29
Check the effects: systematic assessment of antipsychotic side-effects in an inpatient cohort
Hynes-Ryan, C., McWilliams, S., Clarke, M., Fitzgerald, I., Feeney, L., Taylor, M., Boland, F., & Keating, D. (2020) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125320957119 · Cited by 29
Daily functioning and symptom factors contributing to attitudes toward antipsychotic treatment and treatment adherence in outpatients with schizophrenia spectrum disorders
Leijala, J., Kampman, O., Suvisaari, J., & Eskelinen, S. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03037-0 · Cited by 35
“Factors such as poor insight [13–18], substance abuse [14, 17, 19, 20], negative attitudes toward medication [9, 13, 17, 21, 22] and side-effects [19, 23] have been associated with non-adherence.”
Background
Association between previous and future antipsychotic adherence in patients initiating clozapine: real-world observational study
Brodeur, S., Courteau, J., Vanasse, A., Courteau, M., Stip, É., Fleury, M., LESAGE, A. D., Demers, M., Corbeil, O., Béchard, L., et al. (2022) · The British Journal of Psychiatry · doi:10.1192/bjp.2022.1 · Cited by 29
Update on the Etiology and Treatment of Schizophrenia and Bipolar Disorder
Buckley, P. F. (2008) · CNS Spectrums · doi:10.1017/s1092852900028212 · Cited by 29
La SUMD (Scale to Assess Unawareness of Mental Disorder): Validation et adaptation française dans une population de patients souffrant de schizophrénie
Raffard, S., Trouillet, R., Capdevielle, D., Gély-Nargeot, M.-C., Bayard, S., Larøi, F., & Boulenger, J. (2010) · The Canadian Journal of Psychiatry · doi:10.1177/070674371005500807 · Cited by 29
Therapeutic Drug Monitoring for Drugs Used in the Treatment of Substance-Related Disorders: Literature Review Using a Therapeutic Drug Monitoring Appropriateness Rating Scale
Brünen, S., Vincent, P. D., Baumann, P., Hiemke, C., & Havemann‐Reinecke, U. (2011) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e31822fbf7c · Cited by 29
“Patients treated with naltrexone and bupropion have a high rate of noncompliance, a property shared with clozapine, lithium, and nortryptiline.(36,70,117,121,122) In general, compliance is high in patients participating in opioid maintenance treatments, so we did not give points to buprenorphine and methadone for this…”
Background
The Effect of Race-Ethnicity on the Comparative Effectiveness of Clozapine Among Medicaid Beneficiaries
Horvitz-Lennon, M. V., Donohue, J. M., Lave, J. R., Alegria, M. M., & Normand, S. T. (2012) · Psychiatric Services · doi:10.1176/appi.ps.201200041 · Cited by 29
“Finally, some adherence studies (29–32) but not all (33) have found that blacks and Latinos are more likely to exhibit poor adherence to antipsychotics.”
Refill rate of antipsychotic drugs: an easy and inexpensive method to monitor patients' compliance by using computerised pharmacy data
Rijcken, C. A. W., Tobi, H., Vergouwen, A. C. M., & den Berg, L. T. W. D. J. (2004) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.951 · Cited by 29
“published a review of the current literature about risk factors for medication noncompliance in patients with schizophrenia.(10) The included studies showed a considerable heterogeneity of methods to evaluate compliance with a wide variation of criteria and cut-off levels.”
Background
Structure of needs among persons with schizophrenia
Korkeila, J. A., Heikkil�, J., Hansson, L. I., S�rgaard, K. W., Vahlberg, T. J., & Karlsson, H. (2005) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-005-0888-z · Cited by 29
“In addition, the abuse impedes the treatment adherence of patients with schizophrenia [19].”
Background
Effectiveness of long-acting injectable antipsychotics: a clinical perspective
Castillo, E. G., & Stroup, T. S. (2015) · Evidence Based Mental Health · doi:10.1136/eb-2015-102086 · Cited by 28
“A meta-analysis of studies that used trained personnel to measure antipsychotic medication adherence found that not ‘regularly taking medications as prescribed’ is prevalent in an average of 41% of participants across 10 studies.(3) Despite this high prevalence, providers are often unaware of this issue and generally…”
Background
Shame and Guilt in First-Episode Schizophrenia and Schizoaffective Disorders
Miller, R., & Mason, S. E. (2005) · Journal of Contemporary Psychotherapy · doi:10.1007/s10879-005-2701-4 · Cited by 31
Long-Term Real-World Effectiveness of Pharmacotherapies for Schizoaffective Disorder
Lintunen, J., Taipale, H. T., Tanskanen, A. J., Mittendorfer‐Rutz, E., Tiihonen, J., & Lähteenvuo, M. (2021) · Schizophrenia Bulletin · doi:10.1093/schbul/sbab004 · Cited by 32
Combining depot antipsychotic with an assertive monitoring programme for treating first‐episode schizophrenia in a resource‐constrained setting
Chiliza, B., Ojagbemi, A., Esan, O., Asmal, L., Oosthuizen, P. P., Kidd, M., Gureje, O., & Emsley, R. A. (2014) · Early Intervention in Psychiatry · doi:10.1111/eip.12141 · Cited by 28
Neurocognitive Correlates of Therapeutic Alliance in Schizophrenia
Davis, L. W., & Lysaker, P. H. (2004) · The Journal of Nervous and Mental Disease · doi:10.1097/01.nmd.0000131919.60151.a7 · Cited by 28
“Mirroring the findings of studies with other populations, therapeutic alliance in schizophrenia has been linked with treatment adherence and outcome (Gehrs and Goering, 1994; Lacro et al., 2002; Svensson and Hansson, 1999).”
Background
Detecting Potential Adverse Reactions of Sulpiride in Schizophrenic Patients by Prescription Sequence Symmetry Analysis
Lai, E. C., Hsieh, C. Y., Yang, Y. H. K., & Lin, S. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089795 · Cited by 28
“Such troublesome AEs may decrease quality of life and lead to future noncompliance of patients [36].”
Background

Authors: Lacro, J. P., Dunn, L. B., Dolder, C. R., Leckband, S. G., & Jeste, D. V.
Affiliations: University of California San Diego (US)
VA San Diego Healthcare System (US)
ORCID: Lacro, Jonathan P.
Dunn, Laura B.
Leckband, Susan G.
Jeste, Dilip V.
Venue: The Journal of Clinical Psychiatry
Publisher: Physicians Postgraduate Press, Inc
Published: 2002-10-15
Volume: 63
Issue: 10
Pages: 892-909
ISSN: 0160-6689 (ISSN-L)
DOI: 10.4088/jcp.v63n1007
OpenAlex: W2070893229
Cited by: 1,383
References: 74
Citations by year: 2026: 42 · 2025: 29 · 2024: 43 · 2023: 55 · 2022: 59 · 2021: 58 · 2020: 63 · 2019: 52 · 2018: 56 · 2017: 65 · 2016: 80 · 2015: 74 · 2014: 57 · 2013: 103 · 2012: 97
FWCI: 18.98
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r29mh056938-04)
National Institute of Mental Health (MH49671, R01MH059101, MH-43693, MH56938, MH59101, P30MH049671, MH-19934, T32MH019934)
Topics: Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
Keywords: medication non-adherence, schizophrenia, antipsychotic drugs, risk factors, prevalence, lack of insight, substance abuse, therapeutic relationship, aftercare planning, hospital readmission
MeSH terms: Adult, Ambulatory Care, Factor Analysis, Statistical, Female, Hospitalization, Humans, Male, Probability, Research Design, Risk Factors, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Prevalence, Treatment Refusal

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Prevalence of and Risk Factors for Medication Nonadherence in Patients With Schizophrenia: A Comprehensive Review of Recent Literature

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