Evidence-Based Reviews

Overcoming medication nonadherence in schizophrenia: Strategies that can reduce harm

Current Psychiatry. 2013 November;12(11):14-20

References

1. Sun SX, Liu GG, Christensen DB, et al. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin. 2007;23:2305-2312.

2. Lacro JP, Dunn LB, Dolder CR, et al. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63:892-909.

3. Fenton WS, Blyler CR, Heinssen RK. Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull. 1997;23(4):637-651.

4. Olfson M, Mechanic D, Hansell S, et al. Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatr Serv. 2000;51(2):216-222.

5. Herings RM, Erkens JA. Increased suicide attempt rate among patients interrupting use of atypical antipsychotics. Pharmacoepidemial Drug Saf. 2003;12(5):423-424.

6. Weiden PJ, Kozma C, Grogg A, et al. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv. 2004;55(8):886-891.

7. Velligan D, Weiden P, Sajatovic M, et al. Assessment of adherence problems in patients with serious and persistent mental illness. J Psychiatr Pract. 2010;16(1):34-45.

8. Freudenreich O, Cather C, Evins A, et al. Attitudes of schizophrenia outpatients toward psychiatric medications: relationship to clinical variables and insight. J Clin Psychiatry. 2004;65(10):1372-1376.

9. Perkins DO, Johnson JL, Hamer RM, et al. Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode. Schizophr Res. 2006;83(1):53-63.

10. Olivares JM, Alptekin K, Azorin JM, et al. Psychiatrists’ awareness of adherence to antipsychotic medication in patients with schizophrenia: results from a survey conducted across Europe, the Middle East, and Africa. Patient Prefer Adherence. 2013;7:121-132.

11. Novick D, Haro J, Suarez D, et al. Predictors and clinical consequences of nonadherence with antipsychotic medication in the outpatient treatment of schizophrenia. Psychiatry Res. 2010;176(2-3):109-113.

12. Hunt GE, Bergen J, Bashir M, et al. Medication compliance and comorbid substance abuse in schizophrenia: impact on community survival four years after a relapse. Schizophr Res. 2002;54(3):253-264.

13. McGinty EE, Webster DW, Barry CL. Effects of news media messages about mass shootings on attitudes toward persons with serious mental illness and public support for gun control policies. Am J Psychiatry. 2013;170(5):494-501.

14. DiBonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry. 2012;12:20.

15. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;1382(9896): 951-962.

16. Robinson DS. Antipsychotics: pharmacology and clinical decision making. Primary Psychiatry. 2007;14(10):23-25.

17. Robinson D, Correll CU, Kane JM, et al. Practical dosing strategies in the treatment of schizophrenia. CNS Spectr. 2010;15:4(suppl 6):1-16.

18. Magura S, Rosenblum A, Fong C. Factors associated with medication adherence among psychiatric outpatients at substance abuse risk. Open Addict J. 2011;4:58-64.

19. Baloush-Kleinman V, Levine SZ, Roe D, et al. Adherence to antipsychotic drug treatment in early-episode schizophrenia: a six-month naturalistic follow-up study. Schizophr Res. 2011;130(1-3):176-181.

20. Byerly M, Nakonezny P, Lescouflair E. Antipsychotic medication adherence in schizophrenia. Psychiatr Clin North Am. 2007;30:437-452.

21. Pfeiffer PN, Ganoczy D, Valenstein M. Dosing frequency and adherence to antipsychotic medications. Psychiatr Serv. 2008;59(10):1207-1210.

22. Farooq S, Nazar Z, Irfan M, et al. Schizophrenia medication adherence in a resource-poor setting: randomized controlled trial of supervised treatment in out-patients for schizophrenia (STOPS). Br J Psychiatry. 2011;199(6):467-472.

23. Emsley R, Oosthuizen P, Koen L, et al. Oral vs injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Clin Ther. 2008;30(12):2378-2386.

24. Gutierrez-Casares JR, Canãs F, Rodriguez-Morales A, et al. Adherence to treatment and therapeutic strategies in schizophrenic patients: the ADHERE study. CNS Spectr. 2010;15(5):327-337.

Simplify the regimen. Using medications with once-daily dosing, for example, can help improve adherence. Pfeiffer and co-workers²¹ found that patients whose medication regimens were changed from once daily to more than once daily experienced a decrease in medication adherence. Conversely, a decrease in dosing frequency was significantly associated with improved adherence. More than once-daily dosing was only weakly associated with poorer adherence among patients already on a stable regimen.

Discussing positive and negative aspects of past medication trials with a patient and inquiring if she prefers a specific medication can be an effective way to build the therapeutic relationship and help with adherence.

Direct patients to psychosocial interventions. These can be broadly classified as:

educational approaches
group therapy approaches
family interventions
cognitive treatments
combination approaches.

Psychoeducational approaches have limited effect on improving adherence when delivered to individual patients. However, 1 study showed that psychoeducation was effective at improving adherence when extended to include the patient’s family.²²

Motivational interviewing techniques, behavioral approaches, and family interventions are effective at increasing medication adherence. One study looked at the value of training a patient-identified informant to supervise and administer medication. This person, usually a family member or close support, was responsible for obtaining medication from the pharmacy, administering the medication, and recording adherence. After 1 year, 67% of patients who used an informant were adherent, compared with only 45% in the group that did not have informant support.²² Case managers, attendant care workers, home health nurses, and assertive community treatment (ACT) teams also can participate in this manner; it is important, therefore, for you to be aware of the resources available in your community and to understand your role as patient advocate.

Substance abuse is a strong risk factor for nonadherence among patients with schizophrenia,¹⁸ which makes it important to assess patients for substance use and encourage those who do abuse to seek treatment. Although 1 study showed no correlation between Alcoholics Anonymous (AA) attendance and medication adherence,¹² many AA and Narcotics Anonymous groups do not discuss psychiatric medications during group meetings. Magura and colleagues encouraged the use of “dual focus” groups that involve mental health professionals and addiction treatment specialists discussing mental health and substance abuse issues at the same setting.¹⁸

Prescribe long-acting injectable antipsychotics. Typically, long-acting injectable antipsychotics (LAIs) are reserved for patients who have a history of nonadherence. In a small study (N = 97) comparing LAI risperidone and oral risperidone or oral haloperidol, patients treated with an LAI had significantly fewer all-cause discontinuations (26.0%, compared with 70.2%) at 24 months.²³ The Adherence to Treatment and Therapeutic Strategies in Schizophrenic Patients study examined 1,848 patients with schizophrenia and reached similar findings regarding LAI antipsychotics.²⁴ (Note: Aripiprazole, fluphenazine, haloperidol, olanzapine, and paliperidone also are available in an LAI formulation.)

Bottom Line

Antipsychotic nonadherence in schizophrenia is a major problem for patients, families, and society. Being able to identify patients at risk for nonadherence, understanding the reasons for their nonadherence, and seeking practical solutions to the problem are all the responsibility of the treating physician. Psychoeducation, addressing substance abuse, modifying dosing, and using long-acting injectable antipsychotics may help improve adherence.

Related Resources

Velligan DI, Weiden PJ, Sajatovic M, et al; Expert Consensus Panel on Adherence Problems in Serious and Persistent Mental Illness. Assessment of adherence problems in patients with serious and persistent mental illness: recommendations from the Expert Consensus Guidelines. J Clin Psychiatry. 2009;70(suppl 4):1-46.
National Alliance on Mental Illness. www.nami.org.
Assertive Community Treatment (ACT) Organization. www.actassociation.org.

Drug Brand Names

Aripiprazole • Abilify Chlorpromazine • Thorazine Clozapine • Clozaril Fluphenazine • Permitil Haloperidol • Haldol Iloperidone • Fanapt Olanzapine • Zyprexa Paliperidone • Invega Perphenazine • Trilafon Quetiapine • Seroquel Risperidone • Risperdal Ziprasidone • Geodon

Disclosures

Dr. Macaluso has been the principal investigator for clinical trials for AbbVie, Eisai, Envivo, Janssen, Naurex, and Pfizer. All clinical trial and study contracts and payments were made through the Kansas University Medical Center Research Institute. Dr. McKnight reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.