Evidence-Based Reviews

Overcoming medication nonadherence in schizophrenia: Strategies that can reduce harm

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

Dosing strategies, direct inquiry, psychoeducation can improve outcomes

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.

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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.

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Medication nonadherence is a common problem when treating patients with schizophrenia that can worsen prognosis and lead to sub-optimal treatment outcomes. In this article, we discuss common reasons for nonadherence and describe evidence-based treatments intended to increase adherence and improve outcomes (Box).^1-6

Common reasons for nonadherence

The primary predictor of future nonadherence is a history of nonadherence. It is important to understand patients’ reasons for nonadherence so that practical and evidence-based solutions can be implemented into the treatment plans of individual patients.

The 2009 Expert Consensus Guidelines on Adherence Problems in Patients with Serious and Persistent Mental Illness divided variables related to nonadherence into 3 categories:

those that lie within the patient (intrinsic)
those that are related to the patient’s relationship with healthcare providers, family, or caregivers (extrinsic)
those that are related to the healthcare delivery system (extrinsic).⁷

Among intrinsic variables, studies have shown a correlation between nonadherence and education level, lower socioeconomic status, homelessness, and male sex.⁷ (The Expert Consensus Guidelines considered homelessness to be an intrinsic factor because it was used as a demographic variable in the studies.)

Cognitive and negative symptoms associated with schizophrenia are an intrinsic risk factor for nonadherence because patients might not remember when or how to take medication.⁷ In a study by Freudenreich and co-workers⁸ of 81 outpatients who had a diagnosis of schizophrenia, the presence of negative symptoms predicted a negative attitude toward psychotropic medications. Poor insight might be the result of cognitive dysfunction associated with schizophrenia, and often is due to a lack of awareness of the importance of taking medications.

Limited insight into the need for treatment can be problematic early in the course of the illness when it may be directly related to positive symptoms. Perkins and colleagues⁹ demonstrated that patients recovering from a first psychotic episode who had limited insight into their illness and lacked desire to seek treatment were less adherent with medication. In another study, 5% of psychiatrists surveyed thought that many of their patients with schizophrenia were nonadherent because those patients did not believe that medications were effective or useful.¹⁰

Comorbid substance abuse disorders can contribute to medication nonadherence. In an analysis of 6,731 patients with schizophrenia, Novick and co-workers reported that alcohol dependence and substance abuse in the previous month predicted medication nonadherence.¹¹ Hunt and colleagues demonstrated that, among 99 nonadherent patients with schizophrenia, time to first readmission was shorter for patients with comorbid substance abuse disorders compared with patients who had a diagnosis of schizophrenia only. Over the 4-year study period, the 28 patients who had a dual diagnosis (schizophrenia and substance abuse) accounted for 57% of all hospital readmissions.¹²

Several variables that affect medication adherence are related to the patient’s relationship with healthcare providers, family, caregivers, and the service delivery system.⁷ These include:

the perceived stigma of being given a diagnosis of a serious mental illness
adverse effects related to medications
poor social and family support
difficulty gaining access to mental health services.^7,10

Societal stigma associated with seeking treatment from a mental health professional may contribute to nonadherence in some patients. In 1 study,¹³ 36% of people surveyed would not want to work closely with a person who has a serious mental illness.

Adverse effects contribute significantly to nonadherence

Limited treatment options (which may be expensive) can make it difficult to manage the adverse effects of antipsychotics. In a cross-sectional survey of 876 patients, investigators reported that: 1) <50% of patients were adherent with medication, and 2) 80% experienced ≥1 side effect that was reported to be “somewhat bothersome” in self-ratings (Table 1).¹⁴ Extrapyramidal symptoms (EPS) and agitation were most strongly associated with nonadherence; weight gain, akathisia, and sexual dysfunction also were associated with nonadherence.¹⁴ This study did not distinguish adverse effects associated with first-generation antipsychotics (FGAs) from those associated with second-generation antipsychotics (SGAs), even though 71.7% of patients studied were taking an SGA.

A meta-analysis by Leucht and co-workers¹⁵ compared 15 antipsychotics (the FGAs haloperidol and chlorpromazine and 13 SGAs) for efficacy and tolerability in schizophrenia. Haloperidol had the highest rate of discontinuation for any

cause; chlorpromazine was eighth, compared with all other drugs. Haloperidol and chlorpromazine were first and third, respectively, in terms of causing EPS. Haloperidol was the least likely to cause weight gain; only olanzapine, clozapine, and iloperidone caused more weight gain than chlorpromazine. Haloperidol was eighth in terms of sedation; only clozapine was reportedly more sedating than chlorpromazine.¹⁵

Antipsychotic binding affinities to dopamine 2 (D2), serotonin 2A (5-HT2A), histamine (H1), and other receptors have an impact on a medication’s side-effect profile. Because of individual patient characteristics, you might be faced with choosing a medication that has a lower risk of EPS but a higher risk of weight gain and metabolic complications—or the inverse. Understanding binding affinities, side-effect profiles, and how to minimize or utilize adverse effects (ie, giving a drug that is approved to treat schizophrenia and is associated with weight gain to a patient with schizophrenia who has lost weight) may lead to greater adherence (Table 2¹⁶ and Table 3¹⁷).