Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies

Abstract

Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive therapeutic alliance and good communication between the clinician and patient. These elements remain essential for all patients, not least for the small minority where vulnerability and risk issue dictate that compulsory treatment is necessary to ensure adherence.

Keywords: adherence; antipsychotics; long-acting injections; nonadherence; relapse; risk factors; schizophrenia.

Figure 1

Efficacy of maintenance antipsychotic medication versus placebo in schizophrenia (65 trials, n=6,493). Notes: Data are n/N (%) unless otherwise stated. The random effects model by DerSimonian and Laird was used throughout, with weights calculated by the Mantel–Haenszel method. *Weighted by sample size of individual trials. ^†Because of space limitations, we did not use the display suggested by Altman. Reprinted from The Lancet, 379, Leucht S, Tardy M, Komossa K, et al, Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis, 2063–2071, Copyright © 2012, with permission from Elsevier. Abbreviations: AE, adverse event; MD, movement disorder; n, number of participants with an event; N, number of studies; CI, confidence interval; NNTB/NNTH, number needed to treat to benefit/harm; H, harm; B, benefit.

Figure 2

Consequences of nonadherence to antipsychotic medication. Note: This material was originally published in Antipsychotic long-acting injections (edited by P Haddad, T Lambert and J Lauriello) and has been reproduced by permission of Oxford University Press. http://ukcatalogue.oup.com/product/9780199586042.do. For permission to reuse this material, please visit http://www.oup.co.uk/academic/rights/permissions. Abbreviation: QoL, Quality of life.

Figure 3

Association between antipsychotic nonadherence and outcome in a 3-year prospective observational US study. Notes: Adherence based on patient-reported adherence and medication possession ratio (% days with prescription for any antipsychotic). Data adapted from Ascher-Svanum H, Faries DE, Zhu B, Ernst FR, Swartz MS, Swanson JW. Medication adherence and long-term functional outcomes in the treatment of schizophrenia in usual care. J Clin Psychiatry. 2006;67(3):453–460. Copyright © 2006, Physician’s Postgraduate Press, Inc. Abbreviation: Psych, psychiatric.

Figure 4

Factors associated with nonadherence.