Non-adherence is a significant issue for people with schizophrenia, with up to 74% of patients discontinuing antipsychotic (AP) therapy within 18 months of treatment.¹ Consequences of reduced adherence include higher rates of hospitalization,² increased number of treatment episodes,³ and increased frequency of suicide attempts.³ As a result, being able to accurately assess and improve adherence is a key consideration for physicians treating people with schizophrenia.

At the American Psychiatric Association Annual Meeting in 2022,      Dr. Leslie Citrome (Clinical Professor of Psychiatry and Behavioral Sciences at New York Medical College and Adjunct Clinical Professor of Psychiatry at Icahn School of Medicine, New York) provided a comprehensive analysis of the issues surrounding adherence assessment, and the assumption that physicians and providers are able to accurately assess adherence in their patients. 

Overestimation of adherence in schizophrenia

Studies have shown consistently that adherence is overestimated by clinicians.^4–8 Often, poor adherence may be mistaken as treatment resistance.⁷ In a study of people with schizophrenia who had been clinically identified as being treatment-resistant, over one-third were found to have either undetectable or sub-therapeutic plasma levels of AP, suggesting poor adherence.⁷ 

Listen to Dr. Citrome discuss how poor adherence may be mistaken as treatment resistance:

In a report comparing physician assessments of adherence with actual plasma levels of AP, almost 20% of patients who had been assessed as adherent had undetectable levels.⁸ Conversely, 25% of those who had been assessed as non-adherent had therapeutic levels of AP of 100% or greater. ⁸

Listen to Dr. Citrome compare clinician assessment of adherence with plasma levels of AP:

Investigations that use medication event monitoring systems (MEMS), which monitor how often medication bottles are opened, also indicate adherence can be overestimated. In three separate studies, MEMS reported higher levels of non-adherence than assessments by prescribers or patients.^4–6

Listen to Dr. Citrome discuss studies using MEMS to assess adherence:

Risk factors for non-adherence

Risk factors for non-adherence vary depending on the individual and can change over time. They can be subdivided into distinct categories:

• Patient-related – such as poor insight, negative attitudes towards medication, history of non adherence, substance use disorders, and cognitive impairment⁹
• Treatment-related – including side effects and lack of efficacy/continuation of symptoms⁹
• Environment- or relationship-related – including lack of support for the patient from their family or social network, problems with therapeutic alliance, and practical problems associated with obtaining or taking medications such as financial concerns or transportation⁹
• Society-related – including stigma, which can be related to the patient's illness or to the side effects of the medication 

Listen to Dr. Citrome emphasize the importance of indentifying the factors for individual patients:

Methods of measuring adherence

A number of methods to measure adherence exist, each with their own advantages and drawbacks. Indirect methods include patient self-reporting, questionnaires, and measuring clinical response or adverse events. While these methods are simple, they may be less reliable than direct methods. Conversely, direct methods may be more difficult to assess, but provide more reliable information. Examples of direct methods include observing ingestion, measuring levels of drug present in blood or bodily fluid, using biomarker or hair analysis, or using an ingestible marker or other digital health feedback system.¹¹

Listen to Dr. Citrome discuss methods for measuring adherence:

Use of long-acting injectables to address adherence issues

Use of long-acting injectables (LAIs) may be beneficial for improving adherence. The use of LAIs may provide more assurance to HCPs that the patient is continuously receiving their medication. Studies comparing LAIs with oral APs have found that the odds of achieving adherence are 1.4‐times higher with LAIs.¹² In fact, treatment guidelines recommend the use of LAIs if the patient has a history of poor or uncertain adherence.¹³ Therefore, the use of LAIs may provide more assurance to HCPs that the patient is indeed continuously receiving their medication – HCPs are aware when patients miss their appointment to receive their LAI, making monitoring and addressing non-adherence easier.¹⁴ Use of LAIs may also be useful in ruling out pseudo-resistance. The Treatment Response and Resistance in Psychosis (TRRIP) guidelines recommend that the definition of treatment resistance includes at least one failed trial with an LAI, given for at least 6 weeks after it has achieved steady state.¹⁵

In summary, it is a myth that physicians and providers know when patients are not adhering to their medication, and you can understand why this is by viewing the full presentations at APA 2022 here
To download Dr. Citrome’s presentation slides visit: https://uscnsb.tevapharm.com/scope-engage/

References

1. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209–23.
2. Ascher-Svanum H, Zhu B, Faries DE, et al. Medication adherence levels and differential use of mental-health services in the treatment of schizophrenia. BMC Res Notes 2009;2:6.
3. Ahn J, McCombs JS, Jung C, et al. Classifying patients by antipsychotic adherence patterns using latent class analysis: characteristics of nonadherent groups in the California Medicaid (Medi-Cal) Program. Value Health 2008;11:48–56.
4. Acosta FJ, Bosch E, Sarmiento G, et al. Evaluation of noncompliance in schizophrenia patients using electronic monitoring (MEMS®) and its relationship to sociodemographic, clinical and psychopathological variables. Schizophr Res 2009;107:213–7. 
5. Byerly MJ, Fisher R, Whatley K, et al. A comparison of electronic monitoring vs. clinician rating of antipsychotic adherence in outpatients with schizophrenia. Psychiatry Res 2005;133:129–33. 
6. Byerly MJ, Thompson A, Carmody T, et al. Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia. Psychiatr Serv 2007;58:844–7.  
7. McCutcheon R, Beck K, Bloomfield MAP, et al. Treatment resistant or resistant to treatment? Antipsychotic plasma levels in patients with poorly controlled psychotic symptoms. J Psychopharmacol 2015;29:892–7.
8. Lopez LV, Shaikh A, Merson J, et al. Accuracy of clinician assessments of medication status in the emergency setting: a comparison of clinician assessment of antipsychotic usage and plasma level determination. J Clin Psychopharmacol 2017;37:310–4.
9. Velligan DI, Weiden PJ, Sajatovic M, et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry 2009;70:1–46. 
10. Lee S, Chiu MYL, Tsang A, et al. Stigmatizing experience and structural discrimination associated with the treatment of schizophrenia in Hong Kong. Soc Sci Med 2006;62:1685–96.
11. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry 2013;12:216–26.
12. Lee S, Schwartz S. Adherence and persistence to long-acting injectable dopamine receptor blocking agent therapy in the United States: a systematic review and meta-analysis of cohort studies. Psychiatry Res 2021;306:114277
13. American Psychiatric Association. American Psychiatric Association practice guideline for the treatment of patients with schizophrenia, third edition. 2020. Available at: https://doi.org/10.1176/appi.books.9780890424841. Accessed October 2022.
14. Biagi E, Capuzzi E, Colmegna F, et al. Long-acting injectable antipsychotics in schizophrenia: literature review and practical perspective, with a focus on apriprazole once-monthly. Adv Ther 2017;34:1036–48
15. Howes OD, McCutcheon R, Agid O, et al. Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry 2017;174:216–29

Dr. Citrome’s full APA presentation: NPS-US-NP-01073

NPS-US-NP-01130