Contributor: Patient-Centered Approaches to Supporting Medication Adherence Among Persons With Schizophrenia

Mental Health Awareness Month provides opportunities to offer information about one of the most challenging conditions for patients and families: schizophrenia.

Mental health matters | Image credit: netrun78 - stock.adobe.com

This article briefly describes schizophrenia, some of the challenges patients and families experience, especially with regard to medication adherence, and approaches the health care ecosystem can adopt to remove barriers and support access, adherence, and recovery.

Schizophrenia: 8 Key Facts

• Schizophrenia is a complex, long-term condition in which individuals may experience confused cognition, emotions, and behavior.
• It is estimated that persons with schizophrenia die 15‐20 years prematurely.¹
• Symptoms vary among individuals, commonly emerge in young adulthood, and typically fall into 3 categories:
  • Positive symptoms: e.g., hallucinations, delusions, and distorted perceptions
  • Negative symptoms: e.g., emotional “numbness,” social isolation, and diminished motivation
  • Cognitive symptoms: e.g., disorganized thinking, speech, reasoning, and behaviors
• Persons with schizophrenia comprise about 1% of the population, and the excess economic burden within the U.S. has been estimated at $343 billion.²
• Despite common misconceptions, schizophrenia does not entail a “split personality,” “multiple personalities,” or dissociative identity disorder.
• The causes of schizophrenia remain uncertain, but genetic predisposition, environmental triggers, biological factors, and brain structure are thought to play a role in the development of the condition.³
• Presently, there is no cure for this condition. The most common medications for the treatment of schizophrenia are atypical antipsychotics (also called “second generation” antipsychotics), which are preferred over “first generation” antipsychotics because of their more favorable efficacy, persistence, and adherence rates.⁴
• Reported non-adherence with medication varies greatly, with rates ranging from 4% to 72%, but the estimated mean rate is closer to 50%.^5,6

While atypical antipsychotics are associated with fewer adverse effects (AEs), patients sometimes report AEs such as restlessness, difficulty sleeping, and sexual dysfunction. Weight gain, increased risk of diabetes, high cholesterol, and kidney or bladder problems are also present.⁷ Therefore, patients on these medications should have their weight, glucose and lipid levels, and renal functions regularly checked.

Potential AEs, as well as other factors, create nonadherence challenges for patients, often leading to clinical, social, and economic repercussions.

Why Adherence Matters: The Impacts of Nonadherence

The efficacy of medications relies significantly on individuals' access to and adherence to medications. In the context of conditions like schizophrenia, where pharmacotherapy plays a pivotal role in symptom management, stabilization, and recovery, consistent medication use is paramount for achieving positive treatment outcomes. However, the reality persists that medications can only fulfill their therapeutic potential if individuals consistently adhere to their prescribed dosage and schedule. The repercussions of medication nonadherence in schizophrenia are multifaceted and extend across various domains, including clinical, social, and economic.

Clinical Impacts

Nonadherence with antipsychotic medications among persons with schizophrenia often leads to an increased risk of relapse, which can result in:

• Reemergence and exacerbation of symptoms
• Self-harm, including attempted or completed suicide
• Hospitalization or other acute intervention⁸

Moreover, relapse can lead to faster progression of brain mass reduction and diminished treatment acceptance, wherein the disorder becomes less responsive to pharmacotherapy, thereby complicating subsequent therapeutic interventions and necessitating higher doses of medication or alternative therapeutic approaches to achieve symptom reduction and support improved functioning and quality of life.⁹

Social Impacts

Nonadherence to prescribed medications can adversely affect persons with schizophrenia, as well as their support systems. For example, nonadherence can:

• Strain relationships with family members, friends, and caregivers, leading to increased tension and conflict within interpersonal dynamics at a time when patients especially need support.
• Lead to erratic behavior resulting from untreated symptoms – The behavior may be misunderstood or interpreted negatively by others, leading to disrupted relationships, social ostracization or avoidance, and sometimes even justice system involvement.
• Exacerbate social isolation – Misconceptions about schizophrenia may cause persons with schizophrenia to isolate, experience feelings of loneliness, and refrain from engaging in community activities. Nonadherence only creates additional barriers, leading to further isolation.¹⁰
• Heighten stress and burden among family members and caregivers as they attempt to navigate the challenges associated with supporting a loved one who is experiencing adherence difficulties.

Schizophrenia can be a lonely disease. Addressing medication nonadherence requires a comprehensive approach that seeks to promote social inclusion and provide support for both persons with schizophrenia and those around them.

Economic Impacts

Between 2013 and 2019, the estimated economic burden of schizophrenia grew within the US from an estimated $156 billion to $343 billion. The estimated costs were 73.4% attributable to indirect costs (e.g., caregiving, premature mortality, and unemployment), 18.2% due to direct health care costs (e.g., inpatient and emergency care), and 10.2% due to direct non-health care costs (e.g., housing insecurity and justice system involvement).²

Overall, the economic ramifications of medication nonadherence in schizophrenia underscore the importance of understanding the factors influencing nonadherence and implementing interventions to enhance treatment adherence.

Factors Influencing Medication Nonadherence: Identifying the Barriers

While medication nonadherence is a problem with all chronic conditions, it can be even more common among patients with psychiatric disorders due to unique patient, condition, and medication attributes that make adherence more difficult. For schizophrenia, the reported range of non-adherence varies widely from 4% to 72%, but the estimated mean rate is closer to 50%.^5,6

For adults 18 years or older who are insured through commercial, Medicaid, or Medicare plans, performance on the National Committee for Quality Assurance’s HEDIS quality measure, “Adherence to Antipsychotic Medications for Individuals with Schizophrenia,” was reported at rates ranging from 59.8% to 78.4% for Measure Year 2022, indicating significant opportunities exist for better adherence.¹¹

There are multiple factors that may contribute to persons with schizophrenia unintentionally and/or intentionally skipping doses, taking incorrect doses, or discontinuing their medications. Below are summaries of some of the patient/disease-related and environmental/social factors and their associated barriers.

Patient and Disease-Related Factors

Symptom Severity: Studies have shown that schizophrenia symptom severity is negatively correlated with adherence.¹² That is, increased symptom severity is associated with decreased adherence. The cognitive impairments and distorted perception of reality associated with schizophrenia can lead to difficulties with remembering to take medication or following complex dosing schedules, which can sometimes lead patients to believe they do not require treatment or that their treatment is ineffective.

In addition, the negative symptoms of schizophrenia, such as apathy and reduced drive, may lead patients to lose motivation to adhere to treatment. It is important to note that schizophrenia symptoms and nonadherence hold a bidirectional relationship wherein symptoms potentially lead to nonadherence, but then nonadherence leads to worsening symptoms, ultimately resulting in increased morbidity, mortality, and health care resource utilization, including hospitalization.

Adverse Events: Antipsychotic medications commonly prescribed for schizophrenia can cause significant AEs, including weight gain, sedation, and movement disorders.¹³ Such AEs may discourage individuals from adhering to their medication regimen, as patients may perceive the negative effects as outweighing the benefits of treatment.

Lack of Insight: Sometimes referred to as “anosognosia,” definitions of “insight” continue to evolve, and insight has been referred to as “understanding one’s illness and the social consequences of the disorder.”¹⁴

Estimates show that at least half of persons with schizophrenia experience anosognosia with fluctuating awareness of their condition. When individuals lack insight, they may exhibit poor adherence to treatment because they do not realize they have a treatable condition. From patients’ perspectives, one study of patients with schizophrenia who were assessed to be non-adherent reported that 37% of the patients expressed that they did not have an illness, that they did not need medications for their illness, and/or that they would not get better by taking medication.¹⁵

Research of the assessment and causes for lack of insight is increasing, and present research suggests that absence of insight can stem from factors such as inadequate education or, as mentioned previously, the cognitive impairments associated with the disorder itself.¹⁶

Environmental and Social Factors

Social Determinants of Health (SDOH): The American Association of Psychiatric Pharmacists (AAPP) appointed an expert panel to identify SDOH barriers impeding medication adherence among persons with psychiatric conditions. Barriers identified included lack of access to healthy food (e.g., some antipsychotics should be taken with food to boost absorption); unsafe housing conditions like inadequate air quality and ventilation (e.g., some medications used for schizophrenia treatment are associated with vulnerability to heat-related illness); and transportation barriers to accessing care and therapies (e.g., long-acting injectable medications).^17,18

Stigma: According to the World Health Organization (WHO), schizophrenia ranks among the most widely misunderstood behavioral health conditions. Persons with schizophrenia frequently encounter violations of their human rights, occurring both within health facilities and within their communities.¹⁹

The stigma surrounding this condition is pervasive and severe, leading to significant social discrimination against those affected, making individuals with schizophrenia often reluctant to believe that they have the illness or to seek medical treatment for it. Studies have also shown that feelings of embarrassment about taking medication among individuals with schizophrenia also lead to treatment abandonment.²⁰

Poor Support: In the face of stigma and discrimination, emotional support from family, friends, and support groups can provide individuals with schizophrenia a sense of belonging and reduce feelings of loneliness. Additionally, having practical support for tasks such as scheduling appointments, picking up prescriptions, and remembering to take medications can be beneficial. On the other hand, the absence of such assistance and supervision can increase the likelihood of medication nonadherence.²¹

Patient-Centered Approaches to Support Adherence

Improving medication adherence among individuals with schizophrenia presents a complex challenge due to the unique nature of the condition and its treatment. Addressing medication nonadherence requires a multifaceted approach that considers the interplay of biological, psychological, social, and environmental influences affecting an individual's treatment adherence. Here are some steps the health care ecosystem can take to support better adherence.

Education Is Empowerment

Patients, families, and friends can benefit from learning about schizophrenia and treatment options. Understanding the nature of the condition, the importance of medication and treatment options, and potential AEs can help with selection of treatment choices and with communication between patients, families, clinicians, peer support coaches, health systems, and health plans. There are now a range of digital health interventions patients and families may select from to improve medication adherence, including mobile apps, sensors, and web-based platforms. These tools provide medication-related information, reminders, monitoring, and other illness management suggestions.^22,23

Clinicians, pharmacists, peer support coaches, health systems, and health plans can use shared decision-making (SDM) aids to inform patients and families about schizophrenia, including symptoms and available therapies. Described as a “process where the patient and the health professional collaborate to make decisions based on both the patient’s preferences and the best available evidence,” SDM is associated with patient satisfaction and empowerment; is congruent with the values of patient-centered mental health recovery; and offers promise for better medication adherence, particularly for adoption of and adherence with long-acting injectable antipsychotics (LAIs).

This is especially noteworthy, given that The National Council Medical Director Institute now asserts that first-episode psychosis is an optimal time for education about LAIs due to their potential to reduce relapse frequency and to reduce the degenerative impact of relapse on brain and function.^24,25,26,27

Life science companies can support patients and families by supplying resources to facilitate their understanding of schizophrenia as well as treatment/recovery options and their respective potential benefits and AEs. For example, they can develop tools to help patients and their care partners become familiar with the medications being used, including names, dosages, and purposes. They can offer resources to care partners for encouraging adherence, customized to factors such as the patient’s age, motor abilities, symptom severity, and ability to actively manage their medication, which may fluctuate. Such resources can be customized even further by deploying an array of media that align with patient and families’ learning preferences, levels of health literacy, language, and culture.

Furthermore, life science companies can provide clinicians, peer support coaches, health systems, and health plan tools to advance patient and family understanding of schizophrenia, including decision aids, SDM best practices, and training. Life science companies can support patients and families by supplying resources to facilitate their understanding of schizophrenia as well as of treatment/recovery options and their respective potential benefits and side effects. For example, they can develop tools to help patients and their care partners become familiar with the medications being used, including names, dosages, and purposes.

They can also offer resources to care partners for encouraging adherence, customized to factors such as the patient’s age, motor abilities, symptom severity, and ability to actively manage their medication, which may fluctuate. Such resources can be customized even further by deploying an array of media that align with patient and families’ learning preferences, levels of health literacy, language, and culture.

Furthermore, life science companies can provide clinicians, peer support coaches, health systems, and health plans tools to advance patient and family understanding of schizophrenia, including decision aids, SDM best practices, and training for forging and sustaining recovery-oriented treatment teams with patients and their families at the center.

Maintaining Motivation

Patients, families, and friends can benefit from support groups where they can share strategies for medication adherence and reducing relapse, exchange emotional support, and problem-solve with others who have similar experiences. Peer support is beneficial for various medical conditions, including schizophrenia, by bolstering disease acceptance and social support.²⁸

Building and sustaining life-long motivation for a recovery lifestyle can be boosted by peer support.²⁹ Additionally, patients and their support systems may wish to seek out cognitive behavior therapy, an evidence-based psychotherapy that helps individuals with schizophrenia improve coping with symptoms, community integration, medication adherence, and overall quality of life.³⁰

Clinicians, pharmacists, peer support coaches, health systems, and health plans can help patients and families sustain motivation and improve quality of life by collaborating with patients and their families to identify and problem-solve to address SDOH that may serve as barriers to adherence and recovery (e.g., adequate food, transportation, housing). For example, individuals with transportation barriers may benefit from telehealth, which is gaining increased acceptance by individuals with schizophrenia and has been demonstrated as an effective medium for treatment. Providers should look to increase and improve telehealth options to minimize barriers to care and nonadherence.³¹

Complex medication regimens and AEs can also diminish motivation to continue regularly taking medications. For individuals with schizophrenia, cognitive impairment can greatly affect their ability to adhere to complex medication schedules. Long-acting formulations streamline medication routines and can improve medication adherence rates to the 80-90% range.¹² By making medication instructions and therapy schedules as straightforward as possible, providers can help mitigate the stress associated with complex regimens, reduce the chances of missed or incorrect medication usage, and help sustain self-efficacy and recovery confidence.

Finally, members of the treatment team can use motivational interviewing (MI) methods to help patients tap into their intrinsic motivations for adherence and recovery. Patients and families can also be instructed in MI to help them practice these methods to sustain their own and loved ones’ recovery motivations within their family and other social support systems.

Life science companies can assist patients, families, and providers through precision medicine (research and innovation in areas such as biomarker identification and treatment innovation) and through precision messaging to reduce stigma and improve condition acceptance and activation. For example, life science companies can participate in public-private partnerships (e.g., Accelerating Medicines Partnership Program for Schizophrenia, or AMP SCZ) to expedite research on biomarkers for precision medicine and the development of new treatments to prevent, mitigate, or end schizophrenia symptoms.³²

The COVID-19 pandemic has vividly demonstrated the important shortcomings of precision messaging to engage, inform, motivate, and sustain adherence and trust in the era of mass mis/disinformation. The life science industry, long known for its marketing acumen, must dedicate additional resources to precision messaging. As Francis Collins, MD, PhD, noted when reflecting on his career at the National Institutes of Health, “You know, maybe we underinvested in research on human behavior.”³³

A more sophisticated understanding of population segmentation can potentially be gained through social listening, focus groups, and awareness of influencer network social segmentations.^34,35,36,37 This greater awareness of how social networks are segmented will lead to more finely tuned, segment-oriented adherence messages; more engaged, proactive messenger networks; and improved artificial intelligence interfaces.

Takeaways

There are effective strategies that can be employed concurrently to promote adherence, including but not limited to pharmacological, technological, and psychosocial interventions. The health care ecosystem, including patients, family members, providers, pharmacists, and quality professionals, as well as health systems, health care plans, and life science organizations, all contribute to the collective effort of enhancing medication adherence, ultimately leading to better treatment outcomes and quality of life for individuals with schizophrenia.

References

1. Correll CU, Solmi M, Croatto G, et al. Mortality in people with schizophrenia: A systematic review and meta‐analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022;21(2): 248–271. doi:10.1002/wps.20994
2. Kadakia A, Catillon M, Fan Q, et al. The economic burden of schizophrenia in the United States. The Journal of Clinical Psychiatry. 2022;83(6). doi:10.4088/jcp.22m14458
3. Schizophrenia. National Institute of Mental Health. Accessed May 2024. https://www.nimh.nih.gov/health/topics/schizophrenia#part_2275
4. Fabrazzo M, Cipolla S, Camerlengo A, Perris F, Catapano F. Second-generation antipsychotics' effectiveness and tolerability: A review of real-world studies in patients with schizophrenia and related disorders. Journal of Clinical Medicine. 2022;11(15): 4530. doi:10.3390/jcm11154530
5. Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia. The Journal of Clinical Psychiatry. 2002;63(10): 892–909. doi:10.4088/jcp.v63n1007
6. Martin A, Bessonova L, Hughes R, et al. Systematic review of real-world treatment patterns of oral antipsychotics and associated economic burden in patients with schizophrenia in the United States. Advances in therapy. 2022;39(9): 3933–3956. doi:10.1007/s12325-022-02232-z
7. Pope, C. List of atypical antipsychotics. Drugs.com. Updated April 14, 2023. Accessed May 2024. https://www.drugs.com/drug-class/atypical-antipsychotics.html
8. Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. The Journal of Clinical Psychiatry. 2006;67(5): 3-8.
9. Pandey A, Kalita KN. Treatment-resistant schizophrenia: How far have we traveled? Frontiers in Psychiatry. 2022;13. doi:10.3389/fpsyt.2022.994425
10. Oliveira SE, Esteves F, Carvalho H. Clinical profiles of stigma experiences, self-esteem and social relationships among people with schizophrenia, depressive, and bipolar disorders. Psychiatry Research. 2015;229(1-2):167-73. doi:10.1016/j.psychres.2015.07.047
11. Adherence to antipsychotic medications for individuals with schizophrenia. National Committee for Quality Assurance (NCQA). https://www.ncqa.org/hedis/measures/adherence-to-antipsychotic-medications-for-individuals-with-schizophrenia/
12. Acosta FJ. Medication adherence in schizophrenia. WJP. 2012;2(5):74. doi:10.5498/wjp.v2.i5.74
13. Medication for schizophrenia. NYU Langone Health. 2024. https://nyulangone.org/conditions/schizophrenia/treatments/medication-for-schizophrenia
14. What to know about anosognosia. MedicalNewsToday. March 31, 2022. Updated December 6, 2023. https://www.medicalnewstoday.com/articles/anosognosia
15. Z N, Muraraiah S, H C. Medication adherence in schizophrenia: Understanding patient's views. Natl J Physiol Pharm Pharmacol. 2019:1. doi:10.5455/njppp.2019.9.0206002032019
16. Ullah MA, Zohra F, Sarkar M, Ahmed AU. Impaired insight and its implications in schizophrenia. Archives of NIMH. 2018;1(1): 23–28.
17. Smith-East, M. Medication with food: What does it really mean?. American Nurse. August 14, 2019. https://www.myamericannurse.com/medication-with-food-what-does-it-really-mean/
18. New study finds people with schizophrenia were at higher risk during B.C.’s 2021 Heat Dome. BC Centre for Disease Control. March 16, 2023. http://www.bccdc.ca/about/news-stories/stories/2023/schizophrenia-risk-heat
19. Schizophrenia. World Health Organization. January 10, 2022. https://www.who.int/news-room/fact-sheets/detail/schizophrenia
20. Hui CL, Chen EY, Kan C, Yip K, Law C, Chiu CP. Detection of Non-Adherent Behaviour in Early Psychosis. Aust N Z J Psychiatry. 2006;40(5):446-51. doi:10.1080/j.1440-1614.2006.01821.x
21. Semahegn A, Torpey K, Manu A, Assefa N, Tesfaye G, Ankomah A. Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis. Syst Rev. 2020;9(1). doi: doi.org/10.1186/s13643-020-1274-3
22. Wu T, Xiao X, Yan S, et al. Digital health interventions to improve adherence to oral antipsychotics among patients with schizophrenia: a scoping review. BMJ Open. 2023;13(11):e071984. doi:10.1136/bmjopen-2023-071984
23. Acala M. Improving medication adherence in individuals with psychiatric illnesses. [Doctoral dissertation, Rutgers University]. 2022. doi:10.7282/t3-2jp1-9m82
24. Guide to long-acting medications for clinicians & organizations. National Council for Mental Well-Being. December 13, 2021. Accessed February 2, 2022. https://www.thenationalcouncil.org/resources/guide-to-long-acting-medications/
25. Haugom EW, Stensrud B, Beston G, Ruud T, Landheim AS. Experiences of shared decision making among patients with psychotic disorders in Norway: a qualitative study. BMC Psychiatry. 2022;22(1): 192. doi:10.1186/s12888-022-03849-8
26. Hamtann J, Holzhüter F, Blakaj S, et al. Implementing shared decision-making on acute psychiatric wards: a cluster-randomized trial with inpatients suffering from schizophrenia (SDM-PLUS). Epidemiology and psychiatric sciences. 2020;29: e137. doi:10.1017/S2045796020000505
27. Psychosis and schizophrenia in adults: prevention and management. London: National Institute for Health and Care Excellence (NICE); 2014 Mar. (NICE Clinical Guidelines, No. 178.) https://www.ncbi.nlm.nih.gov/books/NBK555203/
28. Caselein S, Bruggeman R, Davidson L, Gaag M van. Creating a supportive environment: Peer Support Groups for psychotic disorders. Schizophrenia Bulletin. 2015;41(6): 1211–1213. doi:10.1093/schbul/sbv113
29. Peers Supporting Recovery from Mental Health Conditions. SAMHSA. November 20, 2017. https://www.samhsa.gov/sites/default/files/programs_campaigns/brss_tacs/peers-supporting-recovery-mental-health-conditions-2017.pdf
30. Cronkleton E. What to know about CBT for schizophrenia. Medical News Today. January 11, 2022. https://www.medicalnewstoday.com/articles/cbt-for-schizophrenia
31. Santesteban-Echarri O, Piskulic D, Nyman RK, Addington J. Telehealth interventions for schizophrenia-spectrum disorders and clinical high-ri.sk for psychosis individuals: A scoping review. Journal of Telemedicine and Telecare. 2018;26(1–2): 14–20. doi:10.1177/1357633x18794100
32. Accelerating medicines partnership® program for schizophrenia (AMP® SCZ). National Institute of Mental Health. November 2022. https://www.nimh.nih.gov/research/research-funded-by-nimh/research-initiatives/accelerating-medicines-partnershipr-program-schizophrenia-ampr-scz
33. Dr. Collins reflects on career at NIH, covid response effort, work on Genome Sequencing. Public Broadcasting Service. PBS. December 20, 2021. https://www.pbs.org/newshour/show/dr-collins-reflects-on-career-at-nih-covid-response-effort-work-on-genome-sequencing.
34. Hennessey M, Caputo P. Assessing and addressing social determinants of health (SDOH) during a pandemic. Social determinants of health webinar series, part 2, slides 16-19. PRECISIONvalue and PRECISIONeffect. December 2, 2020. Accessed April 23, 2024. https://event.on24.com/wcc/r/2806924/FE0E4A0C5D64B520C0ABDC6BF1B77BB
35. Oyekan E, Hennessey M, Galante D, Miller C, Font J. Bringing social determinants of health to life to optimize health outcomes in patients with chronic conditions. Journal of Clinical Pathways. 2022;8(1). doi:10.25270/jcp.2022.02.3
36. Song Y, Liu D, Chen Y, He G. Using focus groups to design a psychoeducation program for patients with schizophrenia and their family members. International journal of clinical and experimental Medicine, 2014;7(1): 177–185.
37. Smith E, Ibanez A, Lavretsky H, Berk M, Eyre HA. Psychographic segmentation: Another lever for precision population brain health. Frontiers in Aging Neuroscience. 2021;13: 783297. doi:10.3389/fnagi.2021.783297