Real-World Insights Into Unmet Needs Among Patients With Schizophrenia

SupplementsPain Live® - June 2022 Newsletter

This article is sponsored by Teva Pharmaceuticals.

Recently a panel of psychiatrists, nurse practitioners, people living with schizophrenia and their caregivers convened to engage in a dynamic exchange from different viewpoints within the schizophrenia community. Panelists participated in an experience-based conversation regarding their own management of schizophrenia and barriers to care, shedding light on overall disease burden and unmet needs. The following summarizes key highlights and findings from the panel, which underscore the importance of education for patients, healthcare providers and broader society to support public health initiatives around mental illness.


Schizophrenia is a psychiatric condition characterized by hallucinations, delusions, and disorganized speech.1 The causes of schizophrenia are complex and not well understood, although there are neurobiological, genetic, and environmental factors involved.1 The condition is often diagnosed when individuals first display symptoms in an episode of psychosis; this often occurs during late adolescence and in young adults under 25 years of age.1 Symptoms generally fall into three categories: psychotic (hallucinations, delusions, thought disorders), negative (loss of motivation, disinterest, lack of enjoyment, social withdrawal), and cognitive (issues with attention/concentration, learning, memory, processing information, and decision-making).1

The prevalence of diagnosed schizophrenia in the United States is approximately three to five per 1000 people, one of the top 15 causes of disability worldwide.2-4 Individuals with schizophrenia have an increased risk of premature mortality, with an average of 28.5 potential years of life lost. Related mortality risk factors include co-occurring medical conditions (eg, heart disease, liver disease, diabetes) that are underdetected and undertreated and higher rates of suicide than the general population, particularly during the early stages of disease.5 Individual patients may have a variable presentation of schizophrenia symptoms that requires personalized approaches for effective management.6 Approaches typically include use of antipsychotic medications, which can help reduce the intensity and frequency of psychotic symptoms.7 However, patients may be reluctant to continue medication when their disease stabilizes, and many will experience relapse.1


Generally, relapse in patients with schizophrenia is characterized by sudden exacerbations of symptoms and psychotic episodes that may require hospitalization.8 These episodes of untreated psychosis may contribute to disabling cognitive and functional decline, from which patients may not fully recover. Relapse rates range between 41% and 96% globally.9 Lack of adherence to treatment with oral antipsychotics is the most common cause of relapse.10

Relapses are associated with a progressive decline in brain volume, and studies have demonstrated a loss of more than one percent of total brain volume—about a tablespoon—and a loss of up to three percent of gray matter volume within one to two years following.11 Relapse can lead to cognitive impairment with long-term implications, including:10,12,13

  • Increased risk of harm to self or others
  • Increased strain on personal relationships
  • Difficulty in maintaining jobs
  • Difficulty in completing education
  • Increased resistance to treatment
  • Reduction in treatment efficacy

Preventing relapse is an important goal of schizophrenia management. Relapse affects adult patients with schizophrenia as well as their personal relationships with those in their connected care team. Because of the correlation between nonadherence and relapse, choosing therapies associated with improved adherence rates is a priority.14


Nonadherence, according to medical literature, is defined as a patient missing at least 20% of medication dosing in a specific period of time.15 The causes of nonadherence generally fall into these two categories15:

  • Intentional: patients make a conscious decision not to follow their treatment recommendations
  • Unintentional: patients want to follow the agreed upon treatment plan but are unable to do so because they lack skills or the ability to take their medication correctly (eg, forgetfulness, difficulty following instructions)

There are a variety of patient-related and healthcare provider (HCP)–related factors that contribute to treatment nonadherence, such as:16

  • A negative attitude toward treatment, including stigmatization of the disease and shame for taking medication
  • Drug or alcohol use
  • Content of psychotic symptoms (delusions of persecution or poisoning)
  • Lack of support from family and friends
  • Poor relationships with medical professionals and negative experiences during hospitalizations

The panelists shared the barriers to treatment and adherence that they have experienced as patients or observed as clinicians and identified potential strategies to overcome them.


The patients on the panel expressed experiencing difficulty in finding the appropriate treatment plan; there is no one-size-fits-all therapy.15 Among the most frequently reported reasons for patient dissatisfaction with medication is lack of patient and/or caregiver involvement in care plan development.15 Sometimes, HCPs have misconceptions about patient preferences and do not discuss different treatment options with their patients.15 Poor communication and lack of a positive therapeutic relationship between patients and HCPs has been correlated with a higher risk of nonadherence.14,16

The panelists shared their personal strategies for staying adherent to medication, reflecting on their postrelapse state. Personal motivations of not wanting to experience another relapse due to challenges during a psychotic episode were noted. Another patient panelist discussed how she needed to use her organizational skills to develop habits and adhere to her daily oral medication regimen, especially because multiple medications were involved. Given the cognitive impairment that patients with schizophrenia may experience, this could be challenging.1,14,17

Complex medication regimens of antipsychotic polypharmacy, higher dosing frequency, and complicated instructions for drug-taking may discourage patients from taking oral medications.14,17 Data from studies of patients with chronic illnesses have shown a correlation between the use of multiple medications and lower adherence, which, in turn, resulted in poor outcomes.14,17

Patients on the panel shared some of the burdens their disease presents in their daily lives, particularly in regards to family and other personal relationships, such as difficulty developing and maintaining friendships. To overcome this barrier, patients and caregivers can work together to closely monitor symptom progression and identify and neutralize any triggers (eg, schedule adjustments, distraction, stressful interactions) that may lead to more severe symptoms and potential relapses.1,14,18,19

Family or caregiver attitudes and degree of understanding or education about schizophrenia can affect the level of support that they are able to provide patients with schizophrenia. Asking a family member or caregiver to monitor use of an oral medication for a patient can be burdensome to family dynamics, and it may strain relationships.20-22 Lack of support from family and caregivers has been linked with a higher risk of relapse and a negative course of disease progression.20,21,23 One patient panelist said that his family was unaware and uneducated about schizophrenia and couldn’t provide adequate support, going so far as to withhold his daily oral medication. Another participant said that her family had a history of schizophrenia; consequently, she believed that their experience and knowledge of the disease equipped them to be supportive to her.


As observed by the patient panelists, the providers on the panel acknowledged selection of the appropriate medication and dosing schedule for individuals diagnosed with schizophrenia can be difficult and can take time.1,15

The effectiveness and safety profiles of antipsychotic medications vary considerably.1,15 As such, the provider panelists observed that patients are less likely to adhere to a therapeutic regimen if the adverse events (AEs) experienced are more burdensome than the disease itself, such as weight gain and extrapyramidal effects.1,15 AEs that are associated with some treatments may be a barrier to adherence, especially when symptoms are not well-managed.1,15 Therefore, the development of more tolerable antipsychotic agents is also an important need.1


Guidelines for the treatment of patients with schizophrenia from the American Psychiatric Association (APA), updated in 2020, emphasize a patient-centered treatment plan that includes evidence-based nonpharmacologic and pharmacologic treatments.18 Pharmacological treatments can include oral antipsychotic medications and long-acting injectable (LAI) antipsychotic medications.10,24

Patient-centric care and a connected, multidisciplinary care team could help support patients and their caregivers in their management of this disease.14,17 The panelists identified several strategies to prevent relapses and improve the quality of care for patients with schizophrenia, including:10,14-16,18,24

  • Shared decision-making between HCPs, patients, and caregivers
  • Comprehensive treatment plans that include holistic options and education, direction, and motivation so that patients can live productive, independent, and fulfilling lives
  • Discussing treatment options to identify appropriate medication and considering the use of LAI antipsychotic medication


LAI antipsychotic medications have the potential to reduce treatment nonadherence and discontinuation.10,24 These agents are available in several administration schedules, including biweekly, monthly, every six weeks, and every three months.1 LAIs could ease the burden of daily medication, help facilitate regular contact between patients and their healthcare teams, allow HCPs to recognize when patients do not take their medication so that they can intervene appropriately, and potentially reduce the burden on caregivers who may be tasked with ensuring that patients take their medications.25,26

Recent updates to the APA guidelines for schizophrenia include recommendations for LAIs if the injectables are preferred by the patient, if the patient has a history of poor adherence or uncertain adherence to oral therapy, and/or if it is deemed necessary by the HCP and the patient’s future adherence to oral medications is questionable or uncertain.18 These agents remain underused in real-world clinical practice, in part because clinicians may have inaccurate perceptions about LAIs and their patients’ attitudes toward them.10,16,27 Results from a real-world, cross-sectional survey of psychiatrists in the United States showed that LAIs primarily are prescribed to patients who have had repeated hospitalizations due to relapses.28 However, there is a growing body of evidence demonstrating the use of LAIs over oral antipsychotics in first-episode or early-phase schizophrenia.29

Compared with oral antipsychotic medications, LAI medications offer an extended time to relapse, emergency department visits, and hospital admissions.29 In the recent US-based PRELAPSE (NCT02360319) multicenter, randomized, phase 4 trial that involved patients with less than a year of antipsychotic use, administration of the once-monthly LAI aripiprazole substantially delayed time to first hospitalization compared with the clinician’s chosen treatment among any FDA-approved antipsychotic medication. The use of LAIs in patients with early-phase schizophrenia can substantially delay first hospitalization.30 In addition, a longer time to relapse can provide patients with benefits that include the ability to work, sustain housing, socialize, and attend school.10,14,15,29,31

Shared Decision-Making

For HCPs, it is helpful to involve patients in a collaborative way to make an informed decision. Some patients lack insight about their disease and need education. HCPs should speak with patients (not at them) to educate about treatment option benefits and risks, address patient misconceptions, and empower patients with choices about their treatment plan. HCPs can also identify a treatment regimen that accounts for preferences of patients, understanding of maintenance, and tendencies toward adherence.10,14,15,31 In addition, HCPs should discuss all treatment options, including initiating treatment with an LAI if oral regimens are not helping patients achieve their own goals.31 One of the patient panelists explained that she is motivated to stay adherent to her medication because she remembers how she felt during a psychotic episode and wants to avoid experiencing another relapse. However, not all patients have this level of motivation, and those individuals may benefit from an LAI.


The providers on the panel indicated that they have personally observed other HCPs focusing only on the use of antipsychotic agents rather than incorporating holistic strategies into a patient’s treatment plan.15 Treatment can only help manage symptoms to a certain degree, so patients must learn to live with schizophrenia.15 In addition to recommending that patients with schizophrenia be treated with antipsychotic medication, the APA suggests that patients with this diagnosis receive interventions aimed at developing self-management skills and enhancing person-oriented recovery, cognitive remediation, and social skills.18

The panelists also suggested that providing education to family members and caregivers to improve their understanding and awareness of the disease could relieve relationship strain and help prevent stressful situations that may lead to nonadherence or trigger a relapse.15


Adults living with schizophrenia experience stigma from society, which often interferes with their ability to maintain close relationships with family and friends and function within social settings.32,33 The patients on the panel emphasized the importance of having social interactions and relationships with people outside their family and caregivers. One study showed that patients with schizophrenia had a small network of friends, yet those friendships were mostly positive and highly valued.34

Positive media representations of adults living with schizophrenia may also help support destigmatizing the disease.34 For example, negative depictions of the condition in entertainment and media, which sometimes cover crime involving patients with the disease, can misinform the public about the nature of schizophrenia and lead to negative perceptions of these patients.35,36

The panelists highlighted the need to improve mental health education and literacy in society to reduce the stigma and increase understanding of schizophrenia and other mental health conditions.32,37,38 Mental health literacy education, starting with children and adolescents in schools, could help destigmatize mental illness and support early interventions.38-41 As noted by a patient panelist, mental health literacy strategies should account for cultural differences in attitudes about mental illness and approaches to disease management.35 The patients on the panel said that relapse prevention and symptom reduction should not be the focus of only HCPs; patients with schizophrenia need to feel empowered to engage with these goals, which can lead to living independent, satisfying, and productive lives.41,42

Finding a medication the patient can adhere to consistently to help prevent relapse may be the first step toward these goals. Education around LAIs is also specifically needed. Use of LAIs may help reduce relapse rates among patients living with schizophrenia, but many HCPs overestimate their patients’ fears about or resistance to them.10,16,19,24 HCPs should educate patients about LAIs and other antipsychotics as part of the shared decision-making process.16


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  11. Cahn W, Hulshoff Pol HE, Lems EB, et al. Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry. 2002;59(11):1002-1010. doi:10.1001/archpsyc.59.11.1002
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  16. Acosta FJ, Hernández JL, Pereira J, Herrera J, Rodríguez CJ. Medication adherence in schizophrenia. World J Psychiatry. 2012;22:2(5):74-82. doi:10.5498/wjp.v2.i5.74
  17. Fleischhacker WW, Uchida H. Critical review of antipsychotic polypharmacy in the treatment of schizophrenia. Int J Neuropsychopharmacol. 2014;17(7):1083-1093. doi:10.1017/S1461145712000399
  18. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872. doi:10.1176/appi.ajp.2020.177901
  19. Cahling L, Berntsson A, Bröms G, Öhrmalm L. Perceptions and knowledge of antipsychotics among mental health professional and patients. BJPsych Bull. 2017;41(5):254-259. doi:10.1192/pb.bp.116.055483
  20. Lippi G. Schizophrenia in a member of the family: burden, expressed emotion and addressing the needs of the whole family. S Afr J Psychiatr. 2016;22(1):922. doi:10.4102/sajpsychiatry.v22i1.922
  21. Kamil SH, Velligan DI. Caregivers of individuals with schizophrenia: who are they and what are their challenges? Curr Opin Psychiatry. 2019;32(3):157-163. doi:10.1097/YCO.0000000000000492
  22. Caqueo-Urízar A, Rus-Calafell M, Craig TKJ, et al. Schizophrenia: impact on family dynamics. Curr Psychiatry Rep. 2017;19(1):2. doi:10.1007/s11920-017-0756-z
  23. Caqueo-Urízar A, Rus-Calafell M, Urzúa A, Escudero J, Gutiérrez-Maldonado J. The role of family therapy in the management of schizophrenia: challenges and solutions. Neuropsychiatr Dis Treat. 2015;11:145-151. doi:10.2147/NDT.S51331
  24. Greene M, Yan T, Chang E, Hartry A, Touya M, Broder MS. Medication adherence and discontinuation of long-acting injectable versus oral antipsychotics in patients with schizophrenia or bipolar disorder. J Med Econ. 2018;21(2):127-134. doi:10.1080/13696998.2017.1379412
  25. Stevens GL, Dawson G, Zummo J. Clinical benefits and impact of early use of long-acting injectable antipsychotics for schizophrenia. Early Interv Psychiatry. 2016;10(5):365-377. doi:10.1111/eip.12278
  26. Brissos S, Veguilla MR, Taylor D, Balanzá-Martinez V. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal. Ther Adv Psychopharmacol. 2014;4(5):198-219. doi:10.1177/2045125314540297
  27. Heres S. Long-acting injectable antipsychotics: an underutilized option. J Clin Psychiatry. 2014;75(11):1263-1265. doi:10.4088/JCP.14com09541
  28. Fitzgerald HM, Shepherd J, Bailey H, Berry M, Wright J, Chen M. Characterization and treatment goals of patients on long-acting injectable vs oral antipsychotics: results from a patient/caregiver/psychiatrist survey. CNS Spectr. 2021;26(2):154. doi:10.1017/S109285292000245X
  29. Correll CU, Citrome L, Haddad PM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1-24. doi:10.4088/JCP.15032su1
  30. Kane JM, Schooler NR, Marcy P, et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(12):1217-1224. doi:10.1001/jamapsychiatry.2020.2076
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  32. Schizophrenia. National Institute of Mental Health. Revised May 2020. Accessed November 18, 2021.
  33. Wood L, Birtel M, Alsawy, Pyle M, Morrison A. Public perceptions of stigma towards people with schizophrenia, depression, and anxiety. Psychiatry Res. 2014;220(1-2):604-608. doi:10.1016/j.psychres.2014.07.01
  34. Harley EWY, Boardman J, Craig T. Sexual problems in schizophrenia: prevalence and characteristics. a cross sectional survey. Soc Psychiatry Psychiatr Epidemiol. 2010;45(7):759-766. doi:10.1007/s00127-009-0119-0
  35. Srivastava K, Chaudhury S, Bhat PS, Mujawar S. Media and mental health. Ind Psychiatry J. 2018; 27(1):1-5. doi:10.4103/ipj.ipj_73_18:10.4103/ipj.ipj_73_18
  36. Owen PR. Portrayals of schizophrenia by entertainment media: a content analysis of contemporary movies. Psychiatr Serv. 2012;63(7):655-659. doi:10.1176/
  37. Jorm AF. Mental health literacy: empowering the community to take action for better mental health. Am Psychol. 2012;67(3):231-243. doi:10.1037/a0025957
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  39. Kelly CM, Jorm AF, Wright A. Improving mental health literacy as a strategy to facilitate early intervention for mental disorders. Med J Aust. 2007;187(S7):S26-S30. doi:10.5694/j.1326-5377.2007.tb01332.x
  40. Mcluckie A, Kutcher S, Wei Y, Weaver C. Sustained improvements in students’ mental health literacy with use of a mental health curriculum in Canadian schools. BMC Psychiatry. 2014;14:379. doi:10.1186/s12888-014-0379-4
  41. Mucci A, Galderisi S, Gibertoni D, et al; Italian Network for Research on Psychoses. Factors associated with real-life functioning in persons with schizophrenia in a 4-year follow-up study of the Italian Network for Research on Psychoses. JAMA Psychiatry. 2021;78(5):550-559. doi:10.1001/jamapsychiatry.2020.4614
  42. Chou KR, Shih YW, Chang C, et al. Psychosocial rehabilitation activities, empowerment, and quality of community-based life for people with schizophrenia. Arch Psychiatr Nurs. 2012;26(4):285-294. doi:10.1016/j.apnu.2012.04.003

March 2022

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