Real-World Effectiveness, Economic, and Humanistic Outcomes of Selected Oral Antipsychotics in Patients with Schizophrenia: A Systematic Review Evaluating Global Evidence

Keyuri Adhikari,1,* Khalid M Kamal,1,* Ki Jin Jeun,1 David A Nolfi,2 Mohammed Najeeb Ashraf,3 Christopher Zacker4 1Department of Pharmaceutical Systems and Policy, West Virginia University School of Pharmacy, Morgantown, WV, USA; 2Gumberg Library, Duquesne University, Pittsburgh, PA, USA; 3Medical Affairs, SciVoc Consulting Inc, Toronto, Ontario, Canada; 4Global Value & Access, Cerevel Therapeutics, Cambridge, MA, USA*These authors contributed equally to this workCorrespondence: Khalid M Kamal, Department of Pharmaceutical Systems and Policy, West Virginia University School of Pharmacy, Email [email protected]: Schizophrenia is a complex, chronic mental health disorder that confers a substantial disease burden globally. Oral antipsychotic treatments (OATs) are the mainstay for treating early and advanced stages of schizophrenia. Our systematic review aimed to synthesize literature describing real-world effectiveness, economic, and humanistic outcomes of OATs (asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine) for successful management of the disease.Methods: PubMed, American Psychological Association PsycINFO (EBSCOhost), and Cumulative Index of Nursing and Allied Health Literature were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting real-world effectiveness, costs, humanistic, behavioral (eg, interpersonal relations, suicide ideation), medication adherence, and product-switching outcomes for selected OATs published in English from January 2010 to March 2022 were identified and evaluated qualitatively.Results: We included 48 studies with different designs providing extensive evidence on schizophrenia. All studies were conducted in countries outside of the United States. In most studies, antipsychotic medications were more effective than placebo, suggesting their value in the management of schizophrenia. Sixteen studies measured the economic outcomes of OATs. Eight studies assessed humanistic outcomes, while one reported behavioral outcomes in three second-generation antipsychotics. Medication adherence was described in two studies, while five studies evaluated product switching. Non-adherence was commonly reported for OATs. Medication non-adherence and treatment discontinuation were predominant factors contributing to the economic burden of schizophrenia.Conclusion: Our research showcased a significant knowledge gap across OATs spanning the humanistic and behavioral outcomes and medication adherence and switching, suggesting a need for robust evidence generation to help clinicians and payers make informed decisions regarding treatment opportunities and cost-effective strategies for patients with schizophrenia.Keywords: schizophrenia, behavioral outcomes, cost-effectiveness, humanistic outcomes, medication adherence, product switchin

Quantifying the Tolerability of Antipsychotic Treatment-Related Side Effects in Schizophrenia: A Survey Study of Patients and Caregiver Proxies

Melissa Culhane Maravic,1 Kelly Birch,1 Anh Thy H Nguyen,1 Alicia Subasinghe,2 Elizabeth Stafford,3 Christopher Zacker2 1Precision AQ, New York, NY, USA; 2Cerevel Therapeutics, Cambridge, MA, USA; 3National Alliance on Mental Illness, Arlington, VA, USACorrespondence: Melissa Culhane Maravic, Precision AQ, 133 Federal Street, Boston, MA, 02110, USA, Email [email protected]: Antipsychotic medications are considered the mainstay of treatment for schizophrenia. However, these medications are associated with a wide range of side effects, which may be tolerated differently by patients, and may impact initiation and continuation of treatment.Purpose: This study aimed to assess the tolerability of antipsychotic medication side effects for patients with schizophrenia and understand how side effects may impact decisions to initiate and remain in treatment.Methods: A cross-sectional survey was conducted with 200 people living with schizophrenia and 100 caregiver proxies for those with severe disease presentation. The survey utilized the Maximum Difference Scaling (MaxDiff) approach to quantify preferences and a direct elicitation survey to rank specific side effects. Descriptive analysis and statistical analyses were conducted to address the study objectives.Results: Results indicated that extrapyramidal side effects such as pseudoparkinsonism and tardive dyskinesia, as well as feeling detached and memory and cognitive issues were ranked as the least tolerable. In contrast, side effects such as reduced interest in/enjoyment of sex, feeling tired or drowsy, and dry mouth were perceived as more tolerable. Caregivers’ perspectives closely aligned with the care recipients’ rankings, with an additional particular concern for high blood sugar that may lead to diabetes. Side effects such as pseudoparkinsonism, memory and cognitive problems, and weight gain were associated with unwillingness to initiate or continue an effective antipsychotic medication.Conclusion: These findings highlight the importance of considering side effect profiles when selecting and discussing treatment options with patients. Side effects can potentially impact patients’ willingness to start or switch medications, therefore, prescribing decisions should take into consideration patients’ tolerance for potential adverse effects. Engaging patients and caregivers in treatment decisions can enhance shared decision-making and treatment satisfaction. Healthcare providers should consider these findings when prescribing antipsychotic medications to people living with schizophrenia.Plain Language Summary: Schizophrenia is a disease that disrupts a person’s thought processes, perceptions, emotional responsiveness, and social interactions. Individuals living with schizophrenia generally require continuous psychiatric care, drug treatment, and other support services throughout their lives. Antipsychotic medications can help reduce symptoms of psychosis and psychiatric hospitalizations and can improve daily functioning. However, antipsychotics have a wide range of side effects, which makes regularly taking the medication less desirable. This study found that medications used for schizophrenia are highly bothersome, and people who take these medications may view side effects as a barrier to staying consistent with treatment. Side effects like having symptoms that imitate Parkinson’s disease, problems with feeling detached from one’s surroundings, problems with memory and cognition, and significant weight gain are of most concern to people living with schizophrenia. New antipsychotic treatments with minimal side effects would likely be well received by patients and may increase consistent treatment.Keywords: MaxDiff, direct elicitation, caregiving, treatment tolerability, treatment initiation, quantifying preference

Neuropsychological Characteristics of Young Adult Chronic Psychiatric Patients: Preliminary Observations

Psychological evaluation included tests of brain-behavior functioning and academic level for 110 young adults (16 to 39 yr. of age), each a moderate to heavy user of mental health services. The composite patient manifested borderline, diffuse brain dysfunction with deficiencies in language, visuospatial, motor, concentration, and higher-order problem-solving skills, together with below normal performance on tests of intelligence, reading comprehension, arithmetic calculation, and spelling. Standard mental health services appear inadequate for habilitation or rehabilitation of many such people. The findings suggest that one reason for these patients' lack of response to conventional mental health treatments is that clinicians fail to identify patients' fundamental deficiencies and to incorporate this knowledge in planning treatments and evaluating progress. Suggestions for further studies are offered. </jats:p

Perspectives on electronic medical records adoption: electronic medical records (EMR) in outcomes research

Dan Belletti1, Christopher Zacker1, C Daniel Mullins21Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2University of Maryland School of Pharmacy, Baltimore, MD, USAAbstract: Health information technology (HIT) is engineered to promote improved quality and efficiency of care, and reduce medical errors. Healthcare organizations have made significant investments in HIT tools and the electronic medical record (EMR) is a major technological advance. The Department of Veterans Affairs was one of the first large healthcare systems to fully implement EMR. The Veterans Health Information System and Technology Architecture (VistA) began by providing an interface to review and update a patient&amp;rsquo;s medical record with its computerized patient record system. However, since the implementation of the VistA system there has not been an overall substantial adoption of EMR in the ambulatory or inpatient setting. In fact, only 23.9% of physicians were using EMRs in their office-based practices in 2005. A sample from the American Medical Association revealed that EMRs were available in an office setting to 17% of physicians in late 2007 and early 2008. Of these, 17% of physicians with EMR, only 4% were considered to be fully functional EMR systems. With the exception of some large aggregate EMR databases the slow adoption of EMR has limited its use in outcomes research. This paper reviews the literature and presents the current status of and forces influencing the adoption of EMR in the office-based practice, and identifies the benefits, limitations, and overall value of EMR in the conduct of outcomes research in the US.Keywords: electronic medical records, health information technology, medical error

Association Between Persistence with Oral Atypical Antipsychotic Medications and Hospital and Emergency Department Utilization in Medicaid Patients with Schizophrenia

Kristin Richards,1 Michael Johnsrud,1 Christopher Zacker,2 Rahul Sasané2 1TxCORE, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA; 2Cerevel Therapeutics, LLC, Cambridge, MA, USACorrespondence: Kristin Richards, TxCORE, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Mail Stop A1930, Austin, TX, 78712, USA, Tel +1 512 471 5607, Email [email protected]: To examine 1-year persistence with oral atypical antipsychotics (OAAPs) for Medicaid patients with schizophrenia and assess the association between OAAP persistence and hospital and emergency department (ED) resource utilization.Patients and Methods: Using 2016– 2020 multi-state Medicaid claims data, this retrospective study followed patients diagnosed with schizophrenia for 12 months after initiating OAAP therapy. Patients started on an OAAP with no evidence of antipsychotic use in the previous 6 months were included if they had a diagnosis of schizophrenia, were not dually enrolled in Medicaid and Medicare, did not switch to a long-acting injectable antipsychotic, and were continuously eligible 6 months before and 12 months after the initial OAAP prescription (index date). OAAP persistence was measured allowing for a < 60-day gap. All-cause and schizophrenia-related inpatient and emergency department (ED) resource utilization during the follow-up period were compared between OAAP persistent and non-persistent groups.Results: The study sample of 13,007 had an average age of 39.1 years and 57.0% were male. Patients were persistent with their index OAAP for 135 days on average and 73.1% had a ≥ 60-day gap in antipsychotic therapy post-index. While 32.8% and 28.6% of patients who did not persist with their index OAAP restarted the index OAAP or switched to a different OAAP medication later in the year, respectively, a larger proportion (38.6%) had no further OAAP prescriptions. After adjustment for demographic and clinical variables, compared to non-persistent patients, persisting with OAAPs was significantly associated with fewer all-cause and schizophrenia-related hospitalizations (Incidence Rate Ratio [IRR]=0.742, p< 0.001; IRR=0.823, p< 0.001; respectively) and ED visits (IRR=0.759, p< 0.001; IRR=0.773, p< 0.001; respectively).Conclusion: Non-persistence with OAAP medication is common among patients with schizophrenia and associated with negative outcomes including increased utilization of hospital and ED resources. Patient-centered interventions that improve antipsychotic persistence should be implemented to facilitate optimal outcomes in this population.Keywords: antipsychotic medication, persistence, healthcare resource utilization, Medicaid, schizophreni