LB-102

The Global Burden of Disease Study 2021 estimated approximately 23.2 million people living with schizophrenia worldwide (about 0.3% of the global population) and approximately 1.2 million incident cases in 2021, with an age-standardized incidence rate of 15.4 per 100,000. United States estimates differ by method and population. The National Institute of Mental Health reports a prevalence of schizophrenia and related psychotic disorders between 0.25% and 0.64% across studies that use household-based survey samples, clinical diagnostic interviews, and medical records. The Mental and Substance Use Disorders Prevalence Study, which administered a structured clinical interview to 5,679 participants aged 18 to 65 in households, prisons, homeless shelters, and state psychiatric hospitals between October 2020 and October 2022, estimated past-year prevalence of schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, and schizophreniform disorder) at 1.2% (approximately 2.5 million adults) and lifetime prevalence at 1.8% (approximately 3.7 million adults). A weighted national claims analysis for 2022 estimated the diagnosed prevalence of schizophrenia at 0.45% (1.10% in Medicare fee-for-service, 1.10% in Medicare Advantage, 0.91% in Medicaid, and 0.07% in commercial insurance) and its incidence at 0.08%. A second claims study reported a prevalence of 2.13% in Medicaid (94,153 of 4,414,153) and 0.134% in the employment-based MarketScan database (21,963 of 16,365,997), with 2019 incidence of 0.19% and 0.07%, respectively. In a sample of 328 records representing 493,006 noninstitutionalized civilian persons with schizophrenia, 87% had Medicaid or Medicare, 15% had private insurance for at least one day during the year, and about 7% were uninsured all year. Schizophrenia is typically diagnosed between the late teens and the early thirties.

In 104 participants who responded to treatment of a first episode, the cumulative first relapse rate five years after initial recovery was 81.9%, and discontinuing antipsychotic therapy increased the risk of an initial relapse by almost five times (hazard ratio 4.89). Across 65 trials with data for 6,493 participants, relapse at one year occurred in 27% of those given antipsychotic drugs and 64% of those given placebo. Across 50 studies, the median proportion meeting recovery criteria was 13.5%; in first-episode psychosis, the pooled rate of remission was 58% (mean follow-up 5.5 years) and the pooled prevalence of recovery was 38% (mean follow-up 7.2 years). Across 135 studies, all-cause mortality in people with schizophrenia was 2.52 times that of control groups. In a cohort of 1,138,853 adults with schizophrenia in United States Medicaid, the all-cause standardized mortality ratio was 3.7, and cardiovascular disease had the highest mortality rate (403.2 per 100,000 person-years). One analysis estimated a weighted average of 14.5 years of potential life lost and a weighted average life expectancy of 64.7 years, and the National Institute of Mental Health reports an estimated average of 28.5 years of potential life lost in the United States. The lifetime risk of suicide is approximately 5%; in a cohort of 668,836 Medicare beneficiaries with schizophrenia, the suicide rate was 74.00 per 100,000 person-years, 4.5 times the rate in the general United States population.

Across 12 studies (11,958 participants), the rate of treatment-resistant schizophrenia was 22.8% among all first-episode cohorts. In one cohort, 13,042 of 29,823 people (43.7%) were rehospitalized during follow-up. The 30-day readmission rate after an initial hospital stay with a principal diagnosis of schizophrenia was 15.7%, and Medicaid index admissions for schizophrenia spectrum and other psychotic disorders had a 30-day readmission rate of 23.7% (39,300 readmissions after 166,100 index admissions). Metabolic syndrome was present in 40.9% of 689 CATIE baseline participants by NCEP criteria, the overall rate in a meta-analysis was 32.5%, and the pooled prevalence of cardiovascular disease in severe mental illness was 9.9% (odds ratio 1.53 against controls). At CATIE baseline, 72.9% of participants reported no employment activity, and 16.9% of United States adults with schizophrenia spectrum disorders were employed, compared with 61.0% of adults without. In time trade-off interviews, 49 participants with stable schizophrenia assigned a mean utility of 0.92 to stable schizophrenia and 0.60 to relapse. In a survey of 200 unpaid caregivers in the United States, care averaged 36.1 hours per week and 79% of caregivers met criteria on the Burden Assessment Scale. The excess economic burden of schizophrenia in the United States in 2019 was estimated at $343.2 billion at a prevalence of 1.19% (3,906,050 people), or $87,856 per person, and at $215.1 billion at a lifetime prevalence of 0.72%. The $343.2 billion comprised excess direct health care costs of $62.3 billion ($15,957 per person), direct non-health care costs of $35.0 billion ($8,956 per person), and indirect costs of $251.9 billion ($64,479 per person; 73.4% of the total), of which caregiving contributed $112.3 billion. In the same analysis, mean total health care costs per patient were $26,904 with commercial insurance, $26,095 with Medicaid, and $34,391 with Medicare. Other claims analyses reported total healthcare costs of $32,920 per patient per year in Medicaid, total annual all-cause costs of $23,662 in Medicare fee-for-service, and a mean cost of $1,806 per patient per month in commercial insurance.