Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study

Abstract

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

Keywords: antidepressant; antipsychotic; daily defined dosage; mood stabilizer; mortality; old-age; polypharmacy; schizophrenia; sedative-hypnotic.

Figure 1

Percentage of each defined daily dose (DDD) dosage exposure of antipsychotics, antidepressants, mood stabilizers, and sedatives/hypnotics.

Figure 2

(a). Hazard ratios and 95% Confidence Intervals for the different exposures to antipsychotics and antidepressants for overall mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for antipsychotics and antidepressants, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios. (b). Hazard ratios and 95% Confidence Intervals for the different exposures to mood stabilizers and sedatives/hypnotics for overall mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for mood stabilizers and sedatives/hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios.

Figure 2

(a). Hazard ratios and 95% Confidence Intervals for the different exposures to antipsychotics and antidepressants for overall mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for antipsychotics and antidepressants, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios. (b). Hazard ratios and 95% Confidence Intervals for the different exposures to mood stabilizers and sedatives/hypnotics for overall mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for mood stabilizers and sedatives/hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios.

Figure 3

(a). Hazard ratios and 95% Confidence Intervals for the different exposures to antipsychotics and antidepressants for CVD mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for antipsychotics and antidepressants, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios. (b). Hazard ratios and 95% Confidence Intervals for the different exposures to mood stabilizers and sedatives/hypnotics for CVD mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for mood stabilizers and sedatives/hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios.

Figure 3

(a). Hazard ratios and 95% Confidence Intervals for the different exposures to antipsychotics and antidepressants for CVD mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for antipsychotics and antidepressants, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios. (b). Hazard ratios and 95% Confidence Intervals for the different exposures to mood stabilizers and sedatives/hypnotics for CVD mortality. Survival analysis utilized Cox regressions and controlled for multiple variables: gender, age, socioeconomic status (insurance level, household income, and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness card, psychiatric ward admission during the first year, and psychiatric-care-related cost), and concomitant psychotropic agent use. The hazard ratio for overall mortality was calculated across varying degrees of exposure for mood stabilizers and sedatives/hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5 DDD), moderate exposure (0.5–1.5 DDD), and high exposure (>1.5 DDD). The scale of the vertical axis was adjusted by the level of the hazard ratios.

Figure 4

Flow chart of the study design. OAS, old-age individuals with schizophrenia.