Exposure to psychotropic medications and mortality in schizophrenia: a 5-year national cohort study

Abstract

Background: Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia.

Methods: We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted.

Results: A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07-1.27; HR in moderate dose: 1.32, 95% CI 1.21-1.44; HR in high dose: 1.83, 95% CI 1.67-2.01)].

Conclusions: The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

Keywords: Antidepressant; antipsychotic; daily defined dosage; mood stabilizer; mortality; sedative-hypnotic.

Fig. 1.

HRs and 95% CIs for exposure to antipsychotics, antidepressants, mood stabilizers and sedatives-hypnotics for overall mortality^a. ^a Survival analysis was conducted by Cox regressions with controlled variables including gender, age, socioeconomic status (insurance premium level, low household income and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness certificate, psychiatric ward admission during the first year), and concomitant psychotropic agents use. HR for overall mortality was calculated in different degree of exposure for antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5DDD), moderate exposure (0.5–1.5DDD) and high exposure (>1.5DDD). The scale of vertical axis was adjusted by level of HRs.

Fig. 2.

HRs and 95% CIs for exposure to antipsychotics, antidepressants, mood stabilizers and sedatives-hypnotics for cardiovascular mortality^a. ^a Survival analysis was conducted by Cox regressions with controlled variables including gender, age, socioeconomic status (insurance premium level, low household income and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness certificate, psychiatric ward admission during the first year), and concomitant psychotropic agents use. HR for overall mortality was calculated in different degree of exposure for antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5DDD), moderate exposure (0.5–1.5DDD) and high exposure (>1.5DDD). The scale of vertical axis was adjusted by level of HRs.

Fig. 3.

HRs and 95% CIs for exposure to antipsychotics, antidepressants, mood stabilizers and sedatives-hypnotics for suicide mortality^a. ^a Survival analysis was conducted by Cox regressions with controlled variables including gender, age, socioeconomic status (insurance premium level, low household income and urbanization level), health condition (non-psychiatric health cost), disease severity (catastrophic illness certificate, psychiatric ward admission during the first year), and concomitant psychotropic agents use. HR for overall mortality was calculated in different degree of exposure for antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, which were categorized into four groups with no exposure, low exposure (<0.5DDD), moderate exposure (0.5–1.5DDD) and high exposure (>1.5DDD). The scale of vertical axis was adjusted by level of HRs.