Mortality and use of psychotropic medication in sleep apnoea patients: a population-wide register-based study

Abstract

Background: This study aimed to evaluate all-cause mortality in relation to the use of benzodiazepines, antidepressants and antipsychotics in obstructive sleep apnoea (OSA) patients and matched controls.

Methods: Patients with a diagnosis of OSA and no pre-index use of psychotropic medication (n = 38,735) were compared with control subjects (n = 75,941) matched by age, gender, marital status and community location. National register data were used to obtain information on diagnoses (the Danish National Patient Registry), mortality (the Central Person Register) and psychotropic medication use (the Danish Register on Medicinal Product Statistics).

Results: All-cause mortality was higher in patients with OSA than in control subjects. Mortality hazard ratios were higher for OSA patients and controls who were prescribed serotonergic antidepressant drugs (HR = 1.808, SD = 0.015, p = 0.001 in OSA patients; HR = 2.607, SD = 0.158, p < 0.001 in controls), tricyclic antidepressants (HR = 1.846, SD = 0.166, p < 0.001; HR = 2.087, SD = 0.172, p < 0.001), benzodiazepines (HR = 2.590, SD = 0.040, p < 0.001); (HR = 3.705, SD = 0.085, p < 0.001), benzodiazepine-like drugs (HR = 1.980, SD = 0.087, p < 0.001; HR = 2.227, SD = 0.083, p < 0.001), first-generation antipsychotics (HR = 2.894, SD = 0.268, p < 0.001; HR = 1.210, SD = 0.509, NS), and second-generation antipsychotics (HR = 2.069, SD = 0.182, p < 0.001; HR = 1.355, SD = 0.171, NS), compared with those who did not receive the drugs. Interaction analysis suggested that similar or slightly lower mortality was associated with selective serotonin re-uptake inhibitors, benzodiazepines and second-generation antipsychotics in OSA compared with controls when comorbidities were taken into consideration.

Conclusion: All-cause mortality was higher in OSA patients and especially controls treated with benzodiazepines, antidepressants or antipsychotics than in untreated controls. The findings were not controlled for psychiatric comorbidity and the results may have partly been attributable to confounding by indication. The results raised the possibility that the use of psychotropic medication may have deleterious health consequences, but the risk did not seem to be higher in OSA than in controls.

Keywords: All-cause mortality; Antidepressants; Antipsychotics; Benzodiazepines; Hypnotics; Obstructive sleep apnoea (OSA).