Antipsychotic drug prescription sequence analysis in relation to death occurrence and cardiometabolic drug usage: A retrospective longitudinal study

Background and objectives

The potential role of antipsychotics in increasing cardiovascular risk of mortality is still debated. The aim of this study was to assess the death risk associated with sequences of first-generation antipsychotic (FGA) and second-generation antipsychotic (SGA) prescriptions, including clozapine and lithium, and drugs for cardiometabolic diseases.

Methods

We conducted a retrospective longitudinal analysis involving 84,881 patients who received antipsychotics between 2008 and 2012. Data on deaths were collected from the National Death Registry. The sequence creation was performed according to an algorithm that iterates prescriptions in chronological order and appends them to the end of the patient's prescription sequence. Fuzzy set qualitative comparative analysis (FsQCA) was also used to produce causal combinations of conditions that best lead to survival.

Results

There were 1,095,518 antipsychotic prescriptions and 16,010 deaths among antipsychotic users. Among the reimbursement data, 85,272 drug sequences were identified. The most prevalent sequence consisted of FGA (69.1%). Subsequent groups consisted of FGA, followed by SGA (13.1%) and SGA-only (12.3%) sequences. The highest occurrence of death and cardiometabolic drug use after introducing antipsychotic treatment was observed for clozapine. The FsQCA analysis revealed the highest coverage for combinations of young age with FGA (40.6%) or with no cardiometabolic risk factors drug therapy (39.5%).

Conclusion

The sequence analysis suggests that clozapine is associated with an increased death risk compared to FGA and SGA.