Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark:A nation-wide pharmacoepidemiological study

Although evidence for efficacy of antipsychotic polypharmacy (APP) is sparse, APP is common in schizophrenia. The national Danish health registers were accessed to examine in schizophrenia patients: (1) cross-sectional prevalences of APP (1996-2012); (2) geographic variations in APP (2012); and (3) correlates of APP (2012). APP increased from 17.2% in 1996 to 30.8% in 2006 (p<0.001), declining to 24.6% in 2012 (p<0.001) (overall trend 1996-2012: α=0.653, 95% confidence interval (CI):0.327-0.979, p<0.001). Comparing the 1996-2005 and 2006-2012 cohorts APP occurred significantly faster in the 2006 cohort after schizophrenia diagnosis (p<0.0001). The predominant APP type changed from first-generation antipsychotic combinations in 1996 (77.3%) to first+second-generation antipsychotic combinations in 2003 (70.3%) and second-generation antipsychotic combinations in 2012 (59.2%). In 2012, the prevalence of APP varied from 19.4% in Copenhagen to 29.3% in the region of Zealand. Independent correlates of APP, explaining 37.9% of the variance, included a higher number of patients per psychiatrist (OR=1.04/10 patients, CI=1.03-1.06, p<0.001),lower proportion of males (OR=0.80, CI=0.74-0.86), younger age (OR=1.00, CI=0.99-1.00), several schizophrenia subtypes (paranoid: OR=1.24, CI=1.11-1.38,hebephrenic: OR=1.30, CI=1.03-1.63, other: OR=1.95 CI=1.17-3.24, unspecified: OR=1.21 CI=1.05-1.40), living alone (OR=1.12, CI=1.01-1.24), being institutionalized (OR=1.23, CI=1.06-1.42), receiving early retirement pension (OR=1.21, CI=1.10-1.34), higher Charlson Co-morbidity Index score (OR=1.13, CI=1.07-1.19), higher antipsychotic defined daily doses (OR=3.05, CI=-2.95-3.16), treatment with clozapine (OR=3.09, 95% CI=2.78-3.44), and treatment with antidepressants (OR=1.97 (CI=1.83-2.13), long-acting injectable antipsychotics (OR=1.48, CI=1.34-1.63), and anticholinergics (OR=1.74, CI=1.51-2.01). APP remains common in schizophrenia with substantial temporal and geographical variation, being associated with indicators of illness severity and chronicity.