Persistence with polypharmacy and excessive dosing in patients with schizophrenia treated in four European countries

Abstract

The purpose of this study was to calculate the proportion of patients with schizophrenia receiving persistent antipsychotic polypharmacy and excessive dosing in four European countries; to test the hypothesis that excessive dosing and/or antipsychotic polypharmacy is associated with higher levels of psychopathology; and to establish whether use of second-generation antipsychotics is a protective or a risk factor for polypharmacy and excessive dosing. Participants with schizophrenia were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (Netherlands), and Leipzig (Germany). We defined patients persistently receiving high antipsychotic dose (i.e. excessive dosing) as those with a prescribed daily dose/defined daily dose ratio of >1.5 both at initial assessment and after 1 year of follow-up. Similarly, we defined patients persistently receiving polypharmacy as those being prescribed two or more antipsychotic drugs both at baseline and at follow-up. A sample of 375 participants with schizophrenia was analyzed. A proportion of 28% of patients persistently received high-dose antipsychotic drugs, and a proportion of 13% of patients persistently received antipsychotic polypharmacy. In the multivariate analysis, psychopathology was not a predictor of persistent polypharmacy and excessive dosing; similarly, use of second-generation antipsychotics was not associated with polypharmacy and excessive dosing; however, persistence with high antipsychotic doses was predicted by baseline use of first-generation antipsychotics and second-generation antipsychotics concurrently. Antipsychotic drug use for patients with schizophrenia is only sometimes satisfactory and offers the opportunity of improvement. Clinicians should consider that dose reduction strategies have been shown to be a feasible intervention in patients with schizophrenia.

Polypharmacy and high-dose antipsychotics at the time of discharge from acute psychiatric wards

“…Internationally, the rate of polypharmacy in discharged individuals was 28% in Italy, 10 27.5% in Canada, 15 35.6% in Norway 16 and 40% in the Medicaid group in the USA, 17 all higher than what we observed. However, our finding was similar to that of Centorrino et al 18 in the USA and Barbui et al 12 in Italy where 15.8 and 13% respectively were on polypharmacy.…”

“…11 Studies based on patients in the community also report higher rates. A study involving four European countries observed that 28% persistently received highdose antipsychotics, 12 whereas Tungaraza et al 13 observed that 14% of their UK-based study group were similarly treated.…”

Prevalence of and factors associated with antipsychotic polypharmacy in patients with serious mental illness: Findings from a cross-sectional study in an upper-middle-income country

“…29 In keeping with previous studies, the PDD:DDD ratio for APP was calculated as the sum of the individual PDD:DDD ratios of all antipsychotics prescribed to a patient; high-dose prescribing was defined as a PDD:DDD of greater than 1.5. [30][31][32] In addition to antipsychotic agents, data on coprescription of anticholinergic agents, mood stabilizers, antidepressants, and benzodiazepines were captured.…”

Frontale Hirnvolumenminderung durch Antipsychotika?

“…Ho et al [38] empfehlen nach der aktuellen Studienlage, Antipsychotika nicht abzusetzen, jedoch "jedem Patienten die niedrigste Dosis (zu) verordnen, um Symptome zu kontrollieren" -und zwar bereits bei Therapiebeginn. Dies steht in Gegensatz zum auch heute noch teilweise praktizierten Vorgehen mit vergleichsweise hohen Einstiegsdosierungen, weiteren Dosissteigerungen [109] und nicht evidenzbasierter Polypharmazie im Verlauf [110,111]. Ein abnehmendes Ansprechen durch dosisabhängige Vermehrung ("upregulation"), Sensibilisierung und vermehrte Dopaminsynthese und Ausschüttung der mesolimbisch-striatalen D2-Rezeptoren kann u. a. dafür ursächlich sein [112,113].…”