5. Tiihonen J, Taipale H, Mehtälä J, et al. Association of antipsychotic polypharmacy vs monotherapy with psychiatric rehospitalization among adults with schizophrenia. JAMA Psychiatry. 2019;76(5):499-507.
In clinical practice, the use of multiple antipsychotic agents for the maintenance treatment of schizophrenia is common but generally not recommended. The effectiveness of antipsychotic polypharmacy in preventing relapse of schizophrenia has not been established, and whether specific antipsychotic combinations are superior to monotherapies for maintenance treatment of schizophrenia is unknown. Tiihonen et al6 investigated the association of specific antipsychotic combinations with psychiatric rehospitalization, which was used as a marker for relapse.
Study design
- This study included 62,250 patients with schizophrenia, treated between January 1, 1996 and December 31, 2015, in a comprehensive, nationwide cohort in Finland. Overall, 31,257 individuals (50.2%) were men, and the median age was 45.6 (interquartile range, 34.6 to 57.9).
- Patients were receiving 29 different antipsychotic monotherapy or polypharmacy regimens.
- Researchers analyzed data from April 24 to June 15, 2018 using psychiatric rehospitalization as a marker for relapse. To minimize selection bias, rehospitalization risks were investigated using within-individual analyses.
- The main outcome was the hazard ratio (HR) for psychiatric rehospitalization during use of polypharmacy vs monotherapy by the same patient.
Outcomes
- Clozapine plus aripiprazole was associated with the lowest risk of psychiatric rehospitalization, with a difference of 14% (HR, .86; CI, .79 to .94) compared with clozapine monotherapy in the analysis that included all polypharmacy periods, and 18% (HR, .82; CI, .75 to .89) in the conservatively defined polypharmacy analysis that excluded periods <90 days.
- Among patients experiencing their first episode of schizophrenia, the differences between clozapine plus aripiprazole vs clozapine monotherapy were greater, with a difference of 22% in the analysis that included all polypharmacy periods, and 23% in the conservatively defined polypharmacy analysis.
- At the aggregate level, any antipsychotic polypharmacy was associated with a 7% to 13% lower risk of psychiatric rehospitalization compared with any monotherapy.
- Clozapine was the only monotherapy among the 10 best treatments.
- Results on all-cause and somatic hospitalization, mortality, and other sensitivity analyses were in line with the primary outcomes.
Conclusion
- This study suggests that certain types of antipsychotic polypharmacy may reduce the risk of rehospitalization in patients with schizophrenia. Current treatment guidelines state that clinicians should prefer antipsychotic monotherapy and avoid polypharmacy. Tiihonen et al6 raise the question whether current treatment guidelines should continue to discourage antipsychotic polypharmacy in the maintenance treatment of schizophrenia.
- Despite the large administrative databases and sophisticated statistical methods used in this study, this approach has important limitations. As Goff10 points out, despite efforts to minimize bias, these results should be considered preliminary until confirmed by RCTs.
6. Stroup TS, Gerhard T, Crystal S, et al. Comparative effectiveness of adjunctive psychotropic medications in patients with schizophrenia. JAMA Psychiatry. 2019;76(5):508-515.
In routine clinical practice, patients with schizophrenia are often treated with combinations of antipsychotics and other psychotropic medications. However, there is little evidence about the comparative effectiveness of these adjunctive treatment strategies. Stroup et al7 investigated the comparative real-world effectiveness of adjunctive psychotropic treatments for patients with schizophrenia.
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