Switching antipsychotics to partial dopamine D2-agonists in individuals affected by schizophrenia: a narrative review

Abstract

Objective

The aim of this review is to analyse the literature regarding studies centred on the clinical outcome of individuals affected by schizophrenia and treated with various antipsychotics, and then switched to orally administered partial D2-dopamine agonists (PD2A): Aripiprazole (ARI), brexpiprazole (BREX) or cariprazine (CARI).

Method

A PubMed literature search was performed on 16 February 2021, and updated on Jan 26, 2022 for literature on antipsychotic switching in individuals affected by schizophrenia. Literature was included from 2002 onward. Six strategies were defined: Abrupt, gradual and cross-taper switch, and 3 hybrid strategies. The primary outcome was all-cause discontinuation rate per switch strategy per goal medication.

Results

In 10 reports on switching to ARI, 21 studies with different strategies were described, but there were only 4 reports and 5 strategies on switching to BREX. Only one study about CARI was included, but it was not designed as a switch study. The studies are difficult to compare due to differences in methodology, previous antipsychotic medication, doses of the introduced P2DA and study duration.

Conclusion

This analysis did not reveal evidence for a preferable switching strategy. A protocol should be developed which defines optimal duration, instruments to be used, and the timing of the exams.

KEY MESSAGES

• Most switch studies on partial D2-agonists focus on ARI, with only a few on BREX, while little is known about the clinical outcome of switching individuals to CARI

• There is a wide variation of possible switch methods: Abrupt switch – gradual switch – cross-tapering switch – hybrid strategies including plateau switch

• The protocols used differ considerably between the studies. A strict comparison between the studies is difficult, for which reason the present evidence does not support an unambiguous preference for a particular switch strategy.

• From a methodological point of view, a standardised clinical protocol should be developed to allow comparisons between studies regarding the clinical outcome of individuals switched from one antipsychotic drug to another

Keywords:

• Partial D2-dopamine receptor agonists
• antipsychotics
• aripiprazole
• brexpiprazole
• cariprazine
• switch
• schizophrenia spectrum disease

Acknowledgements

The first draft of this review was written by P. Baumann and P. Bauknecht. All authors reviewed and edited successive versions of the manuscript, and all authors read and approved of the final version.

Disclosure statement

Pierre Baumann has received honoraria from Janssen/Switzerland and Lundbeck/Switzerland. Philipp Bauknecht is an employee of Dr. Carl GmbH, Stuttgart, Germany. Dr. Kuzin received travel grants from Sunovion Pharmaceutical (Basel, Switzerland) and Otsuka Pharmaceutical (Glattbrugg, Switzerland). He also received a travel grant, participated, and obtained a grant at speaker board of Lundbeck (Zurich, Switzerland). Georgios Schoretsanitis has served as a consultant for HLS Therapeutics and Thermo Fisher and has received speaker fees from HLS Therapeutics.

Additional information

Funding

Medical writing services and implementation of the original literature search were provided by Dr. Carl GmbH, Stuttgart, Germany, and financially supported by Lundbeck (Schweiz) AG and Otsuka Pharmaceutical (Switzerland) GmbH.