Optimisation of prescription in patients with long-term treatment-resistant schizophrenia

Abstract

Objective: The aim of this clinical review was to investigate the effectiveness and safety of the practice of antipsychotic poly-pharmacy (AP) in the long-term management of hospitalised patients with insufficient response to antipsychotic monotherapy. Method: The databases Medline, PsycINFO, Embase and Scopus were searched. Studies were required to include inpatients with long-term, treatment-resistant schizophrenia on maintenance AP. The search was restricted to systematic review studies. Results: The review yielded four studies of interest that showed no categorical advantage for maintenance AP for the population of interest. However, clozapine combination faired marginally well. Particular weaknesses of the present literature are low number of participants, and inadequate monitoring of potential adverse effects. The evidence on the risks and benefits of maintenance AP is not generally considered adequate to warrant a recommendation for its use in routine clinical practice in psychiatry. Conclusions: This review provides a synthesis of the evidence on the maintenance use of AP for hospitalised patients with long-term, treatment-resistant schizophrenia. The results show both no support for AP with some marginal benefit for clozapine combination therapy, and methodological weaknesses of the included studies. These findings have clinical implications for treatment decisions and suggest that sufficiently powered studies are needed.

Antipsychotic dosing: found in translation

“…Identified dosing guidelines based on this line of approach have translated to clinical practice, and evidence indicating that high doses 98 and antipsychotic polypharmacy 99 are still used is more likely a reflection of the sizable population with TRS. 100 Although not an objective of the early PET work, findings related to the newer antipsychotics, in particular clozapine and quetiapine, in combination with preclinical receptor binding work, challenged the notion that high and sustained D 2 occupancy is required to maintain antipsychotic response. This too had immediate implications for clinical practice, where antipsychotics are routinely administered in multiple daily dosing schedules shaped by their half-life.…”