Antipsychotic Polypharmacy in Time Course: Evidence for a Cross-titration Trap

Antipsychotic polypharmacy (APP) is controversial yet applied in 20% of patients with psychotic disorders. We investigated indications for initiating and continuing APP, including the contribution of unfinished cross-titrations.

This 2-month study was part of a prospective study to reduce inappropriate APP in inpatients. With each new prescription resulting in APP, we asked the prescriber for the indication (eg, switching antipsychotics, sedation for agitation/sleep disorders, treatment refractoriness, other) and repeated this at 30 and 60 days. Secondary outcome was unfinished cross-titration at 60 days.

In a consecutive cohort of 55 patients, 80% diagnosed with schizophrenia, switching antipsychotics was the primary initial indication for APP in 31 of 55 patients (56%), followed by sedation in 12 of 55 patients (22%), and treatment refractoriness in 10 of 55 patients (18%). Overall, APP was discontinued after 30 days in 25 of 55 patients (45%) and after 60 days in 28 of 55 patients (51%). At 60 days, APP initiated for switching antipsychotics was ongoing in 9 of 31 patients (29%), APP initiated for sedation was ongoing in 8 of 12 patients (66%), and APP initiated for refractoriness was ongoing in 9 of 10 patients (90%). The initial indication for APP was maintained at 60 days in 21 of 27 patients (78%). Unfinished cross-titration occurred in 9 of 31 patients (29%) with APP initiated for switching antipsychotics.

APP was initiated primarily because of cross-titration switching of antipsychotics. The reason for APP was generally maintained consistently over time, particularly when initiated for treatment refractoriness. Of all patients with APP initiated to switch antipsychotics, 29% ended in unfinished cross-titration.