Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

The Relationship Between Early Haloperidol Response and Associated Extrapyramidal Side Effects

Rasmussen, Sean A. PhD; Rosebush, Patricia I. MD; Mazurek, Michael F. MD

Journal of Clinical Psychopharmacology: February 2017 - Volume 37 - Issue 1 - p 8–12
doi: 10.1097/JCP.0000000000000637
Original Contributions

Background Early response to antipsychotic medication within 2 weeks of initiating treatment can predict psychiatric outcomes. However, it is unclear whether early response is also predictive of extrapyramidal side effects (EPSs) associated with antipsychotic medications.

Methods In this study, we investigated 136 consecutive antipsychotic-naive, first-episode psychosis patients naturalistically treated with haloperidol. Patients were assessed at baseline and weekly after treatment initiation using the Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. Dystonia, parkinsonism, akathisia, and dyskinesia were also assessed weekly using standardized rating scales. Regression analyses were used to determine whether early response at week 2 of treatment predicted the incidence of EPS at any point during hospitalization. A secondary analysis was conducted to determine whether early response continued to predict EPS in patients who experienced no EPS within the first 2 weeks of treatment.

Results The analyses demonstrated that greater Brief Psychiatric Rating Scale percent improvement at week 2 predicted a decreased risk of EPSs (P = 0.004), even in patients who did not show any EPSs within the first 2 weeks of treatment (P = 0.005). For specific EPS, early response predicted decreased incidences of parkinsonism (P = 0.028) and dyskinesia (P = 0.025), but not akathisia or dystonia. Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale improvement at week 2 did not predict EPSs. In addition, EPSs were not predicted by the maximum antipsychotic dose received during hospitalization.

Conclusions These results indicate that early antipsychotic response is valuable not only for predicting psychiatric outcomes, but also for predicting the risk of EPSs.

From the Departments of *Medicine, †Psychiatry & Behavioural Neurosciences, and ‡Medicine (Neurology), McMaster University, Hamilton, Ontario, Canada.

Received May 2, 2016; accepted after revision November 1, 2016.

Reprints: Sean A. Rasmussen, PhD, McMaster University, St Joseph’s Hospital, Fontbonne Bldg, Rm 416, 301 James St S, Hamilton, Ontario, Canada L8P 3B6 (e-mail:

This work was supported by funding from the Stanley Medical Research Institute and the Ontario Mental Health Foundation.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.