Efficacy of low-dose D₂/D₃ partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study

Abstract

Objective

Some lines of evidence show that D₂/D₃ receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375–0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability.

Methods

Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit.

Results

SAS total scores decreased significantly during the study in patients with DIP (P<0.001), and mild AEs were detected. Treatments with pramipexole did not show an anti-akathisia effect during the study, while 2 subjects experienced deterioration of akathisia and mood symptoms. The psychiatric symptoms of schizophrenia showed a trend of improvement during the study, but there was no improvement in depressive mood.

Conclusion

A low dose of pramipexole can significantly relieve antipsychotic-induced parkinsonism, but not akathisia. Improvements in psychiatric symptoms of schizophrenia were found, but the results of this study need to be validated in a larger sample. No improvement of mood disorder was detected.

Keywords:

• extrapyramidal symptoms
• antipsychotics
• pramipexole
• clinical trial

Acknowledgments

The authors thank the staff of Drug Clinical Trial Institution of Shanghai Mental Health Center and Dr Lu WH, Dr ZLP, Dr SY, and Dr CY for their contribution to the recruitment of subjects and valuable suggestions. This study is supported by Shanghai Collaborative Innovation Center for Translational Medicine and National Science (Grant No. TM201624), Technology Major Project for Investigational New Drug (Grant No. 2018ZX09734-005), Multi-center Clinical Study of Shanghai Jiao Tong University School of Medicine (Grant No. DLY201620) and Shanghai Committee of Science and Technology Research Project (Grant No. 17411970300).

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.