Objective To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD).
Methods Patients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase.
Results Between January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI −0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline.
Conclusions In this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients.
Trial registration number NTR2478
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Contributors MAJT, JMD and JHTM designed the study. YEMD and JHTM collected data. YEMD, MAJT, JMD, JHTM and RJdH analysed and interpreted data. YEMD wrote the paper and designed the figures and tables. JMG, EZ, DvP, MFC, RZ, BP, AGM and JDS assessed the primary outcome based on video-tapes of the patients. All other authors drafted and critically revised the paper.
Funding This study was funded by Prinses Beatrix fund and Ipsen.
Disclaimer The funders (Prinses Beatrix Fund, Ipsen) were not involved in the study design, data collection, data analysis, data interpretation or writing of the manuscript.
Competing interests YEMD, JHTMK and MAJT report grants from Prinses Beatrix Fund, non-financial support from Ipsen, during the conduct of the study. JHTMK reports grants from Ipsen, grants from Allergan, grants from Merz, outside the submitted work. MAJT reports grants from Gossweiler Foundation, grants from Phelps Stichting, grants from Stichting wetenschapsfonds dystonie vereniging, grants from Fonds NutsOhra, grants from Ipsen, Allergan, Merz, Actelion, grants from SNN Kennisontwikkeling, European funding, grants from Fonds psychische Gezondheid, outside the submitted work. All other authors have nothing to disclose. The authors vouch for the accuracy and completeness of the data and for the fidelity of this report to the study protocol.
Patient consent for publication Not required.
Ethics approval The study protocol was approved by the local medical ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.
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