Cervical dystonia is the most common form of focal dystonia and is the most studied neurological condition in patients receiving botulinum toxin. In clinical trials of botulinum toxin, there is a placebo response, but this has not been studied systematically.
A systematic review and meta-analysis were conducted to assess and compare the peak and duration of placebo response in people with cervical dystonia receiving botulinum toxin in randomized, blinded controlled clinical trials.
Three databases (Embase, PubMed, Scopus) and two trial registers (Cochrane CENTRAL and Cochrane Movement Disorders Trials Register) were searched by a biomedical librarian in May 2022 and September 2023. Covidence was used for screening titles and abstracts and full text. Two authors independently screened each record and collected data from the included articles. Microsoft Excel was used for data collection. The Cochrane Collaboration’s Risk of Bias tool in randomized trials was used by two authors for each included study. A third author resolved conflicts during screening and discrepancies during data collection and risk of bias assessment. We conducted a random-effects meta-analysis of the mean reduction in the TWSTRS total score at 4 weeks post injection, to assess the clinical change in the placebo arm overall and by TWSTRS pain, severity, and disability scales.
Twelve studies, with moderate overall risk of bias, that included 2,145 participants with 580 randomized to placebo, were included in the systematic review. Clinical changes in the placebo arm were mild with a mean reduction of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score of 3.5 [95% confidence interval (CI): 2.6–4.4] 4 weeks post injection. TWSTRS pain score at week four was 0.9 (95% CI: 0.6 - 1.1; I2 = 59%). TWSTRS severity score at week four was 1.7 (95% CI: 1.3–2.0; I2 = 63%). TWSTRS disability score at week four was 0.7 (95% CI: 0.3–1.0; I2 = 63%). Duration of benefit ranged from 45.1 to 76.3 days with a mean duration of 57.6 days. Dropouts in patients randomized to placebo were due to lack of efficacy, pain, neck weakness, fatigue, and tiredness.
This information on placebo response will be useful in estimating sample size and interpreting participant benefit in future interventional studies of cervical dystonia.