Brans 1996 a

Methods	Randomised, multicenter, double‐blind, 2 arms, parallel study.Method of randomisation: computer program.Data analysed on an intention‐to‐treat basis for all patients that receive any study medication.Location: 4 centers in Netherlands.Duration: 12 weeks.
Participants	66 participants were enrolled.Trihexyphenidyl arm: 33 participants (1 withdrawal prior to receive study medication: 3%); 24 participants were female and 9 were male, mean age was 51.2 ± 12 (sd) years; ethnicity: not stated; mean duration of illness: 8.6 ± 6,8 (sd) years; 21 participants with course of disease of at least 5 years; 21 participants with a history of progressive disease; mean TWSTRS‐Disability score at baseline: 15.8 ± 5.2 (sd); mean Tsui score at baseline: 14 ± 4.3 (sd), mean General Health Perception Subscale score at baseline: 67.3 ± 10.5 (sd).BoNT/A arm: 33 participants (1 withdrawal prior to receive study medication: 3%); 16 participants were female and 17 were male; mean age was 50.1 ± 11.9 (sd) years; ethnicity: not stated; mean duration of illness: 10.1 ±1 0.3 (sd) years; 23 participants with course of disease of at least 5 years; 9 participants with a history of progressive disease; mean TWSTRS‐Disability score at baseline: 15.9 ± 5.4 (sd); mean Tsui score at baseline: 15.3 ± 4.3 (sd), mean General Health Perception Subscale score at baseline: 67.5 ± 10.8 (sd).Inclusion criteria: Idiopathic, mainly focal, Cervical Dystonia (CD) for at least 1 year; Informed consent.Exclusion criteria: age under 18 years; pregnancy; multifocal or generalized dystonia; other neurological disease, coagulation disorders, secondary dystonia; and previous treatment with BoNT/A.
Interventions	The study drug Trihexyphenidyl (and equivalent placebo) was administered in tablets of 2 mg. The initial dose was one‐half tablet daily, increased every 3 days to a maximum of 3 tablets four times daily (24 mg daily).The study drug BoNT/A (Dysport®) was diluted to 20U per 0,1mL of 0.9% sterile saline, and injected under EMG guidance. The selection of muscles to inject, the number of injection sites per muscle, and the volume per injection site were based on the investigator criteria. Participants were injected at baseline (mean dose 292U: range, 38 to 440) and at week 8 (mean dose 262: range, 36 to 440).
Outcomes	The primary efficacy outcome was the difference between the two treatment groups with regard to the change on the TWRTRS‐Disability score. Secondary efficacy outcomes included: difference between the numbers of participants who had an improvement of at least three points on the TWRTRS‐Disability score, difference between changes on the Tsui Scale, difference between the numbers of participants who had an improvement of at least three points on the Tsui Scale, difference between changes on the TWRTRS‐Pain, and difference between changes on the General Health Perception Subscale of the Dutch MOS‐Quality of Life Scale (100‐point scale, with 100 assigned as the best possible score).For all outcomes data were collected at treatment visit (Week 0), and at week 12 (termination).Adverse events data were collected through spontaneously report.
Notes	In one center 5 participants receive half of BoNT/A dose due to an error in dilution.Reasons for withdrawal: 2 participants discontinued the study, one in each group, before receiving the study medication, because of a colon carcinoma and withdrawal of cooperation.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate