Table 4.

Botulinum toxin: randomized, placebo-controlled trials

Study [ref.]	Indication	n	Dose	Primary endpoint	Result
OnabotulinumtoxinA (Ona)
Jankovic and Orman, 1987 [119]	Blepharospasm	11	25 or 50 U/eye vs placebo	Fahn scale	76 % improvement on clinical scale, p < 0.01
				Hyperkinesia Rating Scale	60.7 % improvement on self-assessment, p < 0.01
				Self-assessment	38.9 % improvement on videotape, p < 0.04
				Standardized video
Greene et al., 1990 [120]	Cervical dystonia	55	Varied active dose vs placebo	Columbia Torticollis Rating Scale	Significant improvement in all except one subscore of rating scale
Jankovic and Orman, 1987 [119]	Oromandibular dystonia, cervical dystonia	8	Mean dose 52.8 U vs placebo	Fahn scale	Significant improvement in clinical and videotape score, p < 0.01
				Self-assessment
				Standardized video
Yoshimura et al., 1992 [121]	Limb dystonia	17	13–120 U vs placebo	Subjective assessment	82 % had subjective improvement, p < 0.001
				Video assessment	No significant improvement in objective assessment compared with placebo
Tsui et al., 1993 [122]	Limb dystonia	11	25–30 U/muscle vs placebo	Objective measures of writing	Significant improvement in pen control, p < 0.05
					Significant improvement in speed completion of Gibson’s maze, p < 0.05
Cole et al., 1995 [123]	Limb dystonia	10	5–30 U vs placebo	Subjective patient rating	8 patients had subjective improvement
				Objective testing	6 patients with an objective test that verified the improvement
				Videotape assessment
Troung et al., 1991 [124]	Laryngeal dystonia (adductor)	13	5 U/thyroarytenoid muscle vs placebo	Objective assessments of speech	Significant improvement in speech perturbation, spectrographic analysis, and fundamental frequency range
				Subjective assessment of speech	Phonation time and fundamental frequency unchanged.
					Significant improvement in subjective assessment
AbobotulinumtoxinA (Abo)
Truong et al., 2008 [125]	Blepharospasm	120	40, 80, 120 U/eye vs placebo	Percentage of normal activity BDS at 4 weeks	Percentage of normal activity of BDS significantly better with Abo vs placebo with all doses, p < 0.01
Poewe et al., 1998 [126]	Cervical dystonia	75	250, 500, or 1000 U vs placebo	Modified Tsui scale at weeks 2, 4, and 8	Significant reduction modified Tsui scale in 500 and 1000 U groups at week 4, p < 0.05
Truong et al., 2005 [127]	Cervical dystonia	80	500 U vs placebo	TWSTRS at 4 weeks	Greater mean reduction with Abo vs placebo (9.9 vs 3.8, p ≤ 0.013)
Truong et al., 2010 [128]	Cervical dystonia	116	500 U vs placebo	TWSTRS at 4 weeks	Greater reduction with Abo vs placebo (–15.6 ± 2.0) vs 6.7 ± 2.0), p < 0.001
Lee et al., 2010 [129]	Oromandibular dystonia	12	80 U vs placebo	Number of EMG-recorded bruxism events at 4, 8, and 12 weeks	Significantly decreased bruxism events in the masseter at all time points
Kruisdijk et al., 2007 [130]	Limb dystonia	40	20 U vs placebo	Patient’s choice to continue treatment	70 % in Abo group vs 31.6 % in placebo group, p = 0.03 chose to continue
IncobotulinumtoxinA (Inco)
Jankovic et al., 2011 [131]	Blepharospasm	109	Up to 50 U/eye vs placebo	JRS at 6 weeks	Significant improvement with JRS with Inco vs placebo (–0.83 vs +0.21, p < 0.01)
Comella et al., 2011 [132]	Cervical dystonia	233	120 or 240 U vs placebo	TWSTRS at 4 weeks	Significant improvement with 120 U −9.9, 240 U −10.9 vs placebo −2.2, p < 0.01
RimabotulinumtoxinB (Rima)
Lew et al., 1997 [133]	Cervical dystonia	122	2500, 5000, or 10,000 U vs placebo	TWSTRS at 4 weeks	Significant improvement in all active groups compared to placebo: 2500 U –11.6, 5000 U –12.5, 10,000 U –16.4 vs placebo –3.3, p <0.05
Brashear et al., 1999 [134]	Cervical dystonia	109	5000 or 10,000 U vs placebo	TWSTRS at 4 weeks	Significant reduction with 5000 U 9.3, p = 0.0004 and 10,000 U 11.7, p = 0.0115 vs placebo 4.3
Brin et al., 1999 [135]	Cervical dystonia	77	10,000 U vs placebo	TWSTRS at 4 weeks	Significant improvement with Rima vs placebo (–11.1 vs –2.0, p = 0.0001)

BDS = Blepharospasm Disability Scale; TWSTRS = Toronto Western Spasmodic Torticollis Rating Scale; EMG = electromyography; JRS = Jankovic Rating Scale