Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review

Abstract

Spasticity is a common disabling feature of multiple sderosis. A variety of drugs are in regular use as oral treatment induding badofen, dantrolene, tizanidine, and diazepam. Published evidence of effectiveness is limited. Most trials are of small size, of short duration, and have not reported on functional outcomes. Studies have been published which suggest that badofen, tizanidine, and diazepam are all effective in reducing dinical measures of spasticity, but there is little evidence that they lead to an improvement in patient function. There is no evidence to suggest any difference in effectiveness between them. The evidence that dantrolene has any effect on spasticity is of poor quality. Diazepam and dantrolene are associated with more side effects than baclofen and tizanidine. There is evidence for the effectiveness of gabapentin in reducing spasticity and improving function in the short term, though longer-term studies are needed to establish its true value. One randomized controlled trial of threonine does not support its effectiveness.

Symptomatic Treatment of Multiple Sclerosis

“…For tizanidine (2–24 mg/day p.o., class I evidence [17], [18]) and baclo- fen 10–120 mg/day p.o., class II evidence [19,20,21]), sufficient evidence is available to support their use, whereas dantrolene and tolperisone were not tested appropriately and therefore are used as second-line drugs. Patients undergoing antispastic treatment with these drugs often report reduced spasticity and spasticity-related pain or clonus, especially at night [22]. …”

Historical overview of the rationale for the pharmacological use of prolonged-release fampridine in multiple sclerosis

“…Spasticity, for example, is a common symptom of MS and may affect walking ability. This symptom is usually addressed with oral baclofen or tizanidine [22], although there are no conclusive data of the functional effects of these treatments in patients with MS [23]. More recently, nabiximols has been used as an add-on therapy for those refractory to conventional antispasticity treatment [24].…”

“…Any AE, n (%) 58 (81) 191 (84) 79 (66) 103 (86) Mild AEs, n (%) 16 (22) 59 (26) 36 (30) 39 (33) Moderate AEs, n (%) 35 (49) 98 (43) 36 (30) 53 (44) Severe AEs, n (%) 7 (10) 34 (15) 7 (6) 11 (9) Serious AEs, n (%) 0 (0) 16 (7) 3 (3) 5 (4) Possibly or probably treatment-related AEs, n (%)…”

Cannabinoids in the management of spasticity associated with multiple sclerosis

“…Dantrolene and tolperisone are rarely prescribed. Benzodiazepines offer suffi cient antispastic effect, but are second-line drugs owing to their higher risk of side-effects such as sedation and dependence (Paisley et al 2002;Shakespeare et al 2003). Gabapentin was shown to be effective in treating phasic spasticity (Mueller et al 1997;Cutter et al 2000).…”