TRADITIONAL PHARMACOLOGICAL TREATMENTS FOR SPASTICITY - PART-2 - GENERAL AND REGIONAL TREATMENTS

Systemic pharmacologic treatments may be indicated in conditions in wh ich the distribution of muscle overactivity is diffuse Antispastic dru gs act in the CNS either by suppression of excitation (glutamate), enh ancement of inhibition (GABA, glycine), or a combination of the two. O nly four drugs are currently approved by the US FDA as antispactic age nts: baclofen, diazepam, dantrolene sodium, and tizanidine. However, t here are a number of other drugs available with proven antispastic act ion. This chapter reviews the pharmacology, physiology of action, dosa ge, and results from controlled clinical trials on side effects. effic acy, and indications for 21 drugs in several categories. Categories re viewed include agents acting through the GABAergic system (baclofen, b enzodiazepines, piracetam, progabide); drugs affecting ion flux (dantr olene sodium, lamotrigine, riluzole); drugs acting on monoamines (tiza nidine, clonidine, thymoxamine, beta blockers, and cyproheptadine); dr ugs acting on excitatory amino acids (orphenadrine citrate); cannabino ids; inhibitory neuromediators; and other miscellaneous agents. The te chnique, advantages, and limitations of intrathecal administration of baclofen, morphine, and midazolam are reviewed. Two consistent limitat ions appear throughout the controlled studies reviewed: the lack of qu antitative and sensitive functional assessment and the lack of compara tive trials between different agents. In the majority of trials in whi ch meaningful functional assessment was included, the study drug faile d to improve function, even though the antispastic action was signific ant. Placebo-controlled trials of virtually ail major centrally acting antispastic agents have shown that sedation, reduction of global perf ormance, and muscle weakness are frequent side effects. It appears pre ferable to use centrally acting drugs such as baclofen, tizanidine, an d diazepam in spasticity of spinal origin (spinal cord injury and mult iple sclerosis), whereas dantrolene sodium, due to its primarily perip heral mechanism of action, may be preferable in spasticity of cerebral origin (stroke and traumatic brain injury) where sensitivity to sedat ing effects is generally higher. intrathecal administration of antispa stic drugs has been used mainly in cases of muscle overactivity occurr ing primarily in the lower limbs in nonambulatory, severely disabled p atients, but new indications may emerge in spasticity of cerebral orig in. Intrathecal therapy is an invasive procedure involving long-term i mplantation oi a foreign device, and the potential disadvantages must be weighed against the level of disability in each patient and the res istance to other forms of antispastic therapy In all forms of treatmen t of muscle overactivity, one must distinguish between two different g oals of therapy: improvement of active function and improvement of hyg iene and comfort. The risk of global performance reduction associated with general or regional administration of antispastic drugs may be mo re acceptable when the primary goal of therapy is hygiene and comfort than when active function is a priority. (C) 1997 John Wiley & Sons, I nc.