Pharmacology of Spasticity Medications
1. Overview and Description
- Spasticity definition:
- Spasticity is defined as “a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (‘muscle tone’) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex”.1,2 Spasticity is the result of an upper motor neuron defect and can be the result of spinal cord injury, traumatic brain injury, hydrocephalus, brain infarction, metabolic diseases, or neurodegenerative diseases. Due to its wide range of etiologies, spasticity often manifests as a complex set of problems, which can lead to profound disability. The management of spasticity remains a clinical challenge, so it is essential for physicians to begin to establish clear objectives in their treatment plans. This article will explore the various pharmacologic treatments to spasticity.
- Pharmacokinetics (PK) and Pharmacodynamics (PD)
- In order to discuss the pharmacology of spasticity medications, it is important to understand the concepts of pharmacokinetics and pharmacodynamics. Pharmacokinetics, simply put, is the effect the body has on the drug. It relates to absorption of the drug into systemic circulation, distribution of the drug in tissues, and elimination of the drug via metabolization or excretion. Whereas pharmacodynamics is the effect the drug has on the body. It encompasses the pharmacologic effect of the drug in relation to the clinical response (ex: toxicity vs. effectiveness).
- In order to achieve the desired clinical response, the pharmacokinetic parameters must be overcome to achieve a concentration at the target site. If a dose is not sufficient to provide enough exposure, theoretically less desired clinical response will occur. Understanding the PK of a medication allows providers to anticipate what level of clinical response is anticipated to occur. Titration of medications to a therapeutic window, defined as the range of doses producing a clinical response without causing an adverse event, is the primary goal of medication prescribing. By reaching the therapeutic window, the safest, most judicious practices are employed. Furthermore, if a provider desires a certain clinical response, he or she needs to be aware of what level of exposure is needed in a certain physiologic compartment to obtain this response. The adjustment in dosing allows this exposure to change depending on the prescribing provider’s preferences.
2. Relevance to Clinical Practice
- It is essential to understand the pharmacotherapy of medications used to treat spasticity to improve the quality of life of those affected by the disorder. Medical complications of chronic spasticity include bone deformity, remodeling of soft tissue, and muscle contractures that limit range of motion and eventual postural and functional abnormalities. Ultimately, left untreated, spasticity affects individuals by limiting their independence and ability to perform activities of daily living. The goal of treatment is to decrease abnormal tone and thereby improve function.1
- Due to lack of standardization of assessment and quantification of the degree of spasticity, there is much interpretation left to the individual provider for appropriate treatment. There are no universal guidelines for stepwise management, therefore, it is recommended to incorporate physical and self-management before and while using pharmacologic or procedural medical interventions. See table 1 for available pharmacologic agents.
- It is also important to note that there are no validated prognostic models of spasticity.
- A complete review of medications frequently used for spasticity management is included (Table 1).
3. Cutting Edge/Unique Concepts/Emerging Issues
The emerging concept of utilizing pharmacogenomic data to help predict which patients may respond or may not respond to specific agents has the potential to tailor spasticity treatments towards individuals and ultimately avoiding hypothesis motivated medicine. With time, this personalized medicine may improve patient quality of life, clinical outcomes, and reduce costs. The ultimate goal by modifying pharmacology to the genetic make-up of patients is to eventually shift from the idea of treating the disease in a population based way to treating the patient in an individualized manner.3 By using pharmacogenomic, proteomic, and environmental characteristics, medication regimens can be uniquely tailored to each individual.3
4. Gaps in Knowledge/Evidence Base
- While there are several medications available for the treatment of spasticity, there is still variability in drug responses among individuals. Simultaneously, there are limited studies that objectively evaluate the functional changes among patients who receive treatment. With more research, perhaps in the future, physicians will be able to individualize treatment according to each patient given their response.
- Moreover, a major limitation of spasticity medications is that many are not approved by the US Food and Drug Administration (FDA) for the adult or pediatric populations, and are consequently used as “off-label” medications. Without the FDA approval, dose standardization for medications that are used so widely and frequently remains challenging. An observational study conducted at an inpatient children’s’ rehabilitation center showed that 88% of pediatric patients were prescribed off-label medications at rehabilitation centers, and of that percentage, the majority included central nervous system agents, many of which are described above.4 More research needs to be done on prescribing amongst children in order to optimize treatment in this patient population.
- DiTommaso C, Bell K. Spasticity. 2013; http://me.aapmr.org/kn/article.html?id=38. Accessed 3/14/2017.
- Katz RT. Management of spasticity. American journal of physical medicine & rehabilitation. Jun 1988;67(3):108-116.
- Miller A, Avidan N, Tzunz-Henig N, et al. Translation towards personalized medicine in Multiple Sclerosis. Journal of the neurological sciences. Nov 15 2008;274(1-2):68-75.
- Luedtke KE, Buck ML. Evaluation of Off-label Prescribing at a Children’s Rehabilitation Center. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG. Oct-Dec 2014;19(4):296-301.
Suzan Lisenby, BS
Nothing to Disclose
Sumita Sharma, BS
Nothing to Disclose