Prescribing for common complications of spinal cord injury

Case description

You are seeing one of your regular patients, Devon, who was involved in a motor vehicle collision 2 years ago and has complete T8 SCI. During his appointment you identify 3 problems interfering with function:

• He has burning pain in all areas below the level of his injury that is interfering with sleep.

• In the past year he has contacted your office on 6 occasions reporting a temperature above 37.6°C and cloudy, sometimes bloody urine. Cultures you have ordered have consistently grown 1 primary organism.

• Over the past 9 months Devon has found his spasticity has increased and is occasionally making it difficult for him to transfer into the car to get to work.

Sources of information

This review is based on the results of 2 studies by the authors. The first is a nationwide survey of prescription medication use among people with SCI in Canada.¹ The survey was distributed with the assistance of 3 national community-based consumer advocacy and research organizations: the Rick Hansen Foundation, Spinal Cord Injury Canada, and the Canadian Spinal Research Organization. Of the 108 survey participants, 59 were male (55%); 87 individuals had traumatic SCI (80%); and 57 had paraplegia (53%) while 51 had tetraplegia (47%). The mean (SD) age of the participants was 48 (14) years, and the mean (SD) time since injury was 20 (12) years. The survey asked participants about their medication use (number and names of prescribed medications), demographic characteristics, and injury details.² The study was approved by the Health Sciences Research Ethics Board at Queen’s University in Kingston, Ont.

The second study contributing to this review is a longitudinal study of secondary complications associated with SCI, resulting in an innovative knowledge translation tool called Actionable Nuggets.^3,4 Actionable Nuggets is a mobile app designed specifically for family physicians, offering brief, actionable, evidence-based information on the top 20 health concerns associated with SCI.⁵

Main message

Three complications that required pharmacologic treatment among individuals with SCI were pain (treated in 57% of our sample), muscle spasms (54%), and recurrent urinary tract infections (UTIs, 43%).

Pain. As many as 8 types of pain are commonly associated with SCI, but by far the most prevalent and impactful is neuropathic pain, which is estimated to affect 75% of patients.⁶ A 4-item screening tool, the Spinal Cord Injury Pain Instrument, is recommended for distinguishing neuropathic from non-neuropathic pain. At a cut-off score of 2 out of 4 (50%), the Spinal Cord Injury Pain Instrument has sensitivity of 78%, specificity of 73%, and diagnostic accuracy of 76%.⁷

First-line agents for the treatment of chronic neuropathic pain in SCI according to the latest evidence are pregabalin, gabapentin, and amitriptyline,^8,9 making up 51% of prescriptions issued for pain in our sample.

Tricyclic antidepressants (TCAs) are as effective as gabapentinoids for relief of neuropathic pain with SCI, but they may be poorly tolerated by some patients with SCI because of their anticholinergic side effects and their effect on cardiac conduction.⁸ Typically, the TCA dose required to achieve adequate pain relief in patients with SCI is below the threshold for anticholinergic side effects that would exclude their use.⁸ Tricyclic antidepressants are contraindicated for patients with glaucoma, symptomatic prostatism, and substantial cardiovascular disease.¹⁰

Of the TCAs (amitriptyline, nortriptyline, desipramine), amitriptyline is most commonly prescribed to patients with SCI because of its efficacy in relieving neuropathic pain.¹¹ It is more likely than other TCAs to produce drowsiness,⁸ but this soporific effect can be quite useful, especially when neuropathic pain disrupts sleep. Amitriptyline had been prescribed to less than 10% of our sample population, perhaps suggesting underuse.

Second-line agents for the treatment of neuropathic pain in SCI are tramadol and lamotrigine.⁹ There is mixed evidence for third- and fourth-line agents, such as cannabinoids, botulinum toxin, and baclofen.⁸ There is no evidence in favour of clonidine (alone), mexiletine, levetiracetam, valproic acid, trazodone, or duloxetine.^8,9 In our sample, approximately one-third of patients had been treated with second- or third-line agents.

Opioids had been prescribed for pain in 32% of our sample. While opioids have an important place in the treatment of pain, caution must be exercised due to increased risk of falls and reduced mobility.¹² Concerns about opioid dependence and addiction can be addressed using clinical guidelines¹³ and other resources such as the Opioid Manager tool from McMaster University in Hamilton, Ont.¹⁴

Prescription for SCI-related pain is complex, especially given altered pharmacokinetics and multiple sources of pain (eg, neuropathic, degenerative, arthritic, inflammatory [acute and chronic], or visceral).^15,16 Multiple medications may be required depending on the nature or source of the pain. Pain medication regimens need to be individualized according to source of pain and response to treatment.

Muscle spasms. As many as three-quarters of people with SCI experience spasticity, particularly those with lesions above T5.¹⁷ Uncontrolled spasticity can be a major obstacle to community integration, transportation, functional mobility, and personal and intimate relationships. Fifty-four percent of participants in our study had been treated for muscle spasms. The first-line pharmacologic management of spasms is oral or intrathecal baclofen,¹⁸ prescribed to 80% of those treated for muscle spasms in our sample. Other antispasmodic medications include cannabis, clonidine, cyproheptadine, dantrolene, diazepam, gabapentin, l-threonine, 4-aminopyridine, and tizanidine—all of which were used by less than 10% of individuals in our sample.

We were surprised to discover the extent to which short-acting benzodiazepines had been prescribed to treat spasticity. While these may be used short-term for intermittent problems with spasticity, they are not part of the recommended treatment paradigm because of their negative effects on individuals’ ability to void and ambulate.^10,18,19

It should be noted that spasticity is often related to an underlying problem, such as a UTI or pain, thus treatment of concomitant conditions may also result in decreased spasticity.

Recurrent UTIs. Recurrent UTIs (>3 per year) are a major health concern among individuals with neurogenic bladder. They are often polymicrobial, antibiotic resistant, and caused by a wider variety of pathogens than are UTIs in the general population. Definitive diagnosis of UTI in patients with SCI requires 3 conditions: explicit signs and symptoms, substantial bacteriuria, and pyuria (≥50 white blood cells per high-power field).^20,21

The most common medications prescribed to our survey respondents for UTIs were nitrofurantoins, making up 24% of the prescriptions issued for this condition, followed by cephalosporins (especially cephalexin; 20%). Other categories of drugs used to treat UTIs included fluoroquinolones (especially ciprofloxacin; 15%), β-lactams (eg, amoxicillin; 7%), trimethoprim-sulfamethoxazole (7%), and tetracyclines (7%).

There is no superior class of antibiotics, nor is there an evidence-based standard of care for antimicrobial treatment of UTI in patients with SCI. Guidelines for selecting antimicrobial agents include identification of the infecting organism and its antimicrobial susceptibility pattern, assessment of host resistance, and assessment of risk factors.²²

There is a tendency to overtreat UTIs in patients with SCI, which contributes to antibiotic resistance. Asymptomatic infections and urine without substantial bacteriuria or pyuria should not be treated owing to a considerable risk of antimicrobial resistance. Antibiotics should not be offered for routine prophylaxis (eg, when changing indwelling catheters). The population of patients with SCI currently has higher resistance rates to a number of usual treatments for bladder infection, such as ampicillin, a combination of sulfamethoxazole and trimethoprim, and norfloxacin.²³

Case resolution

Devon is prescribed amitriptyline at bedtime, which has been effective at reducing the burning pain he had been experiencing, and the sedating side effect is helping him sleep better at night.

Given the frequency of UTIs, you ask for a renal and bladder ultrasound, which does not reveal any underlying nephrolithiasis. The bladder did appear trabeculated. You review the bladder management protocol with Devon and discover he had stopped taking mirabegron and had reduced intermittent catheterization frequency, pointing to the need for open communication between patient and physician about medication prescriptions, including cost, polypharmacy, and therapeutic substitutions.²⁴ You treat Devon for the current UTI based on the culture results, recommend resuming mirabegron, and review the clean no-touch technique for catheterization. You also help him obtain bladder management supplies through his work insurance plan so he can catheterize more regularly.

After making these changes, Devon’s spasticity reduces to the point that it no longer interferes with vehicular transfers, and no other intervention is necessary.

Conclusion

Medication management for patients with SCI is complex and specialized. Altered neurologic and cardiometabolic changes in patients with SCI make it difficult for family physicians to predict optimal medication regimens. This article highlights 3 commonly treated problems presenting in primary care among patients with SCI and data about the pharmacologic management of these issues. Strategies that can help family doctors to provide optimal treatment to their patients with SCI include open communication between patient and physician about medication prescriptions (including cost, polypharmacy, and therapeutic substitutions); interprofessional collaboration with SCI specialists and allied health providers to provide alternative (nonpharmacologic) strategies based on the patient’s physical activity, nutrition, and lifestyle management; and the Actionable Nuggets mobile app that provides brief, actionable guidance that can be used in real time with the patient in the physician’s office. For evidence-based guidelines on medication management for patients with SCI, family physicians are encouraged to use curated resources, such as Actionable Nuggets, to enhance care provided to these patients.