Prevalence and predictors of polypharmacy among community-based individuals with traumatic spinal cord injury

Abstract

Objectives:

The objective of this study was to investigate the rate of polypharmacy and predictors in community-living people with traumatic spinal cord injury (TSCI).

Design:

Cross-sectional study.

Setting:

Outpatient clinic of the rehabilitation hospital.

Participants:

Seventy-five patients with TSCI ≥ 12 months were included in this study.

Assessments:

Demographic features were noted. American Spinal Injury Association Impairment Scale (AIS) was used to measure the neurological injury severity. Functional status was evaluated by Spinal Cord Independence Measure (SCIM) III. The Cumulative Illness Rating Scale (CIRS) was used to determine the comorbidities. Daily drug use ≥5 was considered to be polypharmacy.

Results:

The mean age was 41.3 ± 16.1 years. The mean injury duration was 55.5 ± 51.6 months. Thirty-nine (52%) patients were married, while 36 (48%) lived alone. The mean body mass index (BMI) was 25.4 ± 5.1 kg/m². AIS upper and lower extremity motor scores were 45.5 ± 11.1 and 10.3 ± 15.8, respectively. The mean SCIM III score was 56.4 ± 18.8. The mean system involvement number measured by CIRS was 5.2 ± 1.7. Fifty-two (70%) patients were motor complete, while 23 (30%) were motor incomplete. Thirty-eight (50.7%) patients had falls, 28 (37.3%) had car accidents, 6 (8%) had violence, and 3 (4%) had sports-related accidents. The rate of falling history in the last 6 months was 16% (12 patients). Polypharmacy was found in 38 (50.7%) patients. The predictors of the polypharmacy, according to the Regression analysis, were complete injury (Exp (B) i.e. Odds ratio = 7.491), advancing age (Odds ratio = 1.061) and injury duration (Odds ratio = 1.020).

Conclusion:

In this study, more than half of the patients with chronic traumatic SCI had polypharmacy. The predictors of polypharmacy were completeness, advancing age, and longer injury duration.

Introduction

Generally, polypharmacy is described as using ≥5 drugs per day.¹ Patients with multiple chronic conditions usually take many medications given by different physicians.

Polypharmacy is a well-known problem in the older population.^2–4 It is associated with increased drug side-effects, increased drug interaction, increased prescription, and heavy expense in older people.^5,6 Falling risk is high among people ≥55 years taking four or more drugs daily, especially using diuretics and drugs for central nervous system.⁷ In addition, polypharmacy may interfere with drug adherence.⁸

Polypharmacy can also be seen in people with chronic problems or multimorbidities. The secondary health problems are common in patients with spinal cord injury (SCI).^9,10 In the acute period after injury, deep vein thrombosis and heterotopic ossification prophylaxis may be required. On the other hand, comorbidities are more frequent in the chronic period. Mental health problems, gastrointestinal system, neurogenic bladder, and bone metabolism disorders are common in patients with SCI. Spasticity, pain, urinary infection, edema, and sexual dysfunction are also the other problems frequently seen in SCI.^9,10

Because of multiple comorbidities in people with SCI, they may be prone to polypharmacy. Especially the patients with SCI, who have high-level lesions or severe injuries, are under increased polypharmacy risk.¹¹ Drug side effects may be seen more frequently in SCI patients with polypharmacy.^11,12

Moreover, drug side effects are seen more frequently in SCI patients who use especially analgesic-narcotics, anti-seizure medications, and serotonergic drugs.¹²

However, while it is well known that these people are exposed to a high risk of polypharmacy, there are a few studies.^12–16 Therefore, the aim of this study was to investigate the polypharmacy rates and the predictors in community-living people with chronic traumatic SCI (TSCI).

Patients and methods

Seventy-five patients with chronic TSCI, admitted to the outpatient clinic of the rehabilitation hospital between December 2014 and 2016 were included in this study. All patients were evaluated via face-to-face interviews. Their demographic and clinical features were noted. American Spinal Injury Association Impairment Scale (AIS) was used to evaluate the severity of the injury. Spinal Cord Independence Measure (SCIM) III was used to assess the functional status. The Cumulative Illness Rating Scale (CIRS) determined the number of problems related to the systems. Daily drug use ≥5 was considered polypharmacy. Drugs used by the participants were recorded in detail.

Spinal Cord Independence Measure (SCIM) III

SCIM III is the latest version of SCIM, which has been developed in Lowenstein Rehabilitation Hospital.^17–19 SCIM III helps to find out the functional independence level in the patients with SCI. Functional independence in self-care, respiration, and sphincter management, and mobility areas can be evaluated with 19 items. The total score is between 0 and 100. The validity and reliability of the Turkish version of SCIM III have been studied.²⁰

Cumulative Ilness Rating Scale (CIRS)

CIRS is used to define multiple system problems.^21,22 CIRS was first developed by Linn et al.²¹ for measuring comorbidities related to 13 systems. Every system problem was inquired with a score between 0 and 4. Afterward, CIRS was modified by Miller et al.²³ for evaluating 14 system-related disorders, including cardiac, vascular, hematologic, respiratory, otorhinolaryngologic, upper gastrointestinal, lower gastrointestinal, hepatic and pancreatic, renal, genitourinary, musculoskeletal and dermatologic, neurologic, endocrine, metabolic, breast, and psychiatric problems.

Statistics

The Shapiro Wilk test and Lilliefors Significance Correction were used to test the normal distribution of data . Continuous variables were summarized as an arithmetic mean (standard deviation [SD]) or a median (interquartile range). Categorical data were summarized as frequency and analyzed using the Likelihood Ratio test and Fisher’s exact test. Means of the two groups were compared using Mann–Whitney U test or unpaired-sample t-test. A multivariate binary logistic regression analysis was performed to determine risk factors for polypharmacy. The P value for a factorincluded in the regression model was 0.05 using the forward conditional method, and the P value for exclusion was 0.1. The suitability of the regression model was reviewed with the Hosmer–Lemeshow test. The regression model was considered statistically suitable if the P value found with the Hosmer–Lemeshow test was <0.05. The 95% confidence intervals were calculated for the odds ratios [Exp(B)]. The Wald statistical analysis was conducted to determine the significance of coefficient B. P < 0.05 was considered significant. The software package used for data management was PASW Statistic 18.

Ethics

All participants were informed about the study and their written concent was obtained. This study was approved by the local ethics committee.

Results

The mean age was 41.3 ± 16.1 years. Twenty (26.7%) were female. The mean injury duration was 55.5 ± 51.6 months. The mean body mass index (BMI) was 25.4 ± 5.1 kg/m². The upper and lower extremity motor scores were 45.5 ± 11.1 and 10.3 ± 15.8, respectively. The mean SCIM III score was 56.4 ± 18.8. The mean number of involved systems was 5.2 ± 1.7. Fifty-two (70%) were motor complete, and 23 (30%) were motor incomplete. In the etiology of TSCI, 38 (50.7%) patients had falls, 28 (37.3%) had car accidents, 6 (8%) had violence, and 3 (4%) had sports accidents.

Demographic and clinical features of the patients are shown in Table 1 and Table 2.

Table 1.

Clinical characteristics of the patients with and without polypharmacy.

	Without polypharmacy	With polypharmacy	P value
Age (years)	31.00 (22.00)	47.00 (22.75)	0.000*
Body height (cm)	170.00 (11.50)	171.00 (11.75)	0.865*
Body weight (kg)	69.00 (23.50)	76.00 (13.50)	0.006*
Body mass index (kg/m2)	22.58 (6.21)	26.29 (5.58)	0.002*
Disease duration (mo)	26.00 (28.50)	57.00 (85.25)	0.006*
SCIM III score	58.6 (19.0)	54.3 (18.6)	0.325**
CIRS score	4.00 (1.00)	6.00 (2.25)	0.000*
Upper extremity motor score	50.00 (0.00)	50.00 (0.00)	0.662*
Lower extremity motor score	0.00 (28.50)	0.00 (2.00)	0.039*
Complete injury (n [%])	22 (59.5)	30 (78.9)	0.114***

*Data were given as median (interquartile range), and Mann Whitney U-test was used for comparison.

**Data were given as arithmetic mean (standard deviation), and an unpaired t-test was used for comparison.

***Data were given as n (%), and Yate’s corrected Chi-square test was used for comparison.

SCIM III, Spinal Cord Injury Measure III score; CIRS, Cumulative Illness Rating Scale.

Table 2.

Demographic and clinical characteristics of the patients with and without polypharmacy.

	With polypharmacy	Without polypharmacy	P
Sex
Female	9	11	0.848*
Male	28	27
Marital status
Married	16	23	0.205*
Single	21	15
Injury level
Paraplegia	28	29	1.0*
Tetraplegia	9	9
Etiology
Violence	3	3	1.0**
Accident	34	35
Ambulation
Ambulatory	30	28	0.625*
Nonambulatory	7	10
SCIM III
Low (0–34)	4	7	0.545*
High (35+)	33	31

* Yate’s corrected Chi-square test, ** Fisher exact test.

SCIM III, Spinal Cord Injury Measure III score.

The mean age, body weight, body mass index (BMI), time since injury, and CIRS score were significantly higher in the patients with polypharmacy. The lower extremity motor score was considerably lower in the patients with polypharmacy compared to the group who had <5 daily medications. System-related problems in SCI are shown in Fig. 1.

Figure 1.

Frequency of the affected systems among the people with spinal cord injury ORL, Otolaringology; GIS, Gastrointestinal system; GUS, Genitourinary system.

Thirty-eight patients (50.7%) had polypharmacy. Motor completeness rates defined according to AIS classification rates were 78.9% (n=30) and 59.4% (n=22) in the patients with and without polypharmacy, respectively. Motor incompleteness rates among the patients with and without polypharmacy were 30.1% (n=8) and 40.5% (n=15), respectively. Drugs used by the whole group are shown in Fig. 2. The most frequent drugs were anti-muscarinic drugs (80%), pregabalin and gabapentin for neuropathic pain (78.7%), and anti-spasticity drugs (66.6%).

Figure 2.

Frequency of the most used drugs among the people with spinal cord injury.

In this study, among 31 SCI patients with polypharmacy, the most frequently used drug combination was the combination of anti-spasticity drugs, anti-muscarinic drugs, and gabapentinoid drugs for neuropathic pain, which was used in 20 patients (64.5%). The second common combination consisted of anti-spasticity drugs, anti-muscarinic drugs, and anti-depressants drugs, which were used in 10 patients (32.2%).

The binary logistic regression analysis revealed that age, injury duration, and completeness were the predictors of polypharmacy (Nagelkerke R²=0.473, the Hosmer–Lemeshow test P=0.570). The risk of polypharmacy was 7.49 times higher in patients with complete SCI than in patients with incomplete SCI (Table 3).

Table 3.

Regression model for polypharmacy.

Independent variable	B	SE	Wald	df	P value	Odds ratio	95% CI
							Lower limit	Upper limit
Age (yrs)	0.073	0.021	11.613	1	0.001	1.076	1.032	1.122
Injury duration (mo)	0.025	0.009	8.047	1	0.005	1.025	1.008	1.043
Completeness	2.014	0.739	7.416	1	0.006	7.491	1.758	31.914
Constant	−5.608	1.361	16.989	1	0.000	0.004

*Reference categories are “Complete spinal cord injury” for completeness.

SE, Standard error; df, degrees of freedom; CI, confidence interval.

Discussion

In this study, the polypharmacy rate was 50.7% in people with TSCI living in the community. In previous studies it has been reported that polypharmacy can be seen in 30.8–66% of patients with SCI.^12–16 Kitzman et al.¹² reported that the polypharmacy rate was 56% in 13160 patients with SCI in a retrospective case-control study. The authors also concluded that the rate of polypharmacy, high-risk drug use, and problems related to the drugs were high in SCI.¹² And also, polypharmacy rates in patients with paraplegia and tetraplegia were 65% and 66%, respectively. Moreover, the polypharmacy rate was 27% in the control group.

Hwang M et al.¹⁴ concluded that the polypharmacy rate was 30.8% in 159 adult patients with primary pediatric SCI whose mean injury duration was 21.2 ± 7.2 years, and the mean age was 35.0 ± 6.2 years. The authors reported that polypharmacy rates in patients with tetraplegia and paraplegia were 40.2% and 17.9%, respectively. The polypharmacy rate was lower in this previous study than that of ours, because patients were younger and had pediatric SCI.

Patel et al.¹⁵ concluded that the polypharmacy rate was 74%, including vitamins and minerals, and 63%, including only prescription and non-prescription drugs in 19 SCI patients with a mean age of 46.7 years. In another study, the polypharmacy rate was 35.8% in people ≥62 years, living in the community.²⁴ The polypharmacy rate was higher in our study among the patients with TSCI than the elderly people in that study.

The most frequently prescribed drugs in people with SCI were anti-muscarinic (80%), anti-seizure medications for neuropathic pain (78.7%), anti-spasticity agents (66.6%), anti-depressants (52%), bowel agents (49.3%), calcium (49.3%), and proton pump inhibitors (44%) in this study. The most common drugs have been muscle relaxants (50.3%), bladder medications (48.5%), bowel agents (41.5%), analgesics (26.4%), and anti-depressants (16.9%) in SCI in a previous study.¹⁴ Injury duration was longer in the previous study than that of the patients in our study.

Rouleau and Guertin¹⁶ suggested that the most frequently used drugs by patients with chronic TSCI were bisphosphonates, bronchodilators, lipid regulators and anti-inflammatory drugs. In the same study, most frequently used medications in patients with traumatic and non-traumatic SCI were used for bowel and bladder problems, venous thromboembolism, cardiovascular problems, mood problems, gastrointestinal problems, infections, inflammation, sleep problems, pain, and vitamin D deficiency (35–66%).

Patel et al.¹⁵ concluded that the most frequently used drugs were for pain (n=13.68%), constipation (n=8.42%), muscle spasm (n=8.42%), hypertension (n=8.42%), and depression (n=7.37%) in the people with SCI in a primary-care based clinic.

In this study, the most frequently used drug combination in SCI patients with polypharmacy was the combination of anti-spasticity drugs, anti-muscarinic drugs, and gabapentinoid drugs for neuropathic pain (64.5%). The second common combination consisted of anti-spasticity drugs, anti-muscarinic drugs, and anti-depressants (32.2%).

Also, Kitzman et al¹² reported that high-risk drugs, such as analgesic-narcotics, anti-seizure medications, anti-depressants, and muscle relaxing agents, were used in patients with SCI.

Both anti-spasticity and anti-depressant agents may have side effects, such as dizziness and weakness, which may become more apparent in the combination of these drugs. The combined use of anti-depressants and opioid analgesics may lead to the serotonergic syndrome. Polypharmacy and associated drug-related problems may affect spinal cord injury rehabilitation.¹²

In this study, the predictors of polypharmacy were completeness, advancing age, and injury duration. In the polypharmacy group, age, body weight, BMI, injury duration, and CIRS score were significantly higher. Moreover, lower extremity motor score is significantly lower in the polypharmacy group. The predictors of polypharmacy have been aging, longer injury duration, and secondary health problems in a previous study.¹⁴ Jensen and Biering-Sørensen¹³ concluded that the patients who have a more severe injury according to AIS classification carry the risk of frequent drug use.

The most common system problems were neurologic, genitourinary, musculoskeletal and dermatologic, endocrine, metabolic and breast, and psychiatric by 100%, 80%, 73.3%, 57.3% and 50.7%, respectively. Patel et al.¹⁵ reported that the frequencies of the comorbidities were depression/anxiety (37%), osteoporosis/osteopenia (26%), hypertension (21%), dyslipidemia (21%), osteoarthritis (21%), constipation (16%), peripheral vascular disease (16%), incontinence (16%), and hypothyroidism (16%). Moreover, they suggested that asthma, diabetes mellitus, gastroesophageal disease, myocardial infarction/heart failure, stroke/transient ischemic attack, and atrial fibrillation were rarely seen.

Brinkhof et al.¹⁰ suggested that the comorbidity rates were high. Most frequent health problems were spasticity (74%), chronic pain (73.2%), bladder (66.2%), and bowel dysfunctions (64.6%) in the traumatic or non-traumatic SCI patients with a mean of 14 years injury duration. Adriensen et al.⁹ reported that the most common health problems were musculoskeletal (63.5%) and neuropathic painful situations (34.1%), urinary infections (33.3%) and pressure sores (29.4%), and neurogenic bladder (27%) in the patients with traumatic or non-traumatic SCI for 10 years or longer.

This study has some strengths and limitations. A strength is that all the patients were evaluated by face-to-face interviews. Drug side effects and drug interactions were not evaluated because of the cross-sectional design in this study. The lack of information about the effects of polypharmacy on rehabilitation outcomes is another limitation of the study.

However, the side effects of non-prescription drugs, vitamins, and drugs have not been investigated. Being a single-center study was the other limitation of the study.

More than half of the patients with chronic TSCI had polypharmacy in this study. The most frequently used drug groups were bladder agents, neuropathic pain, and anti-spasticity medications. The predictors of polypharmacy were complete injury, advancing age, and injury duration in patients with TSCI.

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