Spinal Cord Stimulation and Psychotropic Medication Use: Missing Piece to the Puzzle?

Abstract

Psychotropic medications have modulatory effects on spinal cord stimulator (SCS) therapy and may play an important role in determining treatment success in chronic pain management. However, it remains unknown how SCS affects psychotropic use and whether the medications affect outcome. We performed a retrospective study to determine the prevalence of psychotropic medication (i.e. anxiolytic, antidepressant, and anticonvulsant) use among new SCS patients immediately before implantation and characterized the dosage changes at 1-year. We also sought to understand whether pre-operative medication status affects outcome, defined as device explantation due to treatment failure. In an analysis of 45 patients, 31%, 51% and 71% were actively taking anxiolytics, antidepressants, and anticonvulsants, respectively, before surgery. In the majority of cases, daily dosages remained the same for all three classes of medication at 1-year. Patients who were on two or more classes of medications pre-operatively had significantly lower explantation rate compared to those with one or none (12% vs. 43%, p=0.041) and had 5.25 times less likelihood of explanation in the future (OR 5.25, 95%CI 1.18–23.2, p = 0.029). Our study suggest that peri-operative multimodality medical treatment may enhance the therapeutic efficacy and durability of SCS in carefully selected chronic pain patients.

Introduction

Chronic pain is a significant problem worldwide and is associated with profound physical and psychological morbidity in affected patients [1–5]. Spinal cord stimulation (SCS) is a surgical treatment option that is considered for intractable pain disorders when other forms of therapy have failed [1,6]. Much attention has recently been placed on opioid and SCS therapies due to the ongoing opioid crisis. However, SCS patients are rarely only prescribed opioids as sole treatment agents. In addition to nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic anticonvulsants, such as gabapentin, are commonly used for chronic pain management [7,8]. Anxiolytics and antidepressants are also often prescribed due to high rates of concurrent psychiatric conditions [3,9,10].

Anxiolytics, antidepressants, and anticonvulsants significantly influence how pain is perceived and experienced, and may play a pivotal role in achieving therapeutic success in SCS patients [3–5]. However, very few studies have reported the prevalence of these commonly prescribed psychotropic medications among chronic pain patients who undergo SCS implantation [2,7,8]. Also, it remains unknown whether SCS therapy affects the usage of these medications and how the medications, in turn, impact outcome after SCS. Understanding the role that different medication classes play can improve risk assessment, outcome prediction, and clinical management of SCS patients. Thus, we performed a retrospective study to determine the pre-operative prevalence of anxiolytic, antidepressant, and anticonvulsant use in a cohort of new SCS patients and the dosage changes 1-year after SCS implantation. We also sought to understand whether pre-operative medication status affects SCS outcome, defined as explantation due to treatment failure.

Methods

Patients presenting to the Johns Hopkins Department of Neurosurgery between April 2011 and February 2018 for their first SCS implantation surgery were identified. Electronic medical records were reviewed to obtain demographic information, implantation surgery date, and lists of active anxiolytic, antipsychotic, and antidepressant medications at immediately pre-operative and 1-year follow-up clinic visits. Medication name, class, and dosages were recorded. Benzodiazepines including alprazolam, clonazepam, lorazepam, and diazepam, and nonbenzodiazepines, including buspirone, zolpidem, and eszopiclone, were classified as anxiolytics. Serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants were classified as antidepressants. The most common antidepressants were duloxetine, buproprion, trazodone, amitriptyline, escitalopram, and mirtazapine. Analgesic anticonvulsants, such as gabapentin, pregabalin, and topiramate were included. Daily total dose of each medication before and 1-year after surgery was compared and categorized as either increased, decreased, or unchanged. All 45 underwent successful percutaneous trial lead placement prior to permanent SCS implantation. Of the 47 patients identified, 45 (96%) had 1-year follow-up and medication information. Twelve patients (27%) underwent SCS removal due to treatment failure at the time of the analysis. SAS JMP Pro Version 14 (SAS Institute Inc. Cary, NC) was used for statistical analysis. Student’s t-test and Fisher’s exact test were used for continuous and categorical variables, respectively. The study was approved by the Johns Hopkins IRB (IRB00068382).

Results

Average age of our cohort was 65 years and 58% (n=26) were women. Before SCS implantation, 14 (31%), 23 (51%) and 32 (71%) patients were actively taking anxiolytics, antidepressants, and anticonvulsants, respectively. Twenty-four (53%) of patients were on two or more classes of medications. Pre-operative psychotropic medication use in our cohort is presented in Table 1. In most cases, daily dosage remained the same for all three classes of medication one year after SCS implantation (Figure 1). Most noticeable changes were seen with the anticonvulsants (Figure 1). Thirty-three (73%) patients retained their SCS implants. SCS removal rate in our cohort was 9% (n=4) at 1 year, 18% (n=8) at 2 year, and 27% (n = 12) at the time of analysis (median 41 months post implantation). Median time to removal was 18 months. A majority of patients who eventually underwent SCS removal were either on none or one psychotropic class immediately before implantation (Table 1). Patients who were on two or more classes immediately prior to SCS implantation had significantly lower explant rate (12% vs. 43%, p=0.041) and 5.25 times less likelihood to undergo SCS explantation in the future compared to those with one or none (OR 5.25, 95%CI 1.18–23.2, p = 0.029).

Table 1.

Pre-operative psychotropic medication (i.e. anxiolytic, antidepressant, and anticonvulsant) use and spinal cord stimulator explantation outcome.

Number of concurrent medication classes	Total patients (n = 45)	Explanted patients(n = 12)	Months from implantation (mean ± SD)
0	6	4	23 ± 8
1	15	5	18 ± 16
2	18	2	57
3	6	1	40

Figure 1.

Distribution of patients based on changes in daily dosages per medication class between immediately before spinal cord stimulator implantation and 1-year after surgery.

Discussion

In our cohort, many patients were on psychotropic medications prior to SCS implantation and combination therapy was common. Furthermore, dosages of all three classes remained unchanged in a majority of patients at 1-year. Although some may argue that medication reduction is ideal, unchanged dosages may be an indication of stability and tolerability of symptoms. Anticonvulsants were associated with more frequent post-operative dosage modification than other classes, possibly due to worsening neuropathic pain or uncomfortable stimulation related paresthesias. Also, it may reflect the general comfort level of the clinician with anticonvulsants compared to other types of psychotropics in chronic pain management.

Our SCS removal rates at 1- and 2-years were consistent with other larger studies [1,11,12]. Notably, explanation beyond the 2-year mark was not uncommon in our cohort. Few studies have reported long-term explantation rates, which must be explored further to define the true long-term durability of SCS therapy. In our cohort, being on two or more classes of psychotropic medications immediately before surgery was associated with significantly lower risk of SCS removal. Additionally, the three explantation surgeries in this subgroup were markedly delayed at 40, 42 and 72 months after the index surgery. Together, these findings suggest that peri-operative multimodality medical treatment may enhance the therapeutic efficacy and durability of SCS in carefully selected chronic pain patients. Also, medical management should be thoroughly explored before proceeding with SCS to reduce unnecessary surgeries in patients with high risk of treatment failure. Comprehensive evaluation, including pain and psychiatric assessments, by a multidisciplinary team early in the course of management, and specifically prior to SCS implantation, may be critical to successful outcome [3,5]. Further investigation with larger cohorts is urgently needed to understand how SCS affects psychotropic medication use, and how these medications, in turn, influence outcome. Also, an optimal pharmaceutical regimen that can synergistically enhance the efficacy of SCS needs to be identified to better combat the opioid crisis and improve the lives of chronic pain patients.

Conclusion

Concomitant psychotropic medication use is common among chronic pain patients who undergo SCS implantation. SCS therapy is associated with stability in the psychotropic medication dosages in a majority of patients at 1-year. Also, being on two or more classes of psychotropics is associated with significantly lower explanation rate at long-term follow-up. Our study underscores the importance of peri-operative multidisciplinary assessment and multimodality medical management and the critical need to investigate the role that psychotropic medications play in SCS patients.

Highlights.

• Psychotropic medication use is common among chronic pain patients who undergo spinal cord stimulator implantation.

• Spinal cord stimulation therapy often does not lead to changes in daily psychotropic medication requirements within 1 year after implantation

• Patients who were on two or more classes of psychotropic medications at the time of spinal cord stimulator implantation were five times less likely to undergo device explanation for treatment failure.

• Multimodal medical therapy may enhance the efficacy of spinal cord stimulation therapy.