Effectiveness and Safety of Intrathecal Ziconotide: Final Results of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).

BACKGROUND AND OBJECTIVES: The Patient Registry of Intrathecal Ziconotide Management evaluated the long-term effectiveness and safety of intrathecal ziconotide. METHODS: The study was a prospective, multicenter observational study of intrathecal ziconotide in US clinical practice. Patients were adults with severe chronic pain that warranted intrathecal therapy. Ziconotide was initiated as the single agent in the pump; however, other intrathecal medications were permitted. The primary efficacy outcome was ≥30% reduction in numeric pain rating scale score from baseline at week 12. A secondary outcome was patient global impression of change. Adverse events were solicited at each visit. RESULTS: The registry enrolled 93 patients. Seventy-four and 28 patients completed 12 weeks and 18 months of treatment, respectively. In the overall patient population, 17.4% had ≥30% pain reduction from baseline at week 12, with a mean reduction in pain of 10.9%. At month 18, 38.5% of patients had ≥30% pain reduction from baseline, with a mean pain reduction of 24.7%. Patient-rated improvement was reported in 67% of patients at week 12 and 71% at month 18. Almost all patients experienced adverse events, the most common of which were nausea (25.8%), confusional state (22.6%), and dizziness (20.4%). CONCLUSIONS: Final study analyses showed that intrathecal ziconotide provided clinically meaningful pain relief in 17.4% and 38.5% of patients at week 12 and month 18, respectively. At these same time points, patient-rated improvement was reported in at least two-thirds of patients. The safety profile was consistent with that listed in the ziconotide prescribing information.

An Integrated Quantitative Index for Measuring Chronic Multisite Pain: The Multiple Areas of Pain (MAP) Study.

OBJECTIVE: Despite the high prevalence of chronic multisite pain, there is little consensus on methods to characterize it. Commonly used assessments report only one dimension of pain, that is, intensity, thus ignoring the spatial aspect of pain. We developed a novel pain quantification index, the Integrated Pain Quantification Index (IPQI), on a scale of 0 to 1 that integrates multiple distinct pain measures into a single value, thus representing multidimensional pain information with a single value. DESIGN: Single-visit, noninterventional, epidemiological study. SETTING: Fourteen outpatient multidisciplinary pain management programs. PATIENTS: Patients with chronic pain of the trunk and/or limbs for at least six months with average overall pain intensity of at least 5 on the numeric rating scale. METHODS: Development of IPQI was performed in a large population (N = 810) of chronic pain patients from the Multiple Areas of Pain (MAP) study. RESULTS: Prevalence of two or more noncontiguous painful areas was at 88.3% (95% confidence interval [CI] = 0.86-0.90), with a mean of 6.3 areas (SD = 5.57 areas). Prevalence of more than 10% body area in pain was at 52.8% (95% CI = 0.49-0.56), with a mean at 16.1% (17.16%). On average, IPQI values were near the middle of the scale, with mean and median IPQI at 0.52 (SD = 0.13) and 0.55, respectively. The IPQI was generalizable and clinically relevant across all domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. CONCLUSIONS: IPQI provided a single pain score for representing complex, multidimensional pain information on one scale and has implications for comparing pain populations across longitudinal clinical trials.

Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).

BACKGROUND: The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluated long-term effectiveness, safety, and tolerability of intrathecal ziconotide treatment in clinical practice. METHODS: Patient Registry of Intrathecal Ziconotide Management was an open-label, long-term, multicenter, observational study of adult patients with severe chronic pain. This interim analysis (data through July 10, 2015) of ziconotide as the first vs. not first intrathecal agent in pump included change from baseline in the Numeric Pain Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of Change (PGIC) scores. RESULTS: Enrollment closed at 93 patients; data collection was ongoing at the time of this interim analysis. Fifty-one patients (54.8%) received ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not (FIP-). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and FIP- patients, respectively. Mean (SEM) percentage changes in NPRS scores were -29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP- patients (n = 17) at month 6 and -34.4% (9.1%) in FIP+ patients (n = 14) and -3.4% (10.2%) in FIP- patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score, was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP- (n = 14) patients at month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP- (n = 7) patients at month 12. The most common adverse events (≥ 10% of patients overall as of the data cut) were nausea (19.6% vs. 7.1% of FIP+ vs. FIP- patients, respectively), confusional state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). CONCLUSIONS: Greater improvements in efficacy outcomes were observed when ziconotide was initiated as first-line intrathecal therapy vs. not first intrathecal agent in pump. The adverse event profile was consistent with the ziconotide prescribing information.

Intrathecal Drug Delivery Systems (IDDS): The Implantable Systems Performance Registry (ISPR).

OBJECTIVES: The ISPR was initially created to monitor the product performance of Medtronic implanted intrathecal drug infusion and spinal cord systems available in the United States. MATERIALS AND METHODS: Data were collected from 50 representative sites implanting and following patients with intrathecal drug delivery systems across the United States between August 7, 2003 and January 31, 2014. Device performance over time was estimated using life table survival methods. RESULTS: Of the 6093 patients enrolled in the ISPR, 3405 (55.9%) were female and 2675 (43.9%) were male, and 13 (0.2%) did not provide gender data. The average age at enrollment was 52.9 years (SD =17.6 years) and average follow-up time was 29.6 months. Currently, the estimates of device survival from pump-related events exceed 90% for all pump models across the applicable follow-up time points. The majority of product performance events were catheter-related. At 5 years of follow-up, all applicable catheter models, with the exception of revised not as designed or grafted not as designed catheters, had greater than 81% survival from catheter-related events. CONCLUSIONS: The ISPR is designed to serve as an ongoing source of system and device-related information with a focus on "real-world" safety and product performance. ISPR data continue to be used to guide future product development efforts aimed at improving product reliability and quality.

Epidural hematomas after removal of percutaneous spinal cord stimulator trial leads: two case reports.

OBJECTIVE: We report 2 cases of spinal epidural hematoma formation after the removal of percutaneous spinal cord stimulator trial leads and discuss the possible etiologies of these complications. CASE REPORT: Two patients developed spinal epidural hematomas shortly after removal of their percutaneous trial leads and required multilevel laminectomies for evacuation of the hematoma. Patient 1 reported taking aspirin the morning that his leads were pulled, whereas patient 2 had not taken aspirin in the 7 days before commencing his trial. There were 2 days between identification and evacuation of patient 1's hematoma, and he did not fully recover from the injury to his spinal cord. Patient 2 underwent surgery immediately with complete resolution of his symptoms. CONCLUSIONS: Currently, the neuromodulation community ascribes to the American Society of Regional Anesthesia and Pain Medicine guidelines, which state that nonsteroidal anti-inflammatory drugs do not significantly increase the risk for epidural hematoma with neuraxial anesthesia and, therefore, there is no need to discontinue these drugs before epidural or spinal anesthesia. We suggest that these guidelines may not be appropriate for neuromodulatory techniques that likely subject the surrounding vasculature to more trauma than neuraxial anesthesia. We recommend discontinuing nonsteroidal anti-inflammatory drugs, particularly aspirin, before neuromodulation procedures. Further investigation will establish a timeframe for holding these drugs to optimize patient safety.

Intrathecal gabapentin to treat chronic intractable noncancer pain.

BACKGROUND: Oral gabapentin is approved as an anticonvulsant medication and to treat postherpetic neuralgia. Its nonopioid properties and presumed spinal site of analgesic action made the study on intrathecal gabapentin attractive to establish the minimum effective dose for a later, pivotal trial. METHODS: The authors examined the safety and efficacy of intrathecal gabapentin in a randomized, blinded, placebo-controlled, multicenter trial in a heterogeneous cohort of candidates with chronic pain for intrathecal drug therapy. RESULTS: Patients (N = 170) were randomized to receive continuous intrathecal gabapentin (0 [placebo], 1, 6, or 30 mg/day) during 22 days of blinded treatment after implantation of a permanent drug delivery system. The highest dose, 30 mg/day, was selected to maintain a safety margin below the 100-mg/day dose that was explored in a phase 1 study. The authors found no statistically significant difference in the primary outcome measure, which was the numerical pain rating scale and response rate after 3 weeks, for any dose versus placebo. Physical functioning, quality of life, and emotional functioning also revealed no differences. Small, nonsignificant changes occurred in opioid medication use. The most frequent device-related adverse events were transient postimplant (lumbar puncture) headache, pain, and nausea. The most frequent gabapentin-related adverse events were nausea, somnolence, headache, dizziness, fatigue, and peripheral edema. CONCLUSION: Twenty-two days of intrathecal gabapentin did not demonstrate statistically significant or clinically meaningful analgesic effects. The study sponsor has no current plans for further studies. Drug-related adverse events were similar to those for oral gabapentin. Most device-related adverse events resulted from the implant surgery or anesthesia.

Trigeminal neuralgia relief with intrathecal ziconotide.

OBJECTIVE: We report a case of a 59-year-old female with severe TN who experienced satisfactory symptom relief from a single-shot trial of intrathecal ziconotide. METHOD: Performed a 1 µg single-shot trial of Prialt. RESULTS: Report of satisfaction, no side effects, and complete face and back relief briefly but most notably relief from the TN. DISCUSSION: Ziconotide should be considered for treatment of TN, although further investigation is recommended.

Meningismus associated with malpositioned intraspinal catheter for drug delivery.

BACKGROUND: Implanted delivery systems for intrathecal drug administration have become more common in the management of nonmalignant pain. Many postprocedural complications have been described in the literature including infection and headache provoked by position changes. Determining the etiology of a postimplant headache is important particularly when considering the possibility of a life-threatening infection. CASE REPORT: We present a patient who underwent placement of an implantable drug delivery system (IDDS) for intractable abdominal pain that developed positional headaches, and significant neck and back pain. Attempted cerebrospinal fluid aspiration reproduced her symptoms and imaging revealed a malpositioned intraspinal catheter tip approximated to the meninges. Revision of the system completely relieved her symptoms. CONCLUSION: Meningismus from malpositioned catheters is a rare complication that can mimic meningitis but should be considered in the differential for postimplant headaches. Given the increased use of IDDS, it is important to recognize and evaluate postimplant complication and treat it appropriately. We discuss this case report and appropriate work-up and differential diagnosis for meningismus following implant.

Clonazepam treatment of myoclonic contractions associated with high-dose opioids: case report.

A 30-year-old man with chronic abdominal pain was treated with high doses of hydromorphone intravenously and developed severe and frequent myoclonic contractions. Several medications including lorazepam failed to control the contractions; however, clonazepam in normal doses reduced the myoclonus dramatically.