Despite the anticipated benefits of intrathecal drug delivery, few specialists truly appreciate its potential. This underappreciation was the topic of discussion during a recent panel, “New Innovations in Targeted Drug Delivery,” at the 2024 American Society of Pain & Neuroscience (ASPN) annual conference.
Delivering drugs by oral or parenteral routes may be limited by the blood–brain barrier, which prevents macromolecules and other substances from reaching the central nervous system. Intrathecal therapy allows for direct access to the cerebrospinal fluid by bypassing the blood–brain barrier or first-pass metabolism.
“Pumps were often utilized as last resort in challenging cases, often as a miracle cure, which didn’t prove to be true,” said Neel Mehta, MD, the division chief of pain management at Weill Cornell Medicine, in New York City, and a panel member at ASPN. “As a result, this left an unsatisfactory taste for fellows and trainees that led them to feel like this therapy didn’t have true efficacy. It’s quite the opposite, and in the right selected patient, it can be very efficacious.”
Mechanics of Intrathecal Pump Therapy
Targeted intrathecal drug delivery (TIDD) is typically placed by a spine surgeon, neurosurgeon or pain specialist. Pain specialists typically then manage the device including dose adjustment and refills.
Components of the TIDD system include a pump and an intrathecal catheter. The pump serves as a drug reservoir and is implanted under the subcutaneous tissue in the abdominal area. Catheter tip placement is at the spinal cord level innervating the region of the pain source. Intrathecally delivered drugs suffuse the pia mater, arachnoid and white matter of the spinal cord to target the dorsal horn receptors and ion channels involved in nociceptive processing and transmission (Shah N, et al. Implantable intrathecal drug delivery system. Updated 2024 Mar 16. In: StatPearls [internet]. StatPearls Publishing; 2024 Jan. https://www.ncbi.nlm.nih.gov/books/ NBK538237/ ).
A computer is used to program the pump mechanism to deliver desired dosages, such as a steady flow, at night or in the morning. A remote also can be given to the patient to deliver extra doses. The pump can be left in for years and replaced as needed at the end of the battery life, with the drug reservoir refilled every few months on average.
“Advantages of the pump include flexibility of dosing, smaller dose size and more accuracy compared to oral or IV medication,” Mehta told Pain Medicine News. “Patients can shower, swim and travel with the pump. It doesn’t impact their life.”
Uses of Intrathecal Pump Delivery
TIDD is well accepted for the treatment for spasticity and intractable cancer-related pain. Furthermore, patients struggling with chronic pain that is refractory to conventional and minimally invasive treatments, as well as those suffering from severe adverse effects of oral, rectal or transdermal opioid administration, may benefit. Some noncancer pain indications include neuropathic pain, peripheral neuropathy, postherpetic neuralgia and mixed nociceptive–neuropathic pain syndromes.
Intrathecal infusions of morphine and ziconotide are approved by the FDA as single agents for the treatment of chronic pain. The FDA has also approved intrathecal baclofen for the management of cerebral spasticity (e.g., traumatic brain injury) that is unresponsive to maximal doses of oral baclofen, tizanidine or dantrolene (Ghanavatian S, et al. Baclofen. Updated 2024 Aug 11. In: StatPearls [internet]. StatPearls Publishing; 2024 Jan. https://www.ncbi.nlm.nih.gov/books/ NBK526037/ ).
TIDD affords a substantial reduction in analgesic dose. For instance, the spinal daily dose of morphine can be decreased by a factor of 12 to 300 versus the oral daily dose, thereby reducing the incidence of systemic adverse effects (Best Pract Res Clin Anaesthesiol 2023;37[2]:157-169).
“The body needs a lower dose of medication to achieve the same benefit,” Mehta said. “You have less sedation, less nausea, less constipation and better pain relief.”
Although rare, TIDD complications include infection, device malfunction, catheter kinking, granuloma formation and fibrosis.
TIDD Underutilization
Many pain specialists don’t offer TIDD to their patients, according to Mehta.
“It’s not always used. Not a lot of doctors feel comfortable using it. Many doctors who go through fellowship training haven’t been exposed to this therapy. The national usage of this pump is concentrated in a handful of centers that do it in high volume,” he said. And noted that, fortunately, patients being treated at NewYork-Presbyterian Hospital and Memorial Sloan Kettering Cancer Center (MSKCC) have access to this important therapy.
“If you are training, and all cases you see are patients who failed everything else and then are placed on the pump, you don’t see dramatic improvements. You then assume pumps aren’t useful. But if we use it early and have better patient selection, there are a lot of successes,” he added.
In his practice, Mehta avers that pump therapy has dramatically improved quality of life in patients with spinal stenosis, vertebral fractures and so forth. In many cases, the effectiveness of TIDD has surpassed other options including spinal cord stimulation.
In an interview with Pain Medicine News, Amitabh Gulati, MD, the director of chronic pain at MSKCC, in New York City, and co-chair of the ASPN panel, concurred that lack of fellowship training has affected pump usage.
“Due to the education gap, we’re seeing less integration of pump therapy in fellowship curricula than we had 20 years ago. This has led to stagnancy of growth, whereas other neuromodulation devices are being more utilized. The controversy is how intrathecal drug delivery fits into a treatment algorithm for treating chronic pain patients,” he explained.
Mehta said other concerns about the pump are financial, with maintenance considered costly. One potential solution involves the employment of advanced practice providers to help with patient management. Home infusion centers also can decrease the maintenance burden on practices.
Promoting Pump Use
A goal of the panel at ASPN was to promote the use of TIDD. One solution offered could be increased education at the postgraduate level.
“If we don’t spend time training people about pump therapy and showing the successes in training, it will be one of those technologies that disappears and that will be a real loss to the patient community,” Mehta said.
He noted that pump therapy shouldn’t be viewed as “salvage therapy.” Instead, he recommended, “think about pumps earlier before escalating opioids. We could have improved quality of life all along if these pumps are placed earlier.”
The key to providing the pump as an earlier option could be improved communication between pain specialists, oncologists and palliative care specialists.
For pain medicine specialists who want to learn more about pump management, complications, etc., Gulati recommended continuing medical education, society and industry advocacy efforts, and understanding guidelines such as the Polyanalgesic Consensus Conference recommendations.
“Intrathecal drug delivery advocates, such as ourselves, are committed to having physicians learn from our group so they can help their patients with this therapy in the future,” he offered.
—Naveed Saleh, MD, MS
Gulati reported relevant consulting for AIS Healthcare, Medtronic and TerSera Medical. He reported unrelated consulting for Hinge Health, Nalu Medical, Neurovasis and SPR Therapeutics. Mehta reported no relevant financial disclosures.