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Treatment Groups and Patient Outcomes

The study examined treatment groups based on the patient global impression of change and those achieving ≥30% or ≥50% pain reduction. The findings were largely negative and disappointing, attributed to factors like insufficient study power, patient heterogeneity, small contributions from 33 study centers in Japan, potential genetic influences, and the presence of numerous uncontrolled concurrent medications. The study also reported an unusually high placebo response, likely due to the 2:1 (treatment: placebo) enrollment design, which may have inflated patient expectations. In a specific case, a 68-year-old patient with trigeminal PHN failed to achieve pain relief with a complex regimen including gabapentin (1800 mg/day), oxcarbazepine (600 mg/day), amitriptyline (20 mg/day), and tapentadol (500 mg/day).

Tapentadol and Diabetic Painful Neuropathy (DPN)

A randomized controlled trial (RCT) by Tominaga et al revealed that prolonged-release (PR) tapentadol failed to outperform placebo in 18 patients with diabetic painful neuropathy (DPN). Pain scores on a numerical rating scale (NRS) decreased by 2.9±2.43 in the placebo group and 2.8±2.24 in the tapentadol group, showing no significant difference. Similar to the PHN study, flaws in the DPN study design may have contributed to the lack of efficacy.

In a phase III RCT conducted by Schwartz et al, 588 DPN patients with pain scores of ≥5 on the NRS, who had poor responses to previous treatments, were enrolled. Patients were titrated to an optimal dose of tapentadol PR (200–500 mg/day) over three weeks in an open-label phase. Of the 395 patients showing at least a 1-point reduction in pain intensity, 196 were assigned to tapentadol PR, and 199 to placebo for a 12-week double-blind phase. The primary outcome was the change in average pain NRS, which showed a mean difference of −1.3 (95% CI: −1.70 to −0.92, P<0.001) between tapentadol and placebo groups, favoring tapentadol. A ≥30% improvement in pain intensity was reported by 61% of patients during the open-label phase, and 54% of those on tapentadol PR maintained this improvement to week 12. No new safety concerns emerged.

These findings were supported by another RCT with a similar design, where 358 patients completed titration. Among them, 166 received tapentadol PR, and 152 received placebo. Mean pain scores dropped from 7.33±1.30 at baseline to 4.16±2.12 after titration. During the 12-week double-blind phase, mean pain reduction was −0.95 (95% CI: −1.42 to −0.49, P<0.001) in favor of tapentadol PR.

Pooled Analysis and Subgroup Efficacy

In 2015, Schwartz et al performed a pooled analysis of these two studies, involving 588 patients. Over 12 weeks, the mean change in pain intensity from baseline was −1.14 (95% CI: −1.43 to −0.84, P<0.001), favoring tapentadol PR. The benefit was consistent across patient subgroups defined by age, gender, ethnicity, prior opioid use, and pain intensity. The improved pain outcomes were paralleled by better quality of life, and response rates further underscored tapentadol’s efficacy.

Mechanistic Study in DPN

Niesters et al conducted a double-blind mechanistic RCT involving 24 DPN patients treated with either placebo or sustained-release (SR) tapentadol for four weeks. Patients met specific criteria for neuropathic pain, including dysesthesias, paresthesias, burning pain, and abnormal sensory thresholds. Weekly assessments included pain on a visual analog scale (VAS) and two functional measures: conditioned pain modulation and offset analgesia. Tapentadol SR significantly reduced pain compared to placebo, with VAS scores decreasing from 6.5±0.6 to 3.9±0.6 (P=0.03). Conditioned pain responses improved more with tapentadol (24.2±7.7%) than placebo (14.3±7.2%, P<0.001). The results suggest that tapentadol SR enhances neuropathic pain relief by modulating descending pain inhibitory pathways from the brainstem to the spinal cord.

Diabetic pain can include pain associated with peripheral artery disease. A study of 2,514 diabetic patients experiencing lower limb pain revealed that 9% had diabetic peripheral neuropathy (DPN) alone, 8.5% had peripheral artery disease alone, and 2.4% had both conditions, collectively referred to as lower-extremity disease. Peripheral artery disease can produce mixed pain with both nociceptive and neuropathic components, requiring treatment that addresses both types of pain. Due to its dual mechanism of action, tapentadol may be a suitable option for such cases.

Tedeschi et al. evaluated a three-month treatment with tapentadol PR (mean dose 186.4 ± 56.0 mg/day) in 25 diabetic patients with lower-extremity peripheral artery disease. Most patients (96%) had skin ulcers, and 72% experienced neuropathic pain (intense paresthesia and allodynia). After three months, pain levels on the Numeric Rating Scale (NRS) decreased significantly from 7.9 ± 1.2 to 2.8 ± 2.3, while neuropathic pain scores (DN4) dropped from 4.0 ± 1.2 to 1.2 ± 1.5, with the number of neuropathic pain patients decreasing from 72% to 16% (P<0.01). Additionally, quality of sleep and health-related physical and mental components significantly improved, supporting tapentadol PR's potential efficacy for this condition.

Tapentadol for Chemotherapy-Induced Neuropathy (CIPN)

In a prospective three-month open-label study, Galiè et al. assessed tapentadol's efficacy in 31 patients with moderate-to-severe neuropathic pain from CIPN unresponsive to maximum doses of antidepressants and anticonvulsants. Most cases were linked to treatments with taxane (45%) or platinum agents (32%), primarily for breast and digestive cancers. Tapentadol, titrated to a mean dose of 200 mg/day, reduced average DN4 scores from 6.36 ± 1.4 to 4.18 ± 0.73 over three months. Nerve conduction studies showed no significant changes, suggesting tapentadol relieved pain without altering nerve damage.

Tapentadol in Musculoskeletal Pain with Neuropathic Components

Musculoskeletal conditions, including chronic low back pain (CLBP) and chronic neck pain (CNP), are major causes of disability. These conditions often involve mixed pain, with nociceptive and neuropathic components. Radicular neuropathic pain is commonly associated with CLBP and CNP, while osteoarthritis and rheumatoid arthritis can also exhibit neuropathic components due to pathological changes in articular nerves. Neuropathic symptoms may explain sensory abnormalities like hyperalgesia, allodynia, and reduced proprioception seen in osteoarthritis patients.

The prevalence of neuropathic pain in CLBP has been estimated to range from 16.7% to 54.4%, depending on the diagnostic method. Studies show that patients with neuropathic components experience more severe and prolonged pain, along with higher rates of psychiatric comorbidities and disability. Tapentadol PR has shown promise in treating CLBP with neuropathic components.

In one study, patients received tapentadol PR (100–500 mg/day) during a five-week titration phase, followed by a seven-week maintenance period. Tapentadol significantly reduced neuropathic symptoms, with a mean PDQ score reduction of 3.02 ± 2.07 (P<0.0001). Lower doses were effective in patients with a higher likelihood of neuropathic pain. Another phase IIIb study confirmed these findings, where patients with severe CLBP and neuropathic components responded well to tapentadol PR (300 mg/day), with significant improvements in symptoms and quality of life.

These studies highlight tapentadol's efficacy in managing pain with neuropathic components across various conditions, improving both symptom relief and quality of life for patients.

What Is a Neurosurgeon?

A neurosurgeon is a medical specialist who has completed additional schooling and training, which provides the skills necessary for diagnosing and treating a range of conditions affecting the central and peripheral nervous system.

Following our four years of pre-med and four years of med school, we also completed a one-year general surgery internship and five to seven years in neurosurgery residency. Additionally, we further our education and stay current through continuing education programs, racking up hundreds of hours every year.

Simply put, we treat problems that affect your brain, your spine, and your nerves. These conditions can often stump doctors who haven’t completed the same extensive training as we have.