Long-term controlled-release oxycodone and pregabalin in the treatment of non-cancer pain: an observational study.
ABSTRACT This study evaluates the efficacy and tolerability of long-term controlled-release (CR) oxycodone + pregabalin in patients with non-cancer pain, in a real-life setting.
Patients (n = 1,051) with chronic uncontrolled non-cancer pain received CR oxycodone + pregabalin for 1 year. Pain intensity was rated on an 11-point numerical rating scale (NRS) at months 1, 2, 4, 6, 9 and 12.
Throughout the study period, the NRS score decreased significantly (baseline: 7.02 ± 1.26; 12 months: 1.45 ± 0.92; p = 0.00001). Following an initial increase in the mean daily doses of CR oxycodone (starting dose: 12.5 ± 8.4 mg) and pregabalin (starting dose: 121.7 ± 97.2 mg), dose reductions were seen for both drugs with the trend particularly evident for CR oxycodone. 23% of patients withdrew from the study, mainly due to adverse events (67.9% of withdrawn subjects). However, 19.7% of withdrawn patients were removed from the study due to complete relief from chronic pain. The combination was generally well tolerated and there were no reports of addiction.
The combination of CR oxycodone + pregabalin could represent a valuable long-term therapeutic addition to existing pharmacological options for the treatment of non-cancer pain.
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ABSTRACT: This is a structured evidence-based review of all available studies on the development of abuse/addiction and aberrant drug-related behaviors (ADRBs) in chronic pain patients (CPPs) with nonmalignant pain on exposure to chronic opioid analgesic therapy (COAT). To determine what percentage of CPPs develop abuse/addiction and/or ADRBs on COAT exposure. Computer and manual literature searches yielded 79 references that addressed this area of study. Twelve of the studies were excluded from detailed review based on exclusion criteria important to this area. Sixty-seven studies were reviewed in detail and sorted according to whether they reported percentages of CPPs developing abuse/addiction or developing ADRBs, or percentages diagnosed with alcohol/illicit drug use as determined by urine toxicology. Study characteristics were abstracted into tabular form, and each report was characterized according to the type of study it represented based on the Agency for Health Care Policy and Research Guidelines. Each study was independently evaluated by two raters according to 12 quality criteria and a quality score calculated. Studies were not utilized in the calculations unless their quality score (utilizing both raters) was greater than 65%. Within each of the above study groupings, the total number of CPPs exposed to opioids on COAT treatment was calculated. Similarly, the total number of CPPs in each grouping demonstrating abuse/addiction, ADRBs, or alcohol/illicit drug use was also calculated. Finally, a percentage for each of these behaviors was calculated in each grouping, utilizing the total number of CPPs exposed to opioids in each grouping. All 67 reports had quality scores greater than 65%. For the abuse/addiction grouping there were 24 studies with 2,507 CPPs exposed for a calculated abuse/addiction rate of 3.27%. Within this grouping for those studies that had preselected CPPs for COAT exposure for no previous or current history of abuse/addiction, the percentage of abuse/addiction was calculated at 0.19%. For the ADRB grouping, there were 17 studies with 2,466 CPPs exposed and a calculated ADRB rate of 11.5%. Within this grouping for preselected CPPs (as above), the percentage of ADRBs was calculated at 0.59%. In the urine toxicology grouping, there were five studies (15,442 CPPs exposed). Here, 20.4% of the CPPs had no prescribed opioid in urine and/or a nonprescribed opioid in urine. For five studies (1,965 CPPs exposed), illicit drugs were found in 14.5%. The results of this evidence-based structured review indicate that COAT exposure will lead to abuse/addiction in a small percentage of CPPs, but a larger percentage will demonstrate ADRBs and illicit drug use. These percentages appear to be much less if CPPs are preselected for the absence of a current or past history of alcohol/illicit drug use or abuse/addiction.Pain Medicine 01/2008; 9(4):444-59. · 2.46 Impact Factor
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ABSTRACT: background The available drugs to treat neuropathic pain have incomplete efficacy and dose-limit- ing adverse effects. We compared the efficacy of a combination of gabapentin and mor- phine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia. methods In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine — each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients re- ceiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated dos- es, mood, and quality of life. abstractNew England Journal of Medicine 07/2005; 352(25):2650-1; author reply 2650-1. · 51.66 Impact Factor
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ABSTRACT: Chronic 'pathological' pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular determinants of nociceptive sensitization are natural targets for potential analgesic drugs used in the treatment of different forms of pain. Most of these determinants are common to all forms of chronic pain, and it is therefore not surprising that drugs specifically targeted for the treatment of neuropathic pain are effective in relieving nociceptive inflammatory pain and vice versa. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs, i.e. drugs that are able to discriminate between 'normal' and 'pathological' pain transmission. Among these, pregabalin and gabapentin bind to the alpha(2)delta subunit of voltage-sensitive Ca2+ channels, which sustain the enhanced release of pain transmitters at the synapses between primary afferent fibres and second-order sensory neurons under conditions of chronic pain. Pregabalin in particular represents a remarkable example of a context-dependent analgesic drug that acts at a critical step of nociceptive sensitization. Preclinical and clinical data suggest that pregabalin is more than a structural and functional analogue of gabapentin and may be effective in the treatment of nociceptive inflammatory pain that is resistant to gabapentin.Clinical Drug Investigation 02/2009; 29(3):203-13. · 1.92 Impact Factor