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Non-opioid analgesics: other
56
Abstracts
(789) Levetiracetam as an adjunct to other AED‘s in the treatment of stable, satisfied, chronic pain
(791) Improved mobility in intractable pain patients treated with zonisamide
M. Kaplan, L. Kaplan; The Rehabilitation Team, Baltimore, MD There exists a large patient population with stable, minimally satisfied chronic pain and anxiety issues which could benefit from treatments that could increase quality of life. We have found the GABA effect of levetiracetam a beneficial adjunct therapy in a subgroup of chronic pain patients. Recent publications showed that changes in GABA neurotransmission in descrete areas of the cerebral cortex can raise or lower the pain threshold-producing analgesia or hyperalgesia. The objective of this study was to determine the additional effect of stimulating GABA pathways by adding levetiracetam to other GABA agonists. Levetiracetam was added to an existing medication profile (which included a GABA agent) to patients (n⫽53) previously experiencing stable and adequate control of their pain with AED and breakthrough pain medications with various chronic pain syndromes, including neuropathic pain, radiculopathies, and headaches. We hypothesized that as anxiety and pain are abnormal patterns of neuronal activity, levetiracetam will have a marked effect against anxiety as well as acute and chronic pain occurrences. After treatment with levetiracetam, all patients with diabetic neuropathy reported improvements in pain, 86% had improvements in radiculopathy alone, and 76% of patients reported improvement in chronic headaches. Approximately 80% of the patients who continued levetiracetam experienced good or better improvement in their stable chronic pain management after the addition of levetiracetam. Approximately 50% of patients had good or better improvements in sleep, and self reported anxiety levels improved in all patients. Dosages ranging 750 - 1500 mg were tolerated by 90% of patients yielding significant improvements in both pain and anxiety. The findings of this clinical trial with levetiracetam support that the agent is an efficacious and well tolerated treatment as an add on adjunctive therapy for stable chronic pain and anxiety. In addition, levetiracetam may exert several atypical actions on GABA and glycine-gated currents.
A. Dubin, H. Smith; Albany Medical College, Albany, NY Two patients were treated for intractable pain secondary to work-related injuries. The first patient, a 48-year-old female, presented in November 1993 with neck pain due to soft tissue myofascial pain, arm pain due to a brachial plexus stretch injury, and clinical depression. Pain management was complicated by a long history of atypical depression. The second patient, a 45-year-old male, was diagnosed in February 1996 with pain due to brachial plexopathy, and subsequently developed depression. Despite administration of multiple antiepileptic drugs (AEDs), antidepressants, and analgesics (including opioids), the pain remained uncontrolled in both patients. Zonisamide (Zonegran®, Elan Pharmaceuticals), a synthetic sulfonamide derivative, is approved as adjunctive therapy for the treatment of patients with partial seizures. Zonisamide (100 mg daily) was administered to each of the patients described because of its potential efficacy in patients with intractable pain, the ability to dose once daily due to a long half-life (t1⁄2 ⫽ 63 hr) which may improve compliance, and the relatively low number of drug-drug interactions. Both patients achieved sustained substantial improvement in pain control, including taking fewer medications for pain and improved activity levels. Patient 1 experienced a sustained improvement in mood, psychiatric condition, and depression, and increased function in daily activities. Patient 2 experienced improved ability to resume light carpentry and other light repair work. Additionally, his work tolerance increased from 1 to 4 hrs/day. Zonisamide may be a good choice for patients with intractable neuropathic pain, particularly those who are receiving multiple medications for comorbidities. Zonisamide is thought to have multiple mechanisms of action, which may benefit more patient types than AEDs with a single mechanism of action. The possible mechanisms of action will be discussed.
(790) The use of intraarticular clonidine for the management of complex regional pain syndrome of the knee
(792) Efficacy and tolerability of oxcarbazepine in patients with painful neuropathic pain
A. Harpavat, S. Reuben; Baystate Medical Center, Springfield, MA CRPS of the knee is poorly understood and difficult to treat. We have previously reported the efficacy of IVRA with clonidine for CRPS of the knee (J Clin Anesth 2002). Intraarticular (IA) clonidine has proven to be an effective analgesic when administered for arthroscopic knee surgery (Anesth Analg 1999) and may contribute to a decreased incidence of CRPS following ACL surgery (Reg Anesth Pain Med 2002). We report the efficacy of IA clonidine in the management of CRPS of the knee. A 22-year old 60 kg female complained of burning pain (VAS ⫽ 9) over the anterior aspect of the knee, joint stiffness and diffuse hyperesthesia after blunt trauma to the knee. Examination revealed tenderness over the patellofemoral joint, mottling of the skin over the anterior knee, decreased ROM, and decreased temperature (1.3° C) compared to the contralateral extremity. Physical therapy, NSAIDs, and TCAs provided no improvement. An IA injection of 30 mL 0.25% bupivacaine and 60 g clonidine was performed each week for 6 consecutive weeks. The first IA injection resulted in complete pain relief for 2 days after which the pain gradually returned to a lower intensity (VAS ⫽ 6). She also noticed a reduction in the stiffness and color changes of the affected extremity. A second IA injection provided 6 days of pain relief after which the pain returned to a lower intensity (VAS ⫽ 3). Three more successive IA blocks with clonidine were performed on consecutive weeks resulting in complete resolution of her CRPS symptoms. The patient has remained painfree for 6 months after the last treatment. IA clonidine may be beneficial in the treatment of CRPS of the knee.
P. Magenta, S. Arghetti, F. Massimo, A. Levati, S. Vesconi; Niguarda Ca’ Granda Hospital, Milan - Italy The objective of this study was to evaluate the efficacy, and tolerability of oxcarbazepine in the treatment of neuropathic pain. This was an open-label, twenty-week trial, consisting of a one-week prospective Screening Phase followed by a three-month Treatment Phase. Treatment with oxcarbazepine was initiated at 300 mg/day and the daily dose was doubled on 3 days basis and titrated to tolerability over one-three weeks, up to 1800 mg/day. This was followed by a three-month fixeddose Maintenance Phase during which patients were maintained on oxcarbazepine at a mean dose of 1.200 mg/day or highest tolerated dose. The patients underwent a follow up period (from 1 month to 18 months). The primary efficacy variable was the change in the pain rating assessed on the VAS between the Screening Phase and the Treatment Phase. All analysis were performed on the intent-to-treat population. Thirty-seven patients were enrolled in the trial:19 female, and18 male, mean age 61.54 years. All patients suffered from neuropathic pain due to different origins: disk herniation in 22 patients, spinal stenosis in 6 cases, vascular disease in 4 cases, coccygodynia in 3 cases, and spinal cord trauma.The mean daily oxcarbazepine dose during the Maintenance Phase was 1.378 mg. The mean VAS score dropped from 8.95 during the Screening Phase to 5.84 after 3 months on OXC (p⬍0.0001), and to 5.00 at the end of the trial (p⬍0.001), for a mean reduction of 34.75% at 3 months, and of 44.13% at the end of the follow up. Oxcarbazepine was well tolerated with the most common adverse events consisting of transient nausea, headache, and dizziness. The results suggest that oxcarbazepine administered as monotherapy is an efficacious and safe option for the symptomatic treatment of pain associated with painful neuropathic conditions. These results will need to be confirmed in large, double-blind, placebo controlled, randomized clinical trials.
Abstracts
(789) Levetiracetam as an adjunct to other AED‘s in the treatment of stable, satisfied, chronic pain
(791) Improved mobility in intractable pain patients treated with zonisamide
M. Kaplan, L. Kaplan; The Rehabilitation Team, Baltimore, MD There exists a large patient population with stable, minimally satisfied chronic pain and anxiety issues which could benefit from treatments that could increase quality of life. We have found the GABA effect of levetiracetam a beneficial adjunct therapy in a subgroup of chronic pain patients. Recent publications showed that changes in GABA neurotransmission in descrete areas of the cerebral cortex can raise or lower the pain threshold-producing analgesia or hyperalgesia. The objective of this study was to determine the additional effect of stimulating GABA pathways by adding levetiracetam to other GABA agonists. Levetiracetam was added to an existing medication profile (which included a GABA agent) to patients (n⫽53) previously experiencing stable and adequate control of their pain with AED and breakthrough pain medications with various chronic pain syndromes, including neuropathic pain, radiculopathies, and headaches. We hypothesized that as anxiety and pain are abnormal patterns of neuronal activity, levetiracetam will have a marked effect against anxiety as well as acute and chronic pain occurrences. After treatment with levetiracetam, all patients with diabetic neuropathy reported improvements in pain, 86% had improvements in radiculopathy alone, and 76% of patients reported improvement in chronic headaches. Approximately 80% of the patients who continued levetiracetam experienced good or better improvement in their stable chronic pain management after the addition of levetiracetam. Approximately 50% of patients had good or better improvements in sleep, and self reported anxiety levels improved in all patients. Dosages ranging 750 - 1500 mg were tolerated by 90% of patients yielding significant improvements in both pain and anxiety. The findings of this clinical trial with levetiracetam support that the agent is an efficacious and well tolerated treatment as an add on adjunctive therapy for stable chronic pain and anxiety. In addition, levetiracetam may exert several atypical actions on GABA and glycine-gated currents.
A. Dubin, H. Smith; Albany Medical College, Albany, NY Two patients were treated for intractable pain secondary to work-related injuries. The first patient, a 48-year-old female, presented in November 1993 with neck pain due to soft tissue myofascial pain, arm pain due to a brachial plexus stretch injury, and clinical depression. Pain management was complicated by a long history of atypical depression. The second patient, a 45-year-old male, was diagnosed in February 1996 with pain due to brachial plexopathy, and subsequently developed depression. Despite administration of multiple antiepileptic drugs (AEDs), antidepressants, and analgesics (including opioids), the pain remained uncontrolled in both patients. Zonisamide (Zonegran®, Elan Pharmaceuticals), a synthetic sulfonamide derivative, is approved as adjunctive therapy for the treatment of patients with partial seizures. Zonisamide (100 mg daily) was administered to each of the patients described because of its potential efficacy in patients with intractable pain, the ability to dose once daily due to a long half-life (t1⁄2 ⫽ 63 hr) which may improve compliance, and the relatively low number of drug-drug interactions. Both patients achieved sustained substantial improvement in pain control, including taking fewer medications for pain and improved activity levels. Patient 1 experienced a sustained improvement in mood, psychiatric condition, and depression, and increased function in daily activities. Patient 2 experienced improved ability to resume light carpentry and other light repair work. Additionally, his work tolerance increased from 1 to 4 hrs/day. Zonisamide may be a good choice for patients with intractable neuropathic pain, particularly those who are receiving multiple medications for comorbidities. Zonisamide is thought to have multiple mechanisms of action, which may benefit more patient types than AEDs with a single mechanism of action. The possible mechanisms of action will be discussed.
(790) The use of intraarticular clonidine for the management of complex regional pain syndrome of the knee
(792) Efficacy and tolerability of oxcarbazepine in patients with painful neuropathic pain
A. Harpavat, S. Reuben; Baystate Medical Center, Springfield, MA CRPS of the knee is poorly understood and difficult to treat. We have previously reported the efficacy of IVRA with clonidine for CRPS of the knee (J Clin Anesth 2002). Intraarticular (IA) clonidine has proven to be an effective analgesic when administered for arthroscopic knee surgery (Anesth Analg 1999) and may contribute to a decreased incidence of CRPS following ACL surgery (Reg Anesth Pain Med 2002). We report the efficacy of IA clonidine in the management of CRPS of the knee. A 22-year old 60 kg female complained of burning pain (VAS ⫽ 9) over the anterior aspect of the knee, joint stiffness and diffuse hyperesthesia after blunt trauma to the knee. Examination revealed tenderness over the patellofemoral joint, mottling of the skin over the anterior knee, decreased ROM, and decreased temperature (1.3° C) compared to the contralateral extremity. Physical therapy, NSAIDs, and TCAs provided no improvement. An IA injection of 30 mL 0.25% bupivacaine and 60 g clonidine was performed each week for 6 consecutive weeks. The first IA injection resulted in complete pain relief for 2 days after which the pain gradually returned to a lower intensity (VAS ⫽ 6). She also noticed a reduction in the stiffness and color changes of the affected extremity. A second IA injection provided 6 days of pain relief after which the pain returned to a lower intensity (VAS ⫽ 3). Three more successive IA blocks with clonidine were performed on consecutive weeks resulting in complete resolution of her CRPS symptoms. The patient has remained painfree for 6 months after the last treatment. IA clonidine may be beneficial in the treatment of CRPS of the knee.
P. Magenta, S. Arghetti, F. Massimo, A. Levati, S. Vesconi; Niguarda Ca’ Granda Hospital, Milan - Italy The objective of this study was to evaluate the efficacy, and tolerability of oxcarbazepine in the treatment of neuropathic pain. This was an open-label, twenty-week trial, consisting of a one-week prospective Screening Phase followed by a three-month Treatment Phase. Treatment with oxcarbazepine was initiated at 300 mg/day and the daily dose was doubled on 3 days basis and titrated to tolerability over one-three weeks, up to 1800 mg/day. This was followed by a three-month fixeddose Maintenance Phase during which patients were maintained on oxcarbazepine at a mean dose of 1.200 mg/day or highest tolerated dose. The patients underwent a follow up period (from 1 month to 18 months). The primary efficacy variable was the change in the pain rating assessed on the VAS between the Screening Phase and the Treatment Phase. All analysis were performed on the intent-to-treat population. Thirty-seven patients were enrolled in the trial:19 female, and18 male, mean age 61.54 years. All patients suffered from neuropathic pain due to different origins: disk herniation in 22 patients, spinal stenosis in 6 cases, vascular disease in 4 cases, coccygodynia in 3 cases, and spinal cord trauma.The mean daily oxcarbazepine dose during the Maintenance Phase was 1.378 mg. The mean VAS score dropped from 8.95 during the Screening Phase to 5.84 after 3 months on OXC (p⬍0.0001), and to 5.00 at the end of the trial (p⬍0.001), for a mean reduction of 34.75% at 3 months, and of 44.13% at the end of the follow up. Oxcarbazepine was well tolerated with the most common adverse events consisting of transient nausea, headache, and dizziness. The results suggest that oxcarbazepine administered as monotherapy is an efficacious and safe option for the symptomatic treatment of pain associated with painful neuropathic conditions. These results will need to be confirmed in large, double-blind, placebo controlled, randomized clinical trials.