ABAPENTIN FOR PAINFUL HIV NEUROPATHY BLINDED, RANDOMIZED TRIAL
COMPARING HIGH AND LOW DOSES
M.C. Rowbotham, C. Diamond, McCoy, J. Brown, S. Twilling, L. Sacks, G. Young, Pain Clinical Research Center, UCSF, San Francisco, CA
AIM OF INVESTIGATION: Double-blind, multi-center trial of gabapentin for painful neuropathy associated with HIV infection.
METHODS: Adult HIV-positive patients with painful polyneuropathy were randomized to 4 weeks therapy with either low (900 mg/day) or high (3,600 mg/day) dose gabapentin (GBP). Evaluations included daily diary pain and sleep ratings, SF-MPQ, POMS, SF-36 Quality of Life, Multidimensional Pain Inventory, and Global Impression of Change ratings. Data analysis for daily diary pain ratings was conducted on an intent to treat sample (ITT) and an efficacy-evaluable sample (EE) who completed the entire study.
RESULTS: Sixty-five subjects formed the ITT sample. Subjects on low dose GBP reported a 28% reduction in pain compared to 41% reduction with high dose GBP (p=.12). In the EE sample (n=58), pain declined by 30% with low dose GBP and 46% with high dose GBP (p=.04). Secondary measures showed numerical advantages with high dose GBP, but none reached statistical significance.
CONCLUSIONS: Pain declined during 4 weeks of gabapentin therapy at both 900 and 3600 mg/day. Secondary measures also favored high dose gabapentin, but more subjects discontinued the study due to adverse effects. High dose gabapentin provided superior pain reduction in subjects who completed the trial. Gabapentin has an acceptable side effect profile and minimal drug-drug interactions, features especially important for HIV-infected individuals utilizing complex anti-retroviral treatment regimens.
ACKNOWLEDGMENTS: Supported by an external research grant from Parke-Davis Pharmaceuticals/Pfizer Inc. Dr. Rowbotham has been a consultant to and received grant support from the sponsor. Carey Aron worked for Parke-Davis during the time of the study.
TOPIRAMATE IN THE TREATMENT OF CHRONIC SCIATICA
S. Khoromi, M.B. Cahill, K. Parada, S., Pain and Neurosensory Mechanisms Branch, NIDCR, Bethesda, MD
Aim of investigation: To assess the efficacy of topiramate in the treatment of chronic lumbar radicular pain, a common syndrome which has been the subject of few randomized drug trials.
Methods: A double-blind, randomized, 2-period, crossover, placebo-controlled study of topiramate (TOP), 50-400 mg, and the "active placebo" (PL), diphenhydramine, 6.25-50 mg, in the treatment of chronic sciatica. Patients were 18 to 75 yrs old with chronic leg or back pain of at least moderate severity for 3 months, with pain radiating below the knee and/or motor or sensory loss in the distribution of L5/S1roots on the side of pain. Each treatment period consisted of 5 weeks titration, 2 weeks of maintenance at the maximal titrated dose, and 2 weeks of drug taper. Back and leg pain were rated daily on a scale of 0 to 10.
Results: As of 01/01/02, 31 pts had entered the study. The 23 evaluable pts included 18 completers and 5 others who completed one treatment and rated pain during at least 3 days of drug treatment in the other. Median doses were: TOP, 200 mg, and PL, 50 mg. Mean ratings of back pain were: baseline (BL) 4.9, PL 4.0, and TOP 3.5; and for leg pain scores were: BL 4.3, PL 3.2, and TOP 2.9. With TOP, mean reduction was 13% for back pain (95% CI, 7% worse to 33% improved) and 10% for leg pain (95%CI, 23% worse to 44% improved. Neither result approached statistical significance.
8 subjects dropped out due to topiramate side effects which included dizziness and sedation (3 pts), distal paresthesias (3 pts), dysgeusia and weight loss (2 pts), irritability and depression (2 pts), and fatigue (2 pts).
Conclusion: The interim analysis suggests that topiramate has, at best, modest efficacy and substantial side effects in patients with chronic sciatica.
Acknowledgments: Supported by NIDCR grant ZO1 DE00366
GABAPENTIN IN THE TREATMENT OF NEUROPATHIC PAIN
P. Sevcik, J. Mastik, Anaesthesiology and Intensive Care, St. Anns Hospital, Brno, Czech Republic, Neurology, St. Anns Hospital, Brno, Czech Republic, Gabapentin for the treatment of neurogenic pain
Aim of Investigation: Verification of gabapentin efficacy and adverse effects in the treatment of chronic neurogenic pain.
Methods: Patients with different types of neurogenic pain were monitored prospectively for a six-month period according to the protocol, between December 1999 and March 2001. Pain intensity was monitored by visual analogue scale (VAS 0-10) three times a day before start of therapy, after 1 and 2 weeks, 1, 3 and 6 months. Over the same intervals, we also monitored gabapentin dosage, concomitant medication, adverse effects, evaluation of treatment by patients, and reasons for potential premature treatment withdrawal.
Results: Forty six patients entered the study. Monitoring was completed in 21 women and 13 men with an average age of 56 (range 34-90) years, and median pain duration of 40 (range 3442) months before the treatment. Twelve patients failed to complete the treatment. The average maximum daily dose of gabapentin was 1231 mg and the average maintenance dose was 962 mg. Average VAS before start of therapy was 7.3, after 2-week treatment 4.9, after 3 months 3.6, after 6 months 3.4. Adverse effects occurred in 22 subjects (65 %), however, these were mild for 18 of the subjects (including sedation, somnolence, dizziness). Only 4 subjects experienced moderate adverse effects (diarrhoea, epigastrial tension, somnolence). No significant changes in concomitant treatment during the study were observed.
Conclusions: Gabapentin notably enlarged treatment options for different types of neurogenic pain with acceptable incidence and severity of adverse effects.
Acknowledgments: Supported by grant from the Czech Pain Society.
LAMOTRIGINE PLASMA LEVELS IN SEVERE NEUROPATHIC PAIN
J.E. Devulder, Ansesthesia, Ghent University Hospital, Ghent, Belgium
Aim of the investigation: To evaluate plasma concentrations and side effects in chronic pain patients using high doses of lamotrigine.
Methods: In our department lamotrigine is only used for severe neuropathic pain if sodiumvalproate or carbamazepine are ineffective. In some patients with the failed back surgery syndrome(mixed nociceptive-neuropathic pain)high doses of lamotrigine are needed to obtain pain relief. We monitored the lamotrigine plasma levels of 6 patients with severe neuropathic pain (VAS>7/10) with the High Performance Liquid Chromatographic Technique. In those patients no concomitant medication was used and lamotrigine was administered in a twice daily regimen. Plasma levels were determined 12 hours after the last oral lamotrigine intake.
Results: 3 patients used lamotrigine for facial deafferentiation pain (1patient had a daily intake of 300 mg and 2 patients 400 mg);3 patients with the failed back surgery syndrome needed 800 mg lamotrigine daily for severe neuropathic pain in the legs. The plasma levels are consecutively: 18,37 mol/l;27,64 mol/l and 25,8 mol/l for the deafferentation patients and 32,45 mol/l;40,27 mol/l and 43,79 mol/l for the failed back patients.
Conclusions: 3 patients treated with a high oral lamotrigine dose (800 mg daily) obtained plasma levels around 40 mol/l which are rather high. Clinical anticonvulsant concentrations are mostly about 4-16 mol/l. However,some epilepsy patients also need plasma concentrations up to 40 mol/l. High plasma concentrations (>25 mol/l) influence sodium, calcium and potassium currents probably explaining the pain relief mechanisms. No side effects or complications were noticed and more than 50 % pain relief could be obtained.
Acknowledgement: Supported by grants of Glaxosmithkline Belgium
GABAPENTIN IN COMPLEX REGIONAL PAIN SYNDROME: A RANDOMIZED, DOUBLE-BLIND, CROSSOVER
D. Hartmann, M. Baird, A. Souter, Pain Clinic, Ninewells Hospital and Medical School, Scotland, United Kingdom , Pain Clinic, Royal United Hospital, Bath, United Kingdom
AIM OF INVESTIGATION: To determine the analgesic effect of Gabapentin in patients with Complex Regional Pain Syndrome (CRPS) and establish the feasibility of using a randomised, double-blind, crossover methodology.
METHODS: Fourteen patients with CRPS Type I (n=12)and Type II (n=2) (according to IASP diagnostic criteria) attending a pain clinic agreed to participate in the study. Duration of disease was 1-20 years (mean = 6.7). Following written consent, patients were randomised to receive either placebo or active drug for a 5 week period followed by a two week washout period and a further five weeks of the alternate treatment. Outcome measures included: McGill Pain Questionnaire-SF, Neuropathic Pain Scale, 10cm VAS, and Global Impression of Change Scale (GIC) at baseline, pre and post washout and following completion of treatment. A daily pain diary was also completed throughout the duration of the trial.
RESULTS: Eleven patients completed the trial. Dropouts were due to minor side-effects i.e., headache and nausea. There was an insignificant trend towards lower VAS scores in the active group throughout the trial. Using GIC eight patients reported no change during active treatment, two minimal change and one patient was very much improved on Gabapentin.
CONCLUSIONS: Feasibility of the trial methodology was established. There were no significant differences in pain or change scores due to active treatment. Benefits of gabapentin were found in a subset of participants . A large multi-centre study would be needed to determine the true treatment effect of Gabapentin in CRPS.
ACKNOWLEDGEMENTS: This study was financed by an educational grant from Parke Davis
AS A TREATMENT OPTION FOR PHANTOM LIMB PAIN
J.E. Triebel1, N.L. Luppa, W.L. Physical Medicine and Rehabilitation, Rehabiltation Clinic of Suva, Switzerland, pain unit, Bellikon, Switzerland
AIM OF THE INVESTIGATION: Observation of the clinical course of amputees with phantom limb pain under the medication of Neurontin (Gabapentin)
METHODS: 20 amputees with phantom limb pain over VAS 5 (on a scale from 0-10) were enrolled into the study. It was an open label study with a weekly follow up for 12 weeks. Intensity of pain (on VAS-scale) and quality of sleep were measured by regular telephone interviews, visits and by a patient diary.
Additionally the Clinical and Patient Global Impression of Change (CGIC and PGIC) and the Short Form McGill Pain Questionnaire (SF-MPQ) were monitored on a regular basis.
RESULTS: A significant pain reduction within the 12 weeks of treatment was observed. The mean weekly pain score (VAS 0-10) decreased from 7.5 to 4.3. The current pain intensity decreased from 7.0 to 4.2. The results were statistically highly significant.
CONCLUSIONS: A clinically relevant reduction of pain under the medication of Neurontin (Gabapentin) was observed. Even in patients with long term phantom limb pain a pain reducing impact seems to be possible.
The spectrum of side effects (most often observed were: dizziness, drowsiness and diplopia) was within tolerable limits. In view of the difficulties observed in the treatment of phantom limb pain this study may speak in favor of a new pharmacological treatment option in phantom limb pain.
ACKNOLEDGEMENTS: We thank Suva Switzerland and Pfizer Switzerland for their support.
THE PRACTICAL DOSING AND TITRATION OF GABAPENTIN FOR OPTIMUM EFFICIENCY AND
TOLERABILITY IN TREATING NEUROPATHIC PAIN: ANALYSIS OF FOUR RANDOMIZED, PLACEBO-CONTROLLED
M. Backonja, Department of Neurology, University of Wisconsin Medical School, Madison, WI
AIM OF INVESTIGATION: To identify gabapentin dosing regimens that optimize efficacy and tolerability in treating neuropathic pain, and formulate practical dosing and titration guidelines.
METHODS: Four recent randomized, placebo-controlled trials of gabapentin were examined to interpret the relationship between efficacy and tolerability. Subjects (n=1033) treated various neuropathic pain syndromes with gabapentin or placebo. Gabapentin was initiated at 300 mg/day increasing to 900 mg/day over the first 3 days, then titrated to between 900 - 3600 mg/day. Where tolerated, maximum dosage was maintained for 4 weeks. Primary efficacy was measured by evaluating change in average daily pain scores by an 11-point Likert scale against baseline.
RESULTS: Gabapentin dramatically improved average daily pain scores when doses of 1800 mg/day or higher were achieved. In general, greater differences were observed with continued titration over time. Significant efficacy in relief of neuropathic pain with gabapentin was observed within 12 weeks, starting at doses between 900 and 1200 mg/day. In general, adverse effects were mild to moderate, with no differences observed at higher doses. Where examined, QoL measures of bodily function, vitality, and mental health were significantly improved with gabapentin.
CONCLUSIONS: Gabapentin doses up to 3600 mg/day are safe and efficacious in treating neuropathic pain. After initiation to 900 mg/day over 3 days, titration to 1800 mg/day is recommended. If required, gabapentin can be further titrated to 3600 mg/day within 4 weeks. Maintenance doses of 18003600 mg/day are recommended depending upon patient tolerability.
ACKNOWLEDGMENTS: This study was supported by Pfizer, Inc.
STUDY OF GABAPENTIN AND CLOMIPRAMINE USE FOR CHRONIC PAIN MANAGEMENT IN SPINAL CORD
P.E. Rebolledolez, P. Valenzuela, F. Larraguibel, A. Mujica, Department of Mental Health, Asociacin Chilena de Seguridad, Santiago, Chile
Aim of Investigation: To determine prevalence of pain in spine cord injury patients and evaluate the effectiveness of gabapentin and clomipramine for chronic pain management in these patients.
Methods: Our investigation was performed in Hospital del Trabajador in 45 injured workers from Metropolitan Area with spinal cord injury between January and May 2001. Pain patients underwent randomized, double blind and comparative 8 weeks study with increasing dosis of gabapentin (400-1600 mg) and clomipramine (25-100 mg). Systemic evaluation was conducted using VAS and UKU Side Effects Rating Scale (Baseline, 2, 4, 6 and 8 weeks). Before and after the treatment the following measures were taken: Goldberg Health Questionaire-30, Hamilton Anxiety and Depression Scale.
Results: The prevalence of pain in spinal cord injury patients was 77.8%. 35 patients were in pain. 37% completed the study, 31% dropped out due to side effects, 6% were excluded and 26% did not participate. Both, gabapentine and clomipramine reduced intensity of pain in 48% and 55% respectively (p=0.767), but the dropped out due to side effects was higher in clomipramine group. Frequent side effects were nausea and vomiting for clomipramine group and somnolence for gabapentine group. Measures of anxiety and depression were reduced after the treatment in both groups.
Conclusions: Both, gabapentine and clomipramine reduced intensity of pain and measures of anxiety and depression but gabapentine was better tolerated in this kind of patients.
Acknowledgments: Supported by Asociacin Chilena de Seguridad, Laboratorios Chile y Parke-Davis.
GABAPENTINE FOR ATTENUATION OF PAIN FOLLOWING RAPID OPIATE DETOXIFICATION (ROD)
L. Partecke, L. Latasch,, Dep. of Anesthesia and Pain Therapy, Nordwest Hospital, Frankfurt/Main, Germany , Dep. of Anesthesia, Jewish Hospital Berlin, Berlin, Germany , Clinics of Vascular Surgery, University of Dsseldorf, Dьsseldorf, Germany
Aim of Investigation: Following ROD, patients often complain of intense back pain and restless leg syndrome (RLS). These do not respond to NSARs or serotonine precursor treatment respectively.
Therefore Gabapentine (GABA)(antihyperalgesic and sedative properties) was used whenever patients experienced RLS, thrashing, and/or back pain in the ICU.
Methods: Following informed consent, 21 patients (heroin or methadone maintenance), underwent ROD using naltrexone and simultaneous administration of clonidine and somatostatin. Aside from amplitude height of late SEP's (SSEPs; > 100 ms), individual tolerance to an increase in electrical stimuli (mA) to the forearm was measured at following end-points: awake, during anesthesia, before/after a total dose of 1200 mg of GABA.
Data was analyzed using Friedman's test for repeated measures of variance on ranks, and the Student-Newman-Keuls test for multiple comparison.
Results: Following ROD, amplitude in the SSEP increased sign. to control (8.4 2.5 to 12.3 3.3 V; p < 0.01) which dropped below control (3.5 1.5 V; p < 0.01) after GABA. Simultaneously tolerance to electrical stimuli decreased from 10.2 1.2 mA to 4.4 1.2 mA. After GABA, tolerance increased to 19.5 4.8 mA. There was a close inverse linear correlation of amplitude height of SSEP and tolerance to electrical stimuli (r2 = 0.88). Inverse linear correlation of tolerance to electrical stimuli and latency (ms) of SSEP was less (r2 = 0.61).
Conclusions: Post detox. withdrawal symptoms with pain, can be blunted sufficiently with GABA which has a wide margin of safety and favorable depressive effect on neuronal excitatory transmission.
LAMOTRIGINE EFFECTIVENESS FOR REFRACTORY NEUROPATHIC PAIN
M.R. Semenchuk, G. Gregory, Clinical Development & Medical Affairs, GlaxoSmithKline, Tucson, AZ , Neurology, Nevada Neurological Consultants, Ltd., Las Vegas, NV
AIM OF INVESTIGATION: To evaluate the effectiveness and safety of lamotrigine for the treatment of refractory neuropathic pain.
METHODS: A retrospective chart review of patients treated with lamotrigine as third line therapy for various neuropathic pain syndromes refractory to conventional therapies.
RESULTS: Eighty patients were treated with lamotrigine. Diagnoses included atypical facial pain (4), central pain (4), diabetic neuropathy (5), failed back syndrome (2), post-herpetic neuralgia (4), nonspecific peripheral neuropathy (27), radiculopathy (11), trigeminal neuralgia (19), other (4). For all of these indications lamotrigine was used as third line therapy. Patients were refractory to gabapentin, tricyclic antidepressants, narcotics, carbamazepine, oxcarbazepine, and topiramate. Twelve patients had no follow-up. Of the remainder, 38% experienced clear improvement and continued on lamotrigine treatment. The response rate was highest in diabetic neuropathy (80%), peripheral neuropathy (48%), and trigeminal neuralgia (42%). Of the 11 pts with radiculopathy, only one experienced improvement. Effective doses ranged from 50-575 mg/day. Side effects included nonserious rash (2), lethargy (2), headache (1), confusion (1), dizziness (1), GI upset (1)
CONCLUSION: In this population of refractory pain patients, lamotrigine was particularly useful in trigeminal neuralgia and peripheral neuropathy, diabetic and otherwise, and did poorly in radiculopathy. Large scale placebo controlled multicenter studies are needed to further explore the role of lamotrigine in the treatment of neuropathic pain.
ACKNOWLEDGEMENT: GlaxoSmithKline for poster development.
VALPROIC ACID IN PAINFUL POLYNEUROPATHY
M. Otto, F.W. Bach, T.S. Jensen, K. Brosen, S.H. Sindrup, Neurology, Odense University Hospital, Odense C, Denmark , Neurology, Aarhus University Hospital, Aarhus C, Denmark , Clinical Pharmacology, University of Southern Denmark, Odense C, Denmark
Aim of investigation: The mainstay of treatment of pain in polyneuropathy is tricyclic antidepressants and some anticonvulsants. In a substantial number of patients, the tricyclic antidepressants cannot be used either due to contraindications or intolerable side effects and the anticonvulsants tested until now are somewhat less efficacious. Valproic acid is an anticonvulsant with multiple pharmacological actions that may interfere with pain processing. It has not previously been tried in painful polyneuropathy. The aim of this study was to test if valproic acid relieves painful polyneuropathy.
Methods: We have included 37 patients with painful polyneuropathy in a randomised, double-blind, cross-over trial of 4 plus 4 weeks with valproic acid 1500 mg daily against placebo. The main outcome measures are the median value of patients daily ratings by numeric rating scales (0-10 points) of total pain (primary outcome measure), pain paroxysms, steady deep pain, steady superficial burning pain, touch-evoked pain and pressure-evoked pain during the last week of each treatment period. Further, overall pain relief is recorded.
Results: So far, 30 patients have completed the study, 2 have dropped out and 5 are still in the trial.
Conclusions: The study is closed for inclusion and the primary results will be presented.
Acknowledgement: Desitin Pharma GmbH, Germany, provided study medication.
LAMOTRIGINE FOR GABAPENTIN RESISTANT NEUROPATHIC PAIN
V. Whizar,-Lugo C., Estrada-Coronado, R. Cisneros-Corral, Servicios Profesionales de Anestesiologia y Clinica de Dolor, Centro Medico del Noroeste, Tijuana, Mexico
AIM OF INVESTIGATION: To study the useful of crescendo doses of lamotrigine in patients with diverse forms of neuropathic pain non-responding to gabapentin.
METHODS: Twenty-five patients with severe neuropathic pain, who were taking gabapentin 1200 up to 2400 mg daily, received crescendo dose of lamotrigine starting at 25 mg twice a day. All cases were monitored weekly at the office, until good pain relieve was achieved (VAS 5 or more), followed by telephone calls/office visits every week until end of follow-up. The dose increments were based on pain response and side effects. As soon as the patient report 50% of pain improvement, gabapentin was slowly reduced until discontinued.
RESULTS: All but two patients were able to finish the study. Adequate pain relief was obtained in 17 patients. Six cases did not respond or had severe lamotrigine side effects. Twelve out of 23 patients were able to stop gabapentin, and 11 cases remained on gabapentin patients can be treated either by slowly switching gabapentin to lamotrigin or by using both drugs+lamotrigine. In this last group only 5 patients had significant pain improvement.
CONCLUSIONS: Gabapentin non-responding neuropathic pain
RECTAL ANTICONVULSANT DRUGS: AN ALTERNATIVE ROUTE FOR SEVERE TRIGEMINAL PAIN. A CASE
T. Figueroa-Garcia, V.M. Whizar-Lugo, J. Godines-Velasquez, E. Reyes-Aveleyra, M.A., Servicios Profesionales de Anestesiologia y Clinica de Dolor, Centro Medico del Noroeste, Tijuana, Mexico
AIM OF INVESTIGATION: To determine if rectal administration of antiepileptics drugs have a role in the treatment of trigeminal pain in a patient unable to take oral medicines.
Case. An 80 years old patient with severe trigeminal pain due to a basilar artery dolichoectasia, was unable to take oral medication to control his symptom, and refused to have a nasogastric tube to administer his medicines. Intravenous phenytoin, followed by intravenous lidocaine drip, and i.v. tramadol failed to release his pain. As a desperate approach, we use a mixture of carbamazepine 400 mg, gabapentine 400 mg, baclofen 20 mg every six hours given by rectal enema, and IV phenytoin 100 mg every 8 h.
RESULTS: After the second rectal enema, the patient pain intensity went down dramatically. Three days later, he was able to take oral anticonvulsants to continue his treatment. After the second enema, plasma levels of carbamazepine were 6.5 g/mL (4-10), gabapentine 0.5 g/mL (2-20), and baclofen 0 (0.08-0.40). Phenytoin plasma levels (after IV administration every 8 h) were 6.5 g/mL (4-10)
CONCLUSIONS: Although plasma levels of carbamazepin and phenytoin were in the low therapeutic ranges, and gabapentin levels were under therapeutic level, our patient had and excellent response. Rectal administration of carbamazepina and gabapentine seems to be an excellent via to administer anticonvulsants in patients who are unable to take oral medications. Rectal administration of baclofen has no place in trigeminal pain.
DOUBLE-BLIND COMPARATIVE TRIAL OF OXCARBAZEPINE VERSUS CARBAMAZEPINE IN NEW-ONSET
A. Beydoun, Neurophysiology & Epilepsy Program, University of Michigan, Ann Arbor, MI , 2 Medical Affairs, Novartis Pharmaceuticals, East Hanover, NJ
Aim of Investigation: Oxcarbazepine (OXC), a keto-analog of carbamazepine (CBZ), has demonstrated comparable efficacy with better tolerability than CBZ, the current treatment of choice for trigeminal neuralgia (TGN). We conducted a clinical trial designed to evaluate the efficacy and tolerability of OXC versus CBZ for symptomatic treatment of new-onset TGN.
Methods: Eligible patients 40 years with new-onset, previously untreated idiopathic TGN were randomized to CBZ or OXC treatment. A 2-4-week titration period (initial dose 300 mg BID OXC or 200 mg BID CBZ titrated to most effective dose) was followed by a 4-week maintenance period. Efficacy variables included: number of attacks, pain-free states, evoked pain, global assessment of efficacy and tolerability.
Results: Forty-six patients were randomized (OXC n=24; CBZ n=22). The most frequently used maintenance doses were: OXC 750 mg/day; CBZ 500 mg/day. There were no significant differences between groups for any efficacy variable. In both groups, 100% were responders and 50% became pain-free. OXC significantly reduced evoked pain in 70% of patients compared to 59% of those treated with CBZ. Global assessments of efficacy and tolerability was rated as good or excellent by 96% and 68% of the OXC patients, respectively, and by 91% and 52% of the CBZ patients, respectively. One patient in the OXC group discontinued due to a rash.
Conclusions: The efficacy and tolerability of OXC are comparable to that of CBZ for patients with new-onset TGN with substantial improvement in spontaneous and evoked pain. OXC appears to be an effective alternative for patients with new-onset TGN.
Acknowledgments: Supported by Novartis Pharmaceuticals.
GABAPENTIN IN PROPHYLACTIC TREATMENT OF MIGRAINE
D. Dolezil I. Mrazkova, M., Neurology, University Hospital, Ostrava, Czech Republic
AIM OF INVESTIGATION:Verification of the effect of gabapentin prophylactic treatment in patients suffering from migraine without and with aura.
METHODS:Overall 49 patients were included to the study during a period from September 1998 till April 2001.42 patients had migraine without aura (M),and 7 patients suffered from migraine with aura (MA) based on IHS criteria.We assesed number of migraine attacks per month,number of days with migraine per month and migraine severity ot scale 0 to 3 (O no pain, 3 severe pain).All patients recorded information on their migraine to their patient diaries.
RESULT:The group of patients with M included 5 men and 37 women and the average duration of the disease in this group was 13 years .The group of patiens with MA included 1 man and 6 woman and the average duration of the disease in this group was 9 years.Gabapentin was administered at a dose 600-1800 mg/day, with the average dose 1080 mg/patient/day, for 6-12 months,with the average duration of treatment of 9,4 months per patient.In the group of patients with M,39 patients (92,8%)responded to the treatment,number of migraine attack/patient/month improved from 4.6 to 1.9,and number of days with migraine per month improved from 6.9 to 2.8.Migraine intensity improved from 2.7 to 1.9.In the group of patients with MA 6 patients(85,7%) responded to the treatment,number attacks/patient/month improved from 4.8 to 1.75, and number of days with migraine per month improved from 7.1 to 2.3, and migraine intesity improved from 2.4 to 1.6.
CONCLUSION:Gabapentin shoved itself as an effective drug in prophylaxis of migraine both without aura (in 92.8% of patients) and with aura (in 85.7 % of patients).Adverse effect were reported in 11 patiens (22.4%), however,treatment had to be interrupted by 1 patient (2%)only. :
USE OF ZONISAMIDE IN PATIENTS WITH NEUROPATHIC PAIN
J. Kunz, University of Wisconsin Pain Treatment and Research Center, Madison, WI
Aim of Investigation: Zonisamide (ZNS) is a novel anticonvulsant with multiple mechanisms of action. This retrospective chart analysis assessed the effectiveness of ZNS in neuropathic pain patients.
Methods: Patients with various types of neuropathic pain were treated with ZNS. Patients rated their pain on a 0-10 scale (0=no pain, 10=worst pain imaginable) prior to ZNS and after reaching maintenance dosage of ZNS.
Results: 11 patients (8 females, 3 males) with various types of neuropathic pain were included; ages ranged from 36-79 years (mean= 49.2 years). 9 patients were on at least 1 other medication for neuropathic pain (range=1-4 medications, mean=2.6). ZNS dosages ranged from 100 mg QOD to 400 mg/d. Mean pre-ZNS pain rating ranged from 3.5-7.5 (mean=5.7). 9 patients were evaluable for efficacy. 7 patients had improvement in their pain ratings (mean improvement=2.1 points); 1 patient had no change, and 1 patient's rating worsened by 1 point during ZNS treatment. 5 patients reported adverse events, including dizziness/unsteadiness (at doses >400 mg/d), tiredness, constipation, heat intolerance/sweating, and decreased sense of taste. All patients were able to tolerate these adverse effects for the benefit of pain relief.
Conclusions: These results indicate ZNS may be effective for treating neuropathic pain in patients who did not achieve satisfactory pain control with other medications. According to this clinical experience, most patients had improvements in neuropathic pain control while taking ZNS. Double-blind, placebo-controlled studies to investigate ZNS in treating neuropathic pain are warranted.
Acknowledgement: Supported by Elan Biopharmaceuticals
ZONISAMIDE IN THE TREATMENT OF NEUROPATHIC PAIN: A RETROSPECTIVE CASE SERIES
M. Royal, Elan Biopharmaceuticals, San Diego, CA , Internal Medicine and Anesthesiology/Pain, Oklahoma University College of Medicine, Tulsa, OK
Aim of Investigation: Zonisamide (ZNS) is a novel anticonvulsant with multiple mechanisms of action, including blockage of sodium and T-type calcium channels, facilitation of dopaminergic and serotonergic neurotransmission, and scavenging of free radicals. This retrospective chart review evaluated ZNS use in patients with various types of neuropathic pain.
Methods: 11 adult neuropathic pain patients who were nonresponders to gabapentin received ZNS as add-on therapy, initiated at 100 mg either every third or every other day. ZNS dosage was increased every 2 weeks, and dosing frequency was increased to every other day and then every day. ZNS dosage titration continued until the maximum effective or maximum tolerated dosage was reached. The McGill Short Form Pain Questionnaire, visual analog scale pain score, patient/physician subjective global response, headache frequency, and headache severity were used to assess response to ZNS. Responses were rated as excellent (>70% improvement in symptoms), good (51-70% improvement), fair (20-50% improvement), or poor (<20% improvement).
Results: Patient global satisfaction responses were excellent in 5 patients, good in 2 patients, and fair in 4 patients. Two patients experienced nausea with ZNS but were able to tolerate ZNS with slower dosage titrations or additional nausea medication. One patient reported irritability and near psychosis, but after dosage adjustments, has been able to tolerate ZNS without problems.
Conclusions: This study suggests ZNS may be a useful addition to the current neuropathic pain armamentarium. Double-blind, placebo controlled trials are warranted to further investigate the use of ZNS in treating neuropathic pain.
Acknowledgement: Supported by Elan Biopharmaceuticals
10th World Congress on Pain. International Association for the Study of Pain, San Diego, California, USA August 17-22, 2002