Neurontin 2000 Research on "off-label" purposes

Percept Mot Skills 2000 Feb;90(1):37-40

Subjective improvement following treatment with carbamazepine (Tegretol) for a subpopulation of patients with traumatic brain injuries.

Persinger MA Department of Psychology, Laurentian University, Sudbury, Ontario, Canada.

Over a 3-yr period, 19 patients who had sustained brain traumas during motor vehicle incidents and who exhibited abnormal scores for a dichotic word-listening task and Roberts' Epileptic Spectrum Disorder Inventory more than one year after the injury were recommended for treatment with carbamazepine (Tegretol). The psychiatric profile of these patients, as defined by the Minnesota Multiphasic Personality Inventory, was similar to the profile of patients from other studies who had displayed more objective improvement following this treatment. Of the 14 patients 12 who followed the recommendation retrospectively reported that within a few weeks after treatment they experienced marked reductions in the incidence of sudden confusion and depression, increased attention and focus, and either elimination or attenuation of an aversive sensed presence. Such results suggest that many of the debilitating symptoms that persist for months to years after a traumatic brain injury may be electrical in nature rather than due to "psychological responses" and might be treatable by appropriate dosages of carbamazepine or other, e.g., Gabapentin (Neurontin) antiepileptic compounds.

Arch Neurol 2000 Apr;57(4):570-1

Dystonia in a patient treated with propranolol and gabapentin.

Palomeras E, Sanz P, Cano A, Fossas P Unit of Neurology, Hospital de Mataro, Spain. neurologia2@csm.scs.es

We present a 68-year-old patient with essential tremor who was treated with propranolol hydrochloride (80 mg daily) and gabapentin (900 mg daily) after a history of mild success of gabapentin alone in relieving his symptoms. The patient had several daily episodes of paroxysmal dystonic movements in both hands. After reducing the propranolol dose to 40 mg daily, the dystonic movements resolved. This case suggests a synergistic effect between propranolol and gabapentin.

Neurol Neurochir Pol 2000;33 Suppl 1:13-20

[GABA-ergic system and antiepileptic drugs].[Article in Polish]

Czuczwar SJ Katedra i Zaklad Farmakologii i Toksykologii, Akademii Medycznej w Lublinie. czuczwar@galen.imw.lublin.pl

gamma-Aminobutyric acid (GABA) belongs to main inhibitory neurotransmitters in the central nervous system and activates three types of specific receptors--GABAA, GABAB i GABAC. At present, little is known about GABAC-mediated events. GABAB receptors are metabotropic, whilst stimulation of ionotropic GABAA receptors results in opening the chloride channel, followed by influx of chloride ions and hyperpolarization. The GABAA receptor possesses also binding sites for benzodiazepines and barbiturates which, via these sites, enhance GABAA-mediated events. Another antiepileptic drug potentiating GABA-ergic inhibition is valproate, which increases synthesis of GABA and reduces its metabolism. Among new antiepileptic drugs associated with the GABA-ergic system are tiagabine, vigabatrin, and to a certain degree--gabapentin. Tiagabine blocks neuronal and glial uptake of GABA whilst vigabatrin increases the synaptic concentration of GABA by inhibition of GABA aminotransferase. Gabapentin, probably through the activation of glutamic acid decarboxylase, leads to the increase in synaptic GABA. However, this antiepileptic drugs is also binds to specific sites within voltage-dependent calcium channels, which results in the reduced intraneuronal concentration of calcium ions. Presumably, tiagabine and vigabatrin possess only one mechanism of action, associated with the increased GABA-ergic inhibition. Although topiramate and felbamate were shown to enhance GABA-mediated events, they have additional mechanisms of action, including blockade of voltage-dependent sodium channels and inhibition of glutamatergic neurotransmission.

Epilepsia 2000 Apr;41(4):479-81

Myoclonus associated with the use of gabapentin.

Asconape J, Diedrich A, DellaBadia J Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5250, USA. jasconap@iuoui.edu

PURPOSE: To report on the occurrence of myoclonus in patients receiving gabapentin (GBP) for the treatment of epilepsy. METHODS: Clinic charts of 104 consecutive patients started on GBP were reviewed. All patients were treated by the same physician, and most were specifically asked about the presence of myoclonus. RESULTS: We found 13 cases of myoclonus. All patients had refractory epilepsy and were taking other antiepileptic drugs (AEDs). Six patients had a severe chronic static encephalopathy; five patients had no medical diagnosis other than seizures. Ten patients developed multifocal myoclonus. Three patients developed focal myoclonus, contralateral to their epileptic focus. Two patients had an exacerbation of preexistent myoclonus. An EEG performed during myoclonus on three patients showed no correlate. The myoclonus tended to persist as long as GBP was maintained, whereas discontinuance of GBP resulted in rapid cessation of the myoclonus. In all cases the myoclonus was subtle and did not significantly interfere with daily activities. CONCLUSIONS: GBP-associated myoclonus appears to be relatively frequent. It is usually mild and can easily be overlooked. Discontinuation of therapy is not necessary in most cases.

Pediatr Neurol 2000 Mar;22(3):220-1

Use of gabapentin in the treatment of childhood reflex sympathetic dystrophy.

Wheeler DS, Vaux KK, Tam DA Department of Pediatrics and Clinical Investigations, Naval Medical Center, San Diego, California, USA.

Reflex sympathetic dystrophy, a painful syndrome involving an extremity after trauma or injury, is increasingly reported in the pediatric population. Although no clear pathophysiologic mechanism for this disorder has been identified, the role of central serotonin activity seems important. Gabapentin, a new antiepileptic medication, has been demonstrated to be effective in adults with reflex sympathetic dystrophy. The first reported case of a child with a diagnosis of reflex sympathetic dystrophy who was treated successfully with gabapentin is presented.

J Clin Psychiatry 2000 Feb;61(2):79-90

Mood stabilizers during breastfeeding: a review.

Chaudron LH, Jefferson JW William S. Middleton Memorial Veterans Affairs Hospital and the University of Wisconsin Medical School, USA.

BACKGROUND: The postpartum period is an exceptionally high-risk time for recurrence of depression, mania, or psychosis for women with bipolar disorder. Puerperal prophylaxis with mood stabilizers decreases this risk. To allow patients and clinicians to make informed decisions about mood-stabilizer use during breastfeeding, there is a need for a critical review and analysis of the data. DATA SOURCES: A search of MEDLINE (1966-1998) and the Lithium Database, Madison Institute of Medicine, was conducted to obtain articles about lithium, valproate, carbamazepine, gabapentin, or lamotrigine use during lactation. Search terms used were pregnancy, teratogenesis, breastfeeding, lactation, breast milk levels and lithium, anticonvulsants, mood stabilizers. No other search restrictions were used. Unpublished data on gabapentin and lamotrigine were provided by the manufacturers. RESULTS: The search revealed 11 cases of lithium use during breastfeeding, 8 of which reported infant serum levels. Two cases reported symptoms consistent with lithium toxicity in the infants. Thirty-nine cases of valproate use during breastfeeding were found, 8 of which reported infant serum levels. There was 1 report of thrombocytopenia and anemia in an infant. Fifty cases of carbamazepine use during breastfeeding were found, 10 of which reported infant serum levels. Two infants experienced hepatic dysfunction. One unpublished study of gabapentin in breast milk was found. Three reports of lamotrigine use during breastfeeding were found. DISCUSSION: Available information remains limited to uncontrolled studies and case reports. Carbamazepine and valproate, but not lithium, have generally been considered compatible with breastfeeding. The overall paucity of data, data confounded by polypharmacy and infant age differences, and adverse reactions reported with all established mood stabilizers dictate a reassessment of these recommendations. We propose that a woman's historical response to medication and the clinical circumstances be the primary considerations when choosing a mood stabilizer during breastfeeding, rather than strict adherence to categorical assignments.

South Med J 2000 Mar;93(3):335-6

Improved sexual function in three men taking lamotrigine for epilepsy.

Husain AM, Carwile ST, Miller PP, Radtke RA Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.

Little information exists about the effects of newer antiepileptic drugs (AEDs) on sexual function in men with epilepsy. We report a series of three male veterans whose sexual disorders improved with lamotrigine. All three had partial seizures. One patient was taking phenobarbital and gabapentin and complained of decreased potency and anorgasmia. After lamotrigine was added for better seizure control and the dosage of gabapentin was tapered, anorgasmia improved. The second patient complained of impotence after a rash while taking phenytoin and carbamazepine. Impotence persisted with phenobarbital, valproate, and gabapentin. Eight months after gabapentin was replaced with lamotrigine, impotence improved. The third patient complained of long-standing impotence. Treatment with five AEDs had no effect on the dysfunction. Lamotrigine was added to the carbamazepine regimen; impotence improved with decrease in carbamazepine and increase in lamotrigine. The favorable effect of lamotrigine on sexual disorders in these three patients suggests this drug should be considered under appropriate circumstances for men who have sexual dysfunction while taking other antiepileptic agents.

Neurology 2000;54(5 Suppl 1):S25-32

Effect of anticonvulsants on nocturnal sleep in epilepsy.

Placidi F, Diomedi M, Scalise A, Marciani MG, Romigi A, Gigli GL Clinica Neurologica Universita Tor Vergata, IRCCS Clinica S. Lucia Roma, Rome, Italy.

Our objective was to determine, in three separate studies, the effects of controlled-release carbamazepine (CBZ-CR), lamotrigine (LTG), and gabapentin (GBP) on nocturnal sleep in epilepsy. Antiepileptic drugs (AEDs) control seizures and also modify hypnic structure. Despite widespread clinical use, their effects on sleep are not well known. PSG was performed in all three studies as follows: CBZ-CR: at baseline, after initial administration of CBZ-CR 400 mg, and after 1 month of CBZ-CR treatment (400 mg BID) in a sample of seven temporal lobe epileptic (TLE) patients. Results were compared with those of nine healthy volunteers; LTG: at baseline, after 3 months of stable treatment with LTG (300 mg/day); GBP: at baseline, after 3 months of stable treatment with GBP (1800 mg/day). Significant findings are as follows for each study. The acute administration of CBZ-CR increased number of stage shifts, reduced REM sleep, and increased REM sleep fragmentation. In the TLE group, these effects were almost completely reversed after chronic treatment. LTG increased REM sleep, reduced number of entries into REM sleep, decreased number of phase shifts, and decreased percentage of slow-wave sleep. GBP increased REM sleep percentage, increased mean duration of REM periods, reduced number of awakenings, and reduced stage 1 sleep percentage. We conclude that CBZ-CR disrupts REM sleep, but only during acute administration. LTG and GBP improve sleep stability while reducing seizures.

South Med J 2000 Feb;93(2):238-42

Interstitial cystitis and the potential role of gabapentin.

Hansen HC Pain Relief Centers, PA, Hickory, NC, USA.

Gabapentin, an antiepileptic agent, is a safe and versatile medication also used in the adjunctive treatment of painful disorders. These include neuropathic pain, such as postherpetic neuralgia, diabetic neuropathy, and the pain of reflex sympathetic dystrophy. Interstitial cystitis, a painful disease entity, shares many common features of these chronic pain states, and the use of gabapentin can assist in pain control. Gabapentin, as an adjunctive agent, may reduce use of cotherapeutics such as narcotics. Two patients with interstitial cystitis improved functional capacity within their activities of daily living and received adequate pain control with the addition of gabapentin to their medication regimen.

J Neuropsychiatry Clin Neurosci 2000 Winter;12(1):40-3

Treatment of dementia-associated agitation with gabapentin.

Roane DM, Feinberg TE, Meckler L, Miner CR, Scicutella A, Rosenthal RN Department of Psychiatry and the Neurobehavior and Alzheimer's Disease Center, Beth Israel Medical Center, New York, NY 10003, USA.

The authors describe the use of gabapentin in the treatment of 4 outpatients with dementia-associated agitation. On the basis of clinical case reports and the Overt Agitation Severity Scale, all 4 patients had reduced agitation with gabapentin. Three of 4 patients were successfully titrated to a full dose of 2,400mg/day. These findings suggest a possible role for gabapentin in the behavioral management of patients with dementia.

Clin Neuropharmacol 2000 Jan-Feb;23(1):53

Asterixis induced by gabapentin.

Jacob PC, Chand RP, Omeima el-S Department of Medicine (Neurology), College of Medicine, Sultan Qaboos University, Muscat, Oman.

We report the case of a patient with postherpetic neuralgia who developed asterixis while being treated with gabapentin. We discuss the possible mechanism of asterixis in this patient.

N.B. Asterixis is a motor disturbance characterized by intermittent lapses of postural tone, producing flapping movements particularly of the outstretched arms; seen with such conditions as hepatic coma, uremia, and respiratory acidosis.] Clin Neuropharmacol 2000 Jan-Feb;23(1):45-9

Gabapentin treatment for muscle cramps: an open-label trial.

Serrao M, Rossi P, Cardinali P, Valente G, Parisi L, Pierelli F Institute for Nervous and Mental Diseases, Universita degli studi di Roma La Sapienza, Italy.

To evaluate the efficacy and safety of gabapentin in the treatment of muscle cramps, we engaged an open-label trial with a group of 30 patients with frequent (> 5 cramps/week), stable, long-lasting cramps, associated with different diseases. Gabapentin was effective in reducing the frequency and severity of muscle cramps and associated sleep disturbances (clinical outcome measures) within the first 2 weeks of medication at 600 mg/d. At the 1 month control (mean dosage, 825 +/- 35 mg), almost every patient had responded to treatment and two thirds experienced a total remission of symptoms. After 3 months of therapy (mean dosage, 892 +/- 180 mg), cramps disappeared in 100% of patients and this benefit persisted as long as 6 months. Additionally, we evaluated in 10 patients the Cramps Threshold Frequency (CTF) (neurophysiological outcome measure) before and during gabapentin treatment. Gabapentin significantly increased the CTF, returning it to normal values. With the limitation of an open-label methodology, our clinical and neurophysiologic experience suggests that a gabapentin dose of 600-1200 mg/d would be helpful in the treatment of muscular cramps.

Pediatr Neurol 2000 Jan;22(1):68-71

Gabapentin treatment in a child with delayed-onset hemichorea/hemiballismus.

Kothare SV, Pollack P, Kulberg AG, Ravin PD Division of Pediatric Neurology, University of Massachusetts Memorial Health Care, Worcester 01655-0318, USA.

A 13-year, 6-month-old female was evaluated for subacute onset of left-sided hemichorea/hemiballismus, with an old, right parietal, cortical, and subcortical stroke as the presumed cause. Treatment with gabapentin was initiated, with good results at 6-month follow-up. Discussion of the differential diagnosis and evaluation of delayed-onset movement disorders in children and the mechanism of action of gabapentin is included.

Arch Phys Med Rehabil 2000 Feb;81(2):164-9

Gabapentin effect on spasticity in multiple sclerosis: a placebo-controlled, randomized trial.

Cutter NC, Scott DD, Johnson JC, Whiteneck G University of Colorado Health Sciences Center, Denver, USA.

OBJECTIVE: To investigate the effect of gabapentin on subject self-report and physician-administered spasticity scales in individuals with multiple sclerosis. DESIGN: Prospective, double-masked, placebo-controlled, crossover design. SETTING: The Multiple Sclerosis Center at the Denver Veterans Affairs Medical Center. INTERVENTION: Subjects were titrated to either 900 mg gabapentin orally three times a day or placebo over a 6-day period. Subjects underwent a 14-day washout and then were crossed over. No other changes were made to their medication regimen. MAIN OUTCOME MEASURES: The outcome measures were divided into two categories: subject self-report scales physician-administered scales. Subject self-report scales included the spasm frequency scale, spasm severity scale, interference with function scale, painful spasm scale, and global assessment scale. Physician-administered scales included the Modified Ashworth Scale, clonus scale, deep tendon reflexes, plantar stimulation response, and the Kurtzke Expanded Disability Status (EDSS) Scale. Digit Span and Digit Symbol subtests of the WAIS-R Intelligence Scale were administered to assess for possible impaired concentration. The Fatigue Impact Scale was administered to assess for changes in fatigue. The adjective generation technique was administered to assess for alterations in mood. RESULTS: A statistically significant reduction in the impairment of spasticity was found in the gabapentin-treated subjects compared with placebo as measured by the self-report scales of the spasm severity scale, interference with function scale, painful spasm scale, and global assessment scale and by the physician-administered scales of the Modified Ashworth and plantar stimulation response. No significant difference was noted in the Digit Span, Digit Symbol, adjective generation technique, and EDSS. CONCLUSION: Gabapentin reduces the impairment of spasticity, compared with placebo, without the side effects of worsening concentration and fatigue.

Seizure 2000 Jan;9(1):47-50

Conversion from thrice daily to twice daily administration of gabapentin (GBP) in partial epilepsy: analysis of clinical efficacy and plasma levels.

Muscas GC, Chiroli S, Luceri F, Mastio MD, Balestrieri F, Arnetoli G Epilepsy Center, Department of Neurology, Careggi Hospital, Florence, Italy.

Gabapentin has been administered in placebo-controlled studies with a thrice daily (T.I.D.) schedule, because of its short half-life. However, clinical efficacy does not seem strictly related to plasma levels: a twice daily (B.I.D.) schedule might therefore be possible. The aim of our study was to verify if the conversion from a T.I.D. to a B.I.D. regimen affected the efficacy and safety of gabapentin therapy. Out of 171 patients treated with add-on gabapentin, we selected 29 stable responders, who were followed for three months with a T.I.D. schedule and then switched to B.I.D. regimen for further three months. Seizure number, side-effects and trough plasma levels of gabapentin were collected during both periods. Gabapentin mean dose was 2117.2 mg/day. Mean number of seizures/months was: 4.2 at baseline, 1.0 during the T.I.D., and 0.9 during the B.I.D. period. Mean trough plasma level of gabapentin was 5.9 microgram/ml during the T.I.D. and 5.2 microgram/ml during the B.I.D. period. Twelve side-effects were reported by 11 patients during the T.I.D. and 6 by 5 patients during the B.I.D. period., sedation and vertigo were the most frequent in both. Results of our study suggest that gabapentin can be administered safely and effectively either with a T.I.D. and a B.I.D. regimen.

J Clin Psychopharmacol 2000 Feb;20(1):90-3

Effectiveness of gabapentin for the treatment of behavioral disorders in dementia.

Herrmann N, Lanctot K, Myszak M Division of Geriatric Psychiatry, University of Toronto, Ontario, Canada. nathan.herrmann@sunnybrook.on.ca

Twelve patients with moderate to severe dementia and severe behavioral disorders were treated with open-label gabapentin (200-1,200 mg/day) for 8 weeks in a prospective case-series design. Patients were nonresponders to previous trials of neuroleptics. Behaviors were measured at 2-week intervals with the Neuropsychiatric Inventory (NPI), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression Scale (CGI). Gabapentin was generally well tolerated in this population. Although 42% of patients experienced adverse events such as gait instability and sedation, only two patients discontinued treatment prematurely because of adverse events. Average patient scores for the CMAI and the NPI remained unchanged after gabapentin. On the CGI, two patients were much improved, three were minimally improved, six were unchanged, and one was minimally worse. Gabapentin may have a role in treating a subgroup of dementia patients with severe behavioral disorders who have not responded to neuroleptics.

Rev Neurol 1999 Dec 16-31;29(12):1147-53

[The effect of gabapentin in bucco-facial allodynia. Experimental correlation of the trigeminal nerve].

[Article in Spanish] Guerrero-Figueroa R, Escobar-Juyo A, Caballero-Garcia G, Blanco-Castillo IP Tulane University-School of Medicine, New Orleans, USA.

INTRODUCTION: Trigeminal neuralgia is an unilateral alteration of the trigeminal nerve, characterized by recurrent paroxysms of pain in one or more of the nerve's branches. Trigger areas are described in points of the facial skin (allodynia). OBJECTIVE: To evaluate the effects of gabapentin (monotherapy) and associated with carbamazepine in allodynia of trigeminal neuralgia. PATIENTS AND METHODS: The effects of these drugs were studied in 14 patients with trigeminal allodynia and with 12 experimental cats, with microelectrodes of multiple connections in the central nervous system and in dental pulp to precipitate pain in injured zones, area of primary hyperalgesia, secondary hyperalgesia and allodynia zone. Unitary registrations and evoked potentials were evaluated in neuronal trigeminal organizations, encephalon, limic system and neocortex. RESULTS: The pairing of innocuous stimulus (allodynia) plus painful stimulus precipitate classic conditioned reflex. Unitary alteration and evoked potentials correlated with learning and memory were evaluated, involving the hippocampus in the results. The allodynia treatment obtains better results with the combined treatment than with the monotherapy. CONCLUSIONS: Allodynia can be the result of a neuronal sensitization due to the increment on intracellular calcium facilitating the exocytosis. Changes in the mechano-receptors of low threshold establish communication with nociceptive neurons by a presynaptic mechanism, considering new synaptic and morphologic contacts associated with learning and memory. The major effectiveness in the combined treatment is the base of an association of the gabaergic mechanism of gabapentin and the blockade of sodium and potassium ionic channels by the carbamazepine.

Neurology 2000 Jan 11;54(1):58-64

Pharmacologic reversal of cortical hyperexcitability in patients with ALS.

Caramia MD, Palmieri MG, Desiato MT, Iani C, Scalise A, Telera S, Bernardi G Clinica Neurologica, Department of Neuroscience, Universita di Roma Tor Vergata, and the IRCCS, S. Lucia, Rome, Italy. mwjones@ats.it

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with ALS by administering drugs that promote GABAergic transmission. BACKGROUND: Transcranial magnetic stimulation (TMS) has revealed abnormalities of cortical inhibition in ALS, a reduction of the silent period, and the absence of intracortical inhibition normally occurring in response to paired TMS. Impaired inhibitory transmission could play a role in the physiopathology of this illness. METHODS: Using paired TMS with conditioning stimuli from 1-to-6-msec-interstimulus intervals, we investigated 16 patients with ALS. The protocol included: (1) the "drug-free" profile of paired TMS; (2) paired TMS 30 minutes after the intake of diazepam (3.5 mg); (3) paired TMS after 3 weeks' treatment with gabapentin (GBP) (600 mg/day) or riluzole (50 mg/twice a day). RESULTS: Intracortical inhibition is lost in patients with ALS, and this abnormal profile is reversed by diazepam or sustained treatment with GBP. We also noted that motor-evoked potential amplitudes to single stimuli increased (p<0.01) after diazepam and GBP. CONCLUSIONS: The demonstration of pharmacologic reversal of hyperexcitability in patients with ALS makes a potentially significant contribution toward understanding the pathophysiology of a disease that has so far eluded an effective cure.

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