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PubMed2000

Antinociceptive effect of systemic gabapentin in mononeuropathic rats, depends on stimulus characteristics and level of test integration.

The anticonvulsant gabapentin is effective against neuropathic pain, but the primary site(s) and mechanism(s) of action are unknown. In order to explore the relative contribution of spinal versus supra-spinal mechanisms to the antinociceptive effect of gabapentin, this study used two differentially integrated nociceptive tests. We systematically compared the effects of various doses of gabapentin on the paw withdrawal to pressure (PWTP), a spinally coordinated reflex and the vocalization threshold to paw pressure (VTPP), a supra-spinal integrated test in the sciatic nerve constriction rat model of neuropathic pain. In addition, we evaluated the effect of gabapentin on the struggle latency to paw immersion into a non-noxious cold (10 degrees C) water bath. Similar lower doses (1-30 mg/kg) of gabapentin produced potent antinociception in the VTPP test but were devoid of effects on the PWTP. The effect was observed not only on the nerve-injured side, but also, although less pronounced, on the contralateral side. Only the highest dose (100 mg/kg) of the anticonvulsant was able to induce an increase in the nerve-injured paw threshold in both tests. In the thermal test, gabapentin (3, 10 and 30 mg/kg i.p.) dose-dependently increased the response time to the 10 degrees C stimulus. Gabapentin at 100 mg/kg but not at 30 mg/kg produced motor deficits in animals using the rotarod test. Taken together, our findings suggest that low doses of gabapentin have a preferential action on the more integrated pain-related behaviour in neuropathic rats. The present results confirm that gabapentin may be a useful approach for the clinical management of several aspects of neuropathic pain.

Acetates↗
PubMed1997

Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test.

The antinociceptive effects of the combination of spinal morphine and gabapentin were evaluated in the tail-flick test in rats. The intrathecal coadministration of a subantinociceptive dose of morphine at 0.2 microgram and gabapentin at 300 micrograms produced significant antinociception. Pretreatment with spinal gabapentin at 300 micrograms shifted the dose-response curve of spinal morphine to the left with a decrease in morphine ED50 value from 1.06 micrograms to 0.34 microgram. The antinociceptive effects produced by the combination of a subantinociceptive dose of morphine and gabapentin were reversed by spinal naloxone at 30 micrograms but were not reversed by spinal bicuculline at 0.3 microgram. Furthermore, the concurrent administration of spinal naloxone at 30 micrograms with the combination of morphine and gabapentin blocked antinociception, while the concurrent administration of spinal bicuculline at 0.3 microgram failed to prevent antinociception. These results indicate that the combination of spinal gabapentin and morphine produces an enhancement of antinociception that appears to involve the spinal mu opioid receptors. Furthermore, repeated administration of gabapentin for 3 days did not affect the enhancing effect of gabapentin on the antinociceptive effect of morphine, indicating that tolerance did not develop to gabapentin's ability to enhance morphine antinociception.

Acetates↗
PubMed2006

Gabapentin attenuates late but not acute pain after abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Gabapentin has been suggested to decrease acute postoperative pain. We evaluated the effect of gabapentin on pain after abdominal hysterectomy. METHODS: Sixty patients scheduled for abdominal hysterectomy were randomized to receive orally gabapentin 400 mg 6 hourly or placebo. Treatment started 18 h preoperatively and continued for 5 postoperative days. Pain (visual analogue score) and consumption of morphine for 48 h and of oral paracetamol/codeine were recorded after 2, 4, 8, 24 and 48 h and on days 3-5 postoperatively. After 1 month, patients were interviewed by phone for pain, and analgesic intake after hospital discharge. RESULTS: Morphine consumption (mean +/- SD) was 35 +/- 15.7 mg in the control and 28 +/- 12.1 mg in the gabapentin group (P = 0.21). Median number (range) of paracetamol 500 mg/codeine 30 mg tablets taken during days 3-5 was 1.0 (0-6) in the control and 2.0 (0-9) in the gabapentin group (P = 0.35). The visual analogue scores at rest and after cough did not differ between the two groups (F = 0.92, df = 1, P = 0.34 and F = 0.56, df = 1, P = 0.46, respectively). One month after surgery, 22/27 (81%) of the control group and 9/25 (36%) of the gabapentin group reported pain in the surgical area (chi(2) = 11.15, P = 0.002), while 11/27 (41%) of controls and 7/25 (28%) of gabapentin patients consumed analgesics for pain (chi(2) = 0.93, P = 0.39). The intensity of pain was decreased in the gabapentin group (chi(2) = 12.6, P = 0.003). CONCLUSIONS: Gabapentin has no effect on immediate pain after abdominal hysterectomy but decreases pain 1 month postoperatively.

Acetaminophen↗
PubMed2000

Gabapentin use in neuropathic pain syndromes.

The development of neuropathic pain involves a series of changes including primary and secondary hyperalgesia, peripheral and central sensitization, and wind-up phenomena. Neurotransmitters play a critical role in this process. For example, glutaminergic subtypes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and neurokinin prime the N-methyl-D-aspartate (NMDA) receptor by triggering the release of intracellular calcium ions, thus unblocking the magnesium ion plug on the NMDA receptor and allowing Ca2+ influx into the cell. Ca2+ ions acting as secondary messengers initiate protein kinase C activation, phospholipase C and nitric oxide synthetase production, and proto-oncogene expression. The activation of the NMDA receptor thereby increases the responsiveness of the nociceptive system. Anticonvulsant drugs--including carbamazepine, phenytoin, and felbamate--have been used to treat neuropathic pain. Gabapentin is a novel anticonvulsant that may have a unique effect on voltage-dependent Ca2+ channel currents at postsynaptic dorsal horn neurons. Thus, gabapentin may interrupt an entire series of events, not just a single process, that lead to the development of neuropathic pain. Preclinical models of anti-inflammatory and neuropathic pain indicate that gabapentin effectively antagonizes the maintenance of this pain. Additionally, in preemptive surgical models, gabapentin has been shown to prevent the induction of pain. Gabapentin has been shown to be efficacious in numerous smaller clinical studies, case reports, and chart reviews in a variety of neuropathic pain syndromes. Two large multicenter studies, one in postherpetic neuralgia (PHN) and one in diabetic peripheral neuropathy (DPN), support preclinical findings. In the PHN study, patients treated with gabapentin demonstrated a significant difference (P<0.001) in their average daily pain score at endpoint compared to placebo patients. In the DPN trial, mean weekly pain was significantly (P<0.001) different for gabapentin-treated patients compared to placebo-treated patients at endpoint. Consistent with the known side-effect profile of gabapentin, the most common adverse events noted in both studies were dizziness and somnolence. Gabapentin should be considered an important addition to the management of neuropathic pain syndromes.

Acetates↗
PubMed2002

Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones.

1. This study examined the action of gabapentin (gabapentin,1-(aminomethyl) cyclohexane acetic acid (Neurontin) on voltage-gated calcium (Ca(2+)) channel influx recorded in cultured rat dorsal root ganglion (DRG) neurones. 2. Voltage-gated Ca(2+) influx was monitored using both fura-2 based fluorescence Ca(2+) imaging and the whole-cell patch clamp technique. 3. Imaging of intracellular Ca(2+) transients revealed that gabapentin inhibited KCl (30 mM)-evoked voltage-dependent Ca(2+) influx. Both the duration for 50% of the maximum response (W50) and total Ca(2+) influx were significantly reduced by approximately 25-30% in the presence of gabapentin (25 microM). 4. Gabapentin potently inhibited the peak whole-cell Ca(2+) channel current (I(Ba)) in a dose-dependent manner with an estimated IC(50) value of 167 nM. Block was incomplete and saturated at a maximal concentration of 25 microM. 5. Inhibition was significantly decreased in the presence of the neutral amino acid L-isoleucine (25 microM) but unaffected by application of the GABA(B) antagonist, saclofen (200 microM), suggesting a direct action on the alpha(2)delta subunit of the Ca(2+) channel. 6. Gabapentin inhibition was voltage-dependent, producing an approximately 7 mV hyperpolarizing shift in current voltage properties and reducing a non-inactivating component of whole-cell current activated at relatively depolarized potentials. 7. The use of specific Ca(2+) channel antagonists revealed a mixed pharmacology of the gabapentin-sensitive current (N-, L- and P/Q-type), which is dominated by N-type current. 8. The present study is the first to demonstrate that gabapentin directly mediates inhibition of voltage-gated Ca(2+) influx in DRG neurones, providing a potential means for gabapentin to effectively mediate spinal anti-nociception.

Acetates↗
PubMed2002

Gabapentin in the treatment of neuropathic pain after spinal cord injury: a prospective, randomized, double-blind, crossover trial.

BACKGROUND: Neuropathic pain is a common complaint after traumatic spinal cord injury (SCI). Gabapentin, a synthetic structural analogue of GABA, has been shown to have beneficial effects in the treatment of neuropathic pain in other diagnostic groups; however, no standardized clinical trial has been performed to evaluate its efficacy after SCI. DESIGN: A 10-week, prospective, randomized, double-blind, crossover, and placebo-controlled clinical trial. OBJECTIVE: To determine the efficacy of gabapentin in the treatment of SCI-related neuropathic pain. METHODS: Seven subjects with neuropathic pain, who were more than 30 days post-SCI, completed the study. Two groups received a 4-week course of gabapentin and placebo in a randomized crossover design with a 2-week washout period. The Neuropathic Pain Scale was used to record daily pain levels. Data were analyzed using the Wilcoxon signed rank test. RESULTS: Gabapentin has some beneficial effects on certain types of neuropathic pain. There was a significant decrease of "unpleasant feeling" and a trend toward a decrease in both the "pain intensity" and "burning sensation" at the fourth week of gabapentin treatment compared with those on the placebo. No significant difference was found among other pain descriptors during the gabapentin and placebo treatment, although this may have been limited by the small sample size and low maximum dosage of gabapentin. CONCLUSIONS: Gabapentin reduces certain types of neuropathic pain in the SCI population. Future studies with larger sample sizes, higher dosages, and quicker titration will help further determine the efficacy of gabapentin in the treatment of SCI-related neuropathic pain.

Acetates↗
PubMed2002

Gabapentin for the treatment of pain in guillain-barré syndrome: a double-blinded, placebo-controlled, crossover study.

UNLABELLED: Pain syndromes of Guillain-Barré are neuropathic as well as nociceptive in origin. We aimed to evaluate the therapeutic efficacy of gabapentin in relieving the bimodal nature of pain in Guillain-Barré syndrome in a randomized, double-blinded, placebo-controlled, crossover study in 18 patients admitted to the intensive care unit for ventilatory support. Patients were assigned to receive either gabapentin (15 mg. kg(-1). d(-1) in 3 divided doses) or matching placebo as initial medication for 7 days. After a 2-day washout period, those who previously received gabapentin received placebo, and those previously receiving placebo received gabapentin as in the initial phase. Fentanyl 2 micro g/kg was used as a rescue analgesic on patient demand or when the pain score was >5 on a numeric rating scale of 0-10. The numeric rating score, sedation score, consumption of fentanyl, and adverse effects were noted, and these observed variables were compared. The numeric pain score decreased from 7.22 +/- 0.83 to 2.33 +/- 1.67 on the second day after initiation of gabapentin therapy and remained low during the period of gabapentin therapy (2.06 +/- 0.63) (P < 0.001). There was a significant decrease in the need for fentanyl from Day 1 to Day 7 during the gabapentin therapy period (211.11 +/- 21.39 to 65.53 +/- 16.17 [ micro g]) in comparison to the placebo therapy period (319.44 +/- 25.08 to 316.67 +/- 24.25 [ micro g]) (P < 0.001). IMPLICATIONS: Gabapentin, an antiepileptic drug, has been used effectively for different types of pain management. This study demonstrates that gabapentin has minimal side effects and is an alternative to opioids and nonsteroidal antiinflammatory drugs for management of the bimodal nature of pain of Guillain-Barré Syndrome patients.

Acetates↗
PubMed2000

Antiallodynic effect of intrathecal gabapentin and its interaction with clonidine in a rat model of postoperative pain.

BACKGROUND: Systemic administration of gabapentin was shown previously to attenuate mechanical allodynia in a rat model of postoperative pain. Because intrathecal administration of gabapentin is effective in other hypersensitivity states, the authors tested its effect in the postoperative model, its interaction with another antiallodynic agent (clonidine), and a possible mechanism of gabapentin action (entry into sites of action via an L-amino acid transporter). METHODS: Male Sprague-Dawley rats were anesthetized with halothane, and an incision of the plantaris muscle of right hind paw induced punctate mechanical allodynia. Withdrawal threshold to von Frey filament application near the incision site was determined before and 2 h after surgery. Then, an intrathecal injection was performed and thresholds were determined every 30 min for 3 h thereafter. RESULTS: Paw incision induced a mechanical hypersensitivity (mechanical threshold > 25 g before incision and < 5 g after). Intrathecal gabapentin dose-dependently (10-100 microg) reduced mechanical allodynia. Intrathecal injection of an inhibitor of L-amino acid transporters or a competitor for this transporter, L-leucine, did not reverse the intrathecal effect of gabapentin. The ED50 of intrathecal gabapentin, clonidine, and their combination were 51, 31, and 9 microg, respectively, and isobolographic analysis showed synergy between gabapentin and clonidine. CONCLUSIONS: Intrathecal gabapentin is effective against tactile allodynia that occurs after paw incision, and interacts synergistically with clonidine. Unlike results in vitro, gabapentin does not obligatorily need to enter cells via the L-amino acid transporter mechanism to achieve its effects in vivo.

Acetates↗
PubMed2003

Gabapentin markedly reduces acetic acid-induced visceral nociception.

BACKGROUND: Gabapentin has recently been used clinically as an antihyperalgesic agent to treat certain neuropathic pain states. The aim of this study is to test whether gabapentin is able to inhibit responses to peritoneal irritation-induced visceral pain and to examine the effect of gabapentin on spinal cord amino acid release. METHODS: The acetic acid-induced writhing assay was used in rats to determine the degree of antinociception. The rats received an intraperitoneal injection of acetic acid 40 min after intraperitoneal administration of vehicle or gabapentin (50, 100, or 200 mg/kg). Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space in anesthetized rats. Acetic acid-induced release of amino acids into the dialysate, including glutamate, aspartate, serine, glutamine, and glycine, following intraperitoneal injection of acetic acid was evaluated by measurements of changes in the concentrations of these amino acids. The effects of pretreatment with saline or gabapentin (100 mg/kg intraperitoneal) on amino acid release were compared. RESULTS: Gabapentin reduced writhing responses in a dose-related fashion. Dialysate concentrations of glutamate, aspartate, and serine increased significantly following intraperitoneal injection of acetic acid, while glutamine and glycine concentrations were not increased significantly. When compared to saline-treated rats, animals pretreated with 100 mg/kg gabapentin showed suppression of the acetic acid-induced increases in glutamate, aspartate, and serine concentrations. CONCLUSIONS: These data demonstrate that gabapentin effectively inhibits acetic acid-induced nociception, and the antinociceptive effect of gabapentin correlates with the suppression of noxious-evoked release of excitatory amino acids in the spinal cord.

Acetates↗
PubMed2003

Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain.

BACKGROUND: Gabapentin, a gamma-aminobutyric acid analog anticonvulsant, has been shown to possess antinociceptive effects in animal models and clinical trials. An endogenous binding site of [3H]gabapentin has been revealed to be the alpha(2)delta subunit of voltage-dependent Ca2+ channels. Magnesium chloride, ruthenium red, and spermine have been shown to modulate [3H]gabapentin binding to this binding site in vitro. In this study, the authors examined whether intrathecal magnesium chloride, ruthenium red, or spermine could affect the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. METHODS: Under isoflurane anesthesia, male Sprague-Dawley rats received an incision over the plantar surface of the right hind paw to produce punctate mechanical allodynia. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before incision, 2 h after incision, and every 30 min after intrathecal coadministration of gabapentin with normal saline or different doses of magnesium chloride, ruthenium red, or spermine for 2 h. RESULTS: Intrathecal gabapentin (30, 100, 200 microg) dose-dependently reduced incision-induced allodynia. Hexahydrated magnesium chloride (5, 10, 20 microg) and ruthenium red (0.2, 2, 20 ng) noncompetitively inhibited the antiallodynic effect of gabapentin. Spermine at doses not inducing motor weakness (30, 60 microg) did not affect the antiallodynic effect of gabapentin. The antiallodynic effect of intrathecal morphine (1.5 microg) was not affected by hexahydrated magnesium chloride (20 microg), ruthenium red (20 ng), or spermine (60 microg). CONCLUSIONS: These results provide behavioral evidence to support that the alpha(2)delta subunit of Ca2+ channels may be involved in the antiallodynic action of intrathecal gabapentin in the postoperative pain model.

Acetates↗
PubMed2006

Gabapentin, estrogen, and placebo for treating hot flushes: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of gabapentin, estrogen, and placebo in the treatment of hot flushes. METHODS: We performed a randomized, double-blind, placebo-controlled trial of 60 postmenopausal women to assess the efficacy of estrogen and gabapentin in the treatment of moderate-to-severe hot flushes. Participants were randomly assigned to receive either 0.625 mg/d of conjugated estrogens (n = 20), placebo (n = 20), or gabapentin titrated to 2,400 mg/d (n = 20) for 12 weeks. Participants recorded frequency and severity of baseline hot flushes on a hot flush diary for 2 weeks before randomization and for 12 weeks after randomization. The primary outcome measure was the weekly hot flush composite score, which takes into account both severity and frequency of hot flushes. Secondary outcome measures were differences in pre- and posttreatment scores pertaining to depression (Zung Depression Scale) and other climacteric symptoms (Greene Climacteric Scale). RESULTS: Intention-to-treat analysis showed that the reduction in the hot flush composite score for both estrogen (72%, P = .016) and gabapentin (71%, P = .004) was greater than the reduction associated with placebo (54%) at the conclusion of the 12th week. The extent of reduction in hot flush composite score, however, was not significantly different between estrogen and gabapentin (P = .63). No differences were seen between groups in the Zung Depression Scale, or in any of the Greene Climacteric subscales except for the Somatic Symptom cluster, which was significantly greater in the gabapentin arm than in the placebo arm. Despite a lack of group differences in adverse events, the Headache, Dizziness, and Disorientation cluster appeared with greater frequency in the gabapentin group. Estimation of the number needed to harm in this cluster suggests that these symptoms may occur with every fourth patient treated with gabapentin. CONCLUSION: Despite the small scale of this study, gabapentin appears to be as effective as estrogen in the treatment of postmenopausal hot flushes. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT 00276081. LEVEL OF EVIDENCE: I.

Amines↗
PubMed2005

Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: Gabapentin has been shown to reduce elements of central sensitization in human experimental hyperalgesia. It remains uninvestigated whether gabapentin has beneficial effects for irritable bowel syndrome associated with visceral hypersensitivity. AIMS: To evaluate the effects of gabapentin on sensory and motor function of the rectum in patients with diarrhoea-predominant irritable bowel syndrome. METHODS: Forty patients with diarrhoea-predominant irritable bowel syndrome completed this randomized, double-blind, placebo-controlled, parallel-grouped study. All patients received a barostat study and were subsequently randomized for 5-day treatment with gabapentin 300 mg/day and then 600 mg/day or placebo. On day 6, after subjects had their morning dose, the barostat experiment was repeated. RESULTS: The threshold pressures for bloating, discomfort and pain significantly increased after gabapentin, but not after placebo. Significant increase in the pressure and corresponding wall tension inducing discomfort or pain were observed in the gabapentin group, but not in the placebo group. Rectal compliance significantly increased after gabapentin, but not after placebo. The postprandial increase of rectal tone was not affected by gabapentin. CONCLUSION: Our results show that gabapentin reduces rectal sensory thresholds through attenuating rectal sensitivity to distension and enhancing rectal compliance in diarrhoea-predominant irritable bowel syndrome patients. The clinical efficacy of this drug in irritable bowel syndrome patients warrants investigation.

Adult↗
PubMed2006

The effect of gabapentin on post-operative pain following tonsillectomy in adults.

BACKGROUND: The aim of the present study was to investigate whether a combination of rofecoxib and gabapentin could improve pain relief and reduce opioid requirements, compared with rofecoxib alone, during the first 5 days after tonsillectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 49 patients received gabapentin 1200 mg pre-operatively, followed by gabapentin 2 x 600 mg on the day of operation and gabapentin 3 x 600 mg for the next 5 days, or placebo. Both groups were given rofecoxib 50 mg daily. In the post-operative care unit, intravenous morphine was administered in doses of 2.5 mg on request. From 4 h to 5 days post-operatively, ketobemidone was offered as escape drug. Pain at rest and during swallowing, and side-effects, were assessed using a four-point verbal rating scale. RESULTS: As a result of the global withdrawal of rofecoxib, the study had to be terminated prematurely. This report comprises the results from 22 patients in the gabapentin group and 27 patients in the placebo group. Gabapentin reduced ketobemidone requirements during the first 24 h post-operatively [4.5 mg (standard deviation, 3.0 mg) in the placebo group vs. 2.0 mg (standard deviation, 2.0 mg) in the gabapentin group; P < 0.003]. Gabapentin induced more dizziness (P < 0.002), gait disturbance (P < 0.02) and vomiting (P < 0.05) during days 0-5 than placebo. No other statistically significant differences were observed. CONCLUSION: Gabapentin reduced opioid requirements in the first 24 h after tonsillectomy. The benefits of the reduced opioid intake may be overshadowed by the drawbacks of side-effects.

Adolescent↗
PubMed2006

Treatment of partial seizures with gabapentin: double-blind, placebo-controlled, parallel-group study.

This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.

Adolescent↗
PubMed1999

Gabapentin in the management of convulsive disorders.

Gabapentin, in clinical use since 1993, is indicated as an adjunctive antiepileptic drug (AED) for treatment of complex partial seizures, with or without secondary generalization, in patients over 12 years of age. Although several cellular actions have been described in the literature, the molecular mechanism(s) of action responsible for the anticonvulsant effect of gabapentin has not been conclusively determined. It is likely that gabapentin has multiple concentration-dependent actions that combine in a unique manner to produce antiepileptic efficacy. The pharmacokinetic properties of this water-soluble, amino-acid AED are generally favorable. Absorption appears to be dependent on transport by the L-system amino acid transporter. Elimination of unmetabolized drug occurs by the renal route. Although its therapeutic range is not well characterized, gabapentin has a broad therapeutic index. This implies that a wide range of doses can be used, based on individual patient needs, without significant limitation due to dose-dependent side effects. Gabapentin has few drug-drug interactions, none of which is clinically limiting. Several studies have demonstrated the long-term efficacy of gabapentin with no systematic evidence of tachyphylaxis. In addition, there is increasing evidence to support the use of gabapentin as monotherapy. Gabapentin is safe and is generally well tolerated. To date, nearly 3 million patients have been treated in studies and in open use without causal relationship to a specific life-threatening organ toxicity. Seizure control superior to that observed in well-controlled trials has been reported at higher doses used in clinical practice and in studies. Therefore, gabapentin dosing must be optimized on an individual basis to achieve an adequate trial of the drug and obtain the best seizure control.

Acetates↗
PubMed2005

[Gabapentin for spasticity: a randomized, double-blind, placebo-controlled trial].

BACKGROUND AND OBJECTIVE: We aimed to demonstrate the efficacy and safety of gabapentin for the treatment of spasticity in patients with upper motor neuron syndrome. PATIENTS AND METHOD: Thirty patients with pyramidal-tract lesions were randomized to up to 3,600 mg/day of gabapentin (n = 15) or placebo (n = 15) in a double-blind, pilot 10-week trial. The primary efficacy variable was the Ashworth Scale score. Secondary variables included the Spasm Frequency Scale, maximal range of movement, H/M Amplitude Ratio, and the Barthel Index for quality of life. Adverse events were recorded. All data were analyzed on an intent-to-treat basis. RESULTS: Demographic and baseline characteristics were similar between the 2 treatment groups. The gabapentin group showed significant improvement in Ashworth Scale total scores, and scores for individual affected muscle groups. Fifteen of the randomized patients had spasms; the total Spasm Frequency Scale score was not significantly different between groups. Nevertheless, when affected individual muscle groups were analyzed, a significant effect of gabapentin vs placebo was observed at all visits. Gabapentin did not modify the scores of the range of movement, the H/M Amplitude Ratio, or the Barthel Index tests. No gait or displacement impairment were seen during treatment with gabapentin. Related adverse events occurred less frequently in the gabapentin group, and fewer gabapentin patients withdrew because of adverse events. CONCLUSIONS: Gabapentin demonstrated efficacy and safety at doses between 2,700 and 3,600 mg/day as a therapy for the spasticity associated with the upper motor neuron syndrome.

Adult↗
PubMed2002

Neurotransmitter mechanisms in gabapentin antinociception.

The present study was done to investigate the neurotransmitter mechanisms involved in gabapentin antinociception in healthy albino rats. The formalin test was used to asses antinociception. Gabapentin (10-120 mg/kg s.c.) decreased the pain score in the formalin test. In order to study the putative neurotransmitter mechanisms involved in gabapentin action, the effect of gabapentin (30 mg/kg s.c.) alone and in rats pretreated with different receptor blockers, e.g. bicuculine, saclofen, naloxone, mecamylamine, atropine, DL-p-chlorophenylalanine methyl ester hydrochloride, glibenclamide, theophylline, and L-arginine was assessed. Gabapentin decreased the pain score, and the ED(50) of gabapentin was 36.8 +/- 8.2 (30.2-43.1) mg/kg s.c. Pretreatment with different receptor blockers did not modify gabapentin (30 mg/kg s.c.) antinociception except for L-arginine which increased the pain score from 1.68 +/- 0.29 (gabapentin) to 2.29 +/- 0.41. Results suggest the involvement of L-arginine nitric oxide pathways in gabapentin antinociception.

Acetates↗
PubMed2006

Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5.

PURPOSE: Despite the utility of newer antidepressants for alleviating hot flashes, antidepressants do not work adequately enough in many patients. Gabapentin is a nonhormonal agent that also can reduce hot flashes. No data have been available to address whether the combination of both agents would more effectively alleviate hot flashes, compared with gabapentin alone, in patients with inadequate hot flash control with an antidepressant alone. PATIENTS AND METHODS: This was a randomized trial in which 118 patients with inadequate hot flash control on an antidepressant were randomly assigned to receive both an antidepressant and gabapentin versus being weaned off the antidepressant and receiving gabapentin alone. Patients were observed for 5 weeks (including a baseline week in which patients continued on their current antidepressant without gabapentin) during which time they completed validated daily hot flash diaries. RESULTS: Ninety-one patients provided complete data at the 5-week assessment. Regardless of whether or not the antidepressant was continued when gabapentin was started, there was an approximately 50% median reduction in hot flash frequencies (54%; 95% CI, 34% to 70% for combined treatment v 49%; 95% CI, 26% to 58% for gabapentin alone) and scores (56%; 95% CI, 26% to 71% for combined treatment v 60%; 95% CI, 33% to 73% for gabapentin alone). CONCLUSION: Gabapentin seems to decrease hot flashes by approximately 50% in women with inadequate hot flash control who were using an antidepressant. This study saw no significant additional hot flash reduction from continuation of the antidepressant.

Adult↗