Gabapentin for Neuropathic Pain: Systematic Review of Controlled and Uncontrolled Literature

ObjectiveTo assess the efficacy/effectiveness and side effects of gabapentin for the treatment of neuropathic pain. DesignSystematic review of the literature. MethodsExtensive search of several electronic databases located both controlled and uncontrolled studies. Efficacy was assessed through meta-analysis of randomized controlled trials (RCTs), whereas the effectiveness of gabapentin in uncontrolled studies was assessed via a novel system of dichotomous classification of “bad” versus “good” results. FindingsThirty-five papers involving 727 patients with multiple neuropathic pain conditions met the inclusion criteria. The meta-analysis of the 2 high-quality, placebo-controlled RCTs showed positive effect of gabapentin in diabetic neuropathy and post-herpetic neuralgia. The addition of 2 low-quality, placebo-controlled RCTs did not alter the magnitude or direction of observed effect. The uncontrolled studies demonstrated positive effect on pain in different neuropathic syndromes, as well as benefit on different types of neuropathic pain; highest dose administered and rate-of-dose escalation showed wide variability between prescribers. Fewer and less severe side effects were reported in the uncontrolled studies. ConclusionsGabapentin seems to be effective in multiple painful neuropathic conditions. The variable prescribing patterns of the uncontrolled studies raise the suspicion that effectiveness may be reduced if one limits administration of the drug to very low doses, whereas rapid dose escalation may be associated with increased central nervous system side effects. Well-designed controlled trials may provide insight into differential symptom sensitivity to the drug.

[1]  P. Mazzarello,et al.  Gabapentin vs. amitriptyline in painful diabetic neuropathy: an open-label pilot study. , 2000, Journal of pain and symptom management.

[2]  J. Fudin,et al.  Gabapentin vs amitriptyline for the treatment of peripheral neuropathy. , 2000, Archives of internal medicine.

[3]  M. Backonja Managing painful diabetic neuropathy. , 1999, Hospital practice.

[4]  S. Leckband,et al.  Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. , 1999, Archives of internal medicine.

[5]  A. Beydoun,et al.  Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients With Diabetes Mellitus: a Randomized Controlled Trial , 1999 .

[6]  J. Ebbert,et al.  Gabapentin for painful diabetic neuropathy. , 1999, JAMA.

[7]  E. Zecca,et al.  Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain. , 1999, Journal of pain and symptom management.

[8]  C. Otley Gabapentin for the treatment of dysesthetic pain after reconstructive surgery. , 1999, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[9]  H. Hays Query "wind-down, switch-off". , 1999, Journal of pain and symptom management.

[10]  J. Eisenach,et al.  Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats. , 1999, The Journal of pharmacology and experimental therapeutics.

[11]  S. McCleary,et al.  Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat , 1999, Pain.

[12]  M. Lema,et al.  Acute herpetic neuralgia and postherpetic neuralgia in the head and neck: response to gabapentin in five cases. , 1999, Regional anesthesia and pain medicine.

[13]  J. Bryans,et al.  3‐Substituted GABA analogs with central nervous system activity: A review , 1999, Medicinal research reviews.

[14]  Seidl Jj,et al.  Gabapentin for painful diabetic neuropathy. , 1999 .

[15]  W. Rand,et al.  Gabapentin in the treatment of painful diabetic neuropathy: a placebo controlled, double blind, crossover trial , 1999, Journal of neurology, neurosurgery, and psychiatry.

[16]  M. Rowbotham,et al.  Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. , 1998, JAMA.

[17]  Salahadin Abdi,et al.  The Anti-Allodynic Effects of Amitriptyline, Gabapentin, and Lidocaine in a Rat Model of Neuropathic Pain , 1998, Anesthesia and analgesia.

[18]  B. Stacey,et al.  Gabapentin for treatment of neuropathic pain in a 12-year-old girl. , 1998, The Clinical journal of pain.

[19]  D. Gavaghan,et al.  Size is everything – large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects , 1998, Pain.

[20]  L. Sorkin,et al.  Systemic gabapentin and S(+)-3-isobutyl-γ-aminobutyric acid block secondary hyperalgesia , 1998, Brain Research.

[21]  J. Mountz,et al.  A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin , 1998, Pain.

[22]  D. Bouhassira,et al.  Effects of Gabapentin on the Different Components of Peripheral and Central Neuropathic Pain Syndromes: A Pilot Study , 1998, European Neurology.

[23]  M. D. Merren Gabapentin for Treatment of Pain and Tremor: A Large Case Series , 1998, Southern medical journal.

[24]  O. Khan Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients , 1998, Neurology.

[25]  A. Uccelli,et al.  An open-lebel trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients , 1998, Neurology.

[26]  M. Childers,et al.  The Use of Gabapentin for Neuropathic and Musculoskeletal Pain: A Case Series , 1998 .

[27]  S. Carlton,et al.  Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin , 1998, Pain.

[28]  S Sánchez-Valiente,et al.  [Treatment of neuropathic pain with gabapentin ++]. , 1998, Revista de neurologia.

[29]  T. Yaksh,et al.  The Effect of Intrathecal Gabapentin and 3-Isobutyl gamma-Aminobutyric Acid on the Hyperalgesia Observed After Thermal Injury in the Rat , 1998, Anesthesia and analgesia.

[30]  G. Newshan HIV neuropathy treated with gabapentin. , 1998, AIDS.

[31]  T. Yaksh,et al.  Characterization of the Effects of Gabapentin and 3‐Isobutyl‐gamma‐Aminobutyric Acid on Substance P‐induced Thermal Hyperalgesia , 1998, Anesthesiology.

[32]  A. Dickenson,et al.  Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats , 1998, Pain.

[33]  L. Sorkin,et al.  Gabapentin Reverses the Allodynia Produced by the Administration of Anti-GD2 Ganglioside, an Immunotherapeutic Drug , 1998, Anesthesia and analgesia.

[34]  E. Lucier,et al.  Use of gabapentin in a case of facial neuritis. , 1997, Anesthesia and analgesia.

[35]  A. Mailis,et al.  Drug interactions in human neuropathic pain pharmacotherapy , 1997, Pain.

[36]  R. Werner,et al.  The effect of gabapentin on neuropathic pain. , 1997, The Clinical journal of pain.

[37]  S. McCleary,et al.  Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. , 1997, The Journal of pharmacology and experimental therapeutics.

[38]  S. McCleary,et al.  Gabapentin (neurontin) and S‐(+)‐3‐isobutylgaba represent a novel class of selective antihyperalgesic agents , 1997, British journal of pharmacology.

[39]  J. Richert,et al.  Open label gabapentin treatment for pain in multiple sclerosis , 1997, Multiple sclerosis.

[40]  B. Koppel,et al.  Amelioration of refractory dysesthetic limb pain in multiple sclerosis by gabapentin , 1997, Neurology.

[41]  M. Lema,et al.  Gabapentin for idiopathic trigeminal neuralgia , 1997, Neurology.

[42]  T. Yaksh,et al.  Effect of Subarachnoid Gabapentin on Tactile‐Evoked Allodynia in a Surgically Induced Neuropathic Pain Model in the Rat , 1997, Regional anesthesia.

[43]  P. Kosek,et al.  Erythromelalgia pain managed with gabapentin. , 1997, Anesthesiology.

[44]  J. Hunter,et al.  The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. , 1997, European journal of pharmacology.

[45]  M. Lema,et al.  Experience With Gabapentin for Neuropathic Pain in the Head and Neck: Report of Ten Cases , 1997, Regional Anesthesia & Pain Medicine.

[46]  A. Dickenson,et al.  Gabapentin, ineffective in normal rats, markedly reduces C‐fibre evoked responses after inflammation , 1997, Neuroreport.

[47]  C. Pozzilli,et al.  Pain in Guillain-Barré syndrome , 1997, Neurology.

[48]  S. Schachter,et al.  Correlation between prevalence of interictal headaches among patients with epilepsy and antiepileptic drug regimen , 1996 .

[49]  G. Rordorf,et al.  Gabapentin as a novel treatment for postherpetic neuralgia , 1996, Neurology.

[50]  A. Jadad,et al.  The importance of quality of primary studies in producing unbiased systematic reviews. , 1996, Archives of internal medicine.

[51]  H. Rosner,et al.  Gabapentin adjunctive therapy in neuropathic pain states. , 1996, The Clinical journal of pain.

[52]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[53]  L. Mellick,et al.  Gabapentin in the management of reflex sympathetic dystrophy. , 1995, Journal of pain and symptom management.

[54]  G. Satzinger Antiepileptics from gamma-aminobutyric acid. , 1994, Arzneimittel-Forschung.

[55]  A. Furlan,et al.  Are we paying a high price for surgical sympathectomy? A systematic literature review of late complications. , 2000, The journal of pain : official journal of the American Pain Society.

[56]  J. Marco Algarra,et al.  [Use of gabapentin in glossopharyngeal neuralgia]. , 1999, Acta otorrinolaringologica espanola.

[57]  T. Ness,et al.  Case report on gabapentin. , 1998, Regional anesthesia and pain medicine.

[58]  M. Inglese,et al.  An open-label trial of gabapentin treatment of paroxysmal symptoms in multiple sclerosis patients. , 1998, Neurology.

[59]  L. Sorkin,et al.  Systemic gabapentin and S(+)-3-isobutyl-gamma-aminobutyric acid block secondary hyperalgesia. , 1998, Brain research.

[60]  L. Mellick,et al.  Reflex sympathetic dystrophy treated with gabapentin. , 1997, Archives of physical medicine and rehabilitation.

[61]  C. Taylor Mechanisms of action of gabapentin. , 1997, Revue neurologique.

[62]  J. J. Zapp Postpoliomyelitis pain treated with gabapentin. , 1996, American family physician.

[63]  C. Taylor Gabapentin: mechanisms of action , 1995 .

[64]  L. Mellick,et al.  Successful treatment of reflex sympathetic dystrophy with gabapentin. , 1995, The American journal of emergency medicine.