AUStralian Study of Titration to Effect Profile of Safety (AUS‐STEPS): High‐Dose Gabapentin (Neurontin) in Partial Seizures

Abstract

Summary:Purpose:To evaluate the safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin; GBP) as adjunctive therapy in patients with refractory partial seizures.Methods: AUS-STEPS was an open-label, multicenter, prospective study in patients experiencing partial seizures who were inadequately controlled with one to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrated to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to achieve an efficacious and tolerable dosage. Efficacy was assessed by seizure-frequency data. Quality of life was evaluated by using the QOLIE-10 questionnaire, and safety was assessed by adverse-event reports and clinical laboratory findings.Results: A total of 176 patients received treatment with GBP, with 174 evaluable for intention-to-treat (ITT) efficacy analysis. A reduction of >50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE-10 score. The most frequent adverse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events necessitating discontinuation as the dose of GBP was titrated upward.Conclusions. This study indicates that patients with partial epilepsy may be effectively treated with GBP at dosages of ഛ4,800 mg/day, without altering the safety profile of the drug.

Justification for conducting neurological clinical trials as part of patient care within private practice

“…SHE also performed in‐house research, as evidenced by: review of pharmacokinetics ; management of headache ; audit of Sudden Unexplained Death in Epilepsy ; association of ulcerative colitis and MS ; the role of AEM blood levels to determine the cause of medication toxicity ; assessing the usefulness of levetiracetam (LEV) drug levels in treating epilepsy and reviewing anti‐epileptic medication (AEM) blood levels . SHE also has been the principal site for trials in collaboration with large academic institutions .…”

“…It has been argued that clinical trials have been manipulated to be little more than marketing strategies, especially with gabapentin , in which Phase IV studies have been used to encourage investigators to initiate a medication which they may have otherwise not used. The opposite has been the case with gabapentin and SHE, as SHE had to argue forcefully to establish investigator‐initiated gabapentin trials that were neither developed, nor advocated by the responsible pharmaceutical company and produced results that questioned the accepted wisdom at that time . It remains imperative to place the interests of patients above all other considerations.…”

Association of HMG-CoA Reductase Inhibitors with Neuropathy

“…The safety of gabapentin is well established in doses as high as 4800 mg/d. 26 Among the most common adverse effects are somnolence and dizziness, which tend to be transient. 27, 28 Our review of…”

Gabapentin for the Treatment of Tremor

“…The safety of gabapentin is well established in doses as high as 4800 mg/d. 26 Among the most common adverse effects are somnolence and dizziness, which tend to be transient. gabapentin use in tremor revealed a single serious adverse event (a fall with head injury) that occurred in a patient taking placebo.…”