OBJECTIVES

To describe and evaluate the evidence from randomized controlled clinical trials the efficacy and tolerability of pregabalin as add-on therapy for patients with refractory partial seizures.

METHODOLOGY

Medline/PubMed, Cochrane, Ovid, MdConsult, Google, Herdin, and ClinicalTrials.gov databases were searched to identify all randomized controlled clinical trials on the use of pregabalin as add on therapy for refractory seizures. Data were extracted on the basis of an intention-to-treat principle. Treatment effects were measured as odds ratios between pregabalin and placebo. Data were analyzed using the Review Manager 4.2 software. Pooled estimates (using a 95% confidence interval) were computed using the random effects model. Study endpoints used were responder rates, seizure freedom, rates of adverse events, and discontinuation rates due to lack of efficacy and adverse events.

RESULTS

Four eligible randomized controlled trials comprising 1397 patients were included. Statistically significant responder rates (pooled OR 5.16; 95% Cl 3.27-8.13, p < 0.00001) in favor of pregabalin were demonstrated, with greater responder rates noted with increasing pregabalin doses. A trend towards seizure freedom in favor of pregabalin was also noted but statistically insignificant (pooled OR 1.21; 95% Cl 0.74-1.98, p = 0.45). Add-on pregabalin resulted in the occurrence of treatment-related adverse events (pooled OR 25.18; 95% Cl 8.88-71.44, p < 0.0001) but did not result in a statistically significant discontinuation (pooled OR 1.86; 95% Cl 0.98-3.54, p = 0.06). Adverse events were mild to moderate in severity and were generally well tolerated.

CONCLUSION

Add-on pregabalin is an effective and fairly tolerable adjunctive therapy for the treatment of patients with refractory partial seizures.

Human ; Pregabalin ; ; Nervous System Diseases

BACKGROUND

In spite of major recent advances in the treatment of aneurysmal subarachnoid hemorrhage (SAH), management of cerebral vasospasm and its consequences still remain a formidable clinical challenge. Magnesium may exhibit a range of vascular and neuronal actions that may ameliorate ischemic central nervous system insults.

OBJECTIVES

(1) To determine whether i ntravenous magnesium therapy in addition to standard care can improve functional outcome in patients with aneu rysmal SAH. (2) To determine whether intravenous magnesium therapy in addition to standard care can reduce the frequency of symptomatic vasospasm.

METHODOLOGY

Medline, Cochrane, Ovid, Stroke Group Trial Register and Herdin databases were searched to identify all randomized controlled trials on the use of intravenous magnesium therapy in addition to standard care versus standard care alone in patients with aneurysmal SAH. The studies were analyzed using the Review Manager 4.2 software. An estimate of the treatment effect across trials were measured using relative risks (with a 95% confidence interval) and were pooled using random effects.

RESULTS

Three studies involving 379 patients were included. Overall, the relative risk of intravenous magnesium therapy for poor outcome was 0.75 (95% Cl, 0.57 - 1 .0). Although there was a trend to favor the treatment group, it did not reach statistical significance. The risk of intravenous magnesi um therapy on the occurrence of symptomatic vasospasm was significantly reduced, with a RR of 0.66 (95% Cl, 0.45-0.96).

CONCLUSION

I ntravenous magnesi um therapy as adj unct to standard care in patients with aneurysmal SAH shows a trend favoring treatment with a significant reduction in symptomatic vasospasm but not enough evidence to support its effect on improving over-all functional outcome.

Human ; Subarachnoid Hemorrhage, Aneurysmal ; Subarachnoid Hemorrhage ; Cerebral Vasospasm ; Vasospasm, Intracranial

OBJECTIVES

To describe and evaluate the evidence from major randomized controlled clinical trials investigating the efficacy and tolerability of pregabalin as add-on therapy for patients with refractory partial epilepsy.

METHODOLOGY

Medline/PubMed, Cochrane, Ovid, Md Consult, Google, and Herdin databases were searched to identify all randomized controlled clinical trials on the use of pregabalin as add-on therapy for refractory epilepsy. The data from the relevant trials was extracted on the basis of an intention-to-treat principle. Treatment effects were measured as odds ratios between pregabalin and placebo. Tests for heterogeneity was done using the Mantel-Haenszel method. Pooled estimates ( using a 95% confidence interval) were computed according to the random effects model. Efficacy measures or study endpoints used were responder rates, degree of seizure freedom, and frequency of treatment-related adverse events.

RESULTS

Four eligible randomized controlled trials, involving a total of 1 379 patients, were included in the study. The combmed odds ratio for the responder rate was 7.28 (95% CI 4.42-11 .98) in favor of add-on pregabalin therapy versus placebo, the treatment effect of which was noted to be statistically significant (p < 0.00001). Higher responder rates were noted with higher pregabalin doses. The most common adverse events during the treatment period were dizziness, somnolence, ataxia, and weight gain. The majority of adverse events was mild to moderate in intensity and is generally well tolerated. The combined odds ratio for seizure freedom was 1 .72 (95% CI 0.84-3.53) in favor of pregabalin, the treatment effect of which is, however, not statistically significant (p = 0. 1 4).

CONCLUSION

Pregabalin is an effective and fairly tolerable adjunctive therapy for the treatment of for patients with refractory focal seizures.

Human ; Pregabalin ; Epilepsies, Partial ; Drug Resistant Epilepsy