Efficacy and safety of alcohol reduction pharmacotherapy according to treatment duration in patients with alcohol dependence or alcohol use disorder: A systematic review and network meta-analysis.

BACKGROUND AND AIMS: Relapse is common in alcohol dependence (AD) and alcohol use disorder (AUD), so alcohol reduction therapy should be measured over as long a period as possible; however, existing reviews do not consider the duration of treatment and therefore alcohol reduction therapy may not have been appropriately evaluated. This review evaluated the efficacy and safety of alcohol reduction pharmacotherapy in patients with AD or AUD according to the duration of treatment. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that assessed 15 pharmacological agents. MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov and the International Clinical Trials Registry Platform were searched for eligible trials through to May 2021. Outcomes were heavy drinking days (HDD), total alcohol consumption (TAC), any adverse event and days without drinking. RESULTS: Fifty-five RCTs (n = 8891) were included. Nalmefene was superior to placebo for reducing HDD (standard mean difference [SMD] -0.28, 95% confidence interval [CI] -0.37, -0.18) and TAC (SMD -0.25, 95% CI -0.35, -0.16) in the long-term, but not in the short-term. Topiramate was superior to placebo for reducing HDD (SMD -0.35, 95% CI -0.59, -0.12) and days without drinking (SMD 0.46, 95% CI 0.11, 0.82), and baclofen was superior for reducing TAC (SMD -0.70, 95% CI -1.29, -0.11), in the short-term. The frequency of adverse events was higher with nalmefene and topiramate than with placebo. CONCLUSION: Nalmefene, topiramate and baclofen may be effective as alcohol reduction pharmacotherapy; however, only nalmefene has demonstrated long-term efficacy, and nalmefene and topiramate have a significantly higher frequency of adverse events compared with placebo.

Lamotrigine in the maintenance treatment of bipolar disorder.

BACKGROUND: Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall functioning and health-related quality of life.  A worldwide prevalence rate of 2.4% has been reported. The risk of suicide is higher in people with bipolar disorder than those with other mental disorders. Therefore, effective management of bipolar disorder in the maintenance period is warranted to minimize the risk of relapse or recurrence. Although lithium has been the standard treatment of bipolar disorder for many years, it is associated with adverse effects and teratogenicity. Lamotrigine is approved to be expected for prevention of recurrence for the maintenance treatment of bipolar disorder. In addition, lamotrigine is as effective as lithium. Therefore, we performed a systematic review to confirm the efficacy and safety of lamotrigine in the maintenance treatment of bipolar disorder. OBJECTIVES: To assess the efficacy and tolerability of lamotrigine in the maintenance treatment of bipolar disorder. SEARCH METHODS: We searched Ovid MEDLINE, Embase, PsycINFO, the Cochrane Common Mental Disorders Group's Specialized Register (CCMDCTR) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 21 May 2021. We also searched international trial registries and contacted experts in the field. SELECTION CRITERIA: We included randomized controlled trials enrolling adults with bipolar disorder who were treated with lamotrigine, placebo or lithium. DATA COLLECTION AND ANALYSIS: Two reviews authors independently checked the eligibility of studies and extracted data using a standardized form. Data extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in the term of efficacy and tolerability. Study information were then entered into RevMan web. MAIN RESULTS: We included 11 studies with a total of 2314 participants in this review; 1146 were randomized to lamotrigine, 869 were randomized to placebo and, 299 to lithium. We rated all studies as having an unclear risk of bias in at least one domain of Cochrane's tool for assessing risk of bias, with the most commonly observed weakness being selection bias (random sequence generation and allocation concealment). We judged five studies to be at a high risk of detection bias (blinding of outcome assessment). These potential biases pose as major threat to the validity of the included studies in this review. Outcomes of efficacy showed a possible advantage of lamotrigine over placebo. The estimated risk ratio (RR) for recurrence of manic symptom at one year as measured by the Young Mania Rating Scale (YMRS) was 0.67, (95% confidence interval (CI) 0.51 to 0.87; 3 studies, 663 participants; low-certainty evidence) in favor of lamotrigine. The RR of clinical worsening with the need for additional psychotropic treatment (RR 0.82, 95% CI 0.70 to 0.98; 4 studies, 756 participants) based on moderate-certainty evidence. The possible benefits of lamotrigine were also seen for the outcome of treatment withdrawal due to any reason at 6-12 months after treatment (RR 0.88, 95% CI 0.78 to 0.99; 4 studies, 700 participants; moderate-certainty evidence). Regarding tolerability, our analyses showed that the incidence rates of adverse effects were similar between the lamotrigine group and the placebo group (short-term effect: RR 1.07, 95% CI 0.81 to 1.42; 5 studies, 1138 participants; very low-certainty evidence; long-term effect: RR 0.97, 95% CI 0.77 to 1.23; 4 studies, 756 participants; moderate-certainty evidence). In the comparison between lamotrigine and lithium, efficacy was similar between groups except for recurrence of mania episode at one year. Recurrence of manic symptoms was higher in the lamotrigine group than that of the lithium group (RR 2.13, 95% CI 1.32 to 3.44; 3 studies, 602 participants; moderate-certainty evidence). Analysis of adverse effects at 6-12 months showed that a lower proportion of participants experienced at least one adverse effect when treated with lamotrigine compared to lithium (RR 0.70, 95% CI 0.51 to 0.96; 4 studies, 691 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Low- to moderate-certainty evidence collectively suggests that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder. In comparison to lithium, people with bipolar disorder seem to tolerate lamotrigine better in the long run; however, the demonstrated efficacy in the maintenance of bipolar disorder was similar between the two groups.

Effects of a conventional mood stabilizer alone or in combination with second-generation antipsychotics on recurrence rate and discontinuation rate in bipolar I disorder in the maintenance phase: A systematic review and meta-analysis of randomized, placebo-controlled trials.

OBJECTIVES: A systematic review and meta-analysis of double-blind, randomized placebo-controlled trials were conducted to examine how soon an increase in recurrence risk could be observed among bipolar I disorder (BDI) patients who were clinically stable with the combination therapy of mood stabilizers with second-generation antipsychotics (SGA+MS) treatment following second-generation antipsychotics discontinuation (i.e., MS alone) compared with SGA+MS maintenance. METHODS: Embase, PubMed, and CENTRAL databases were used for systematic literature searches until May/22/2020. The primary outcome was the recurrence rate of any mood episode at 6 months. The secondary outcomes were the recurrence rates of manic/hypomanic/mixed and depressive episodes and all-cause discontinuation at 6 months. The recurrence rates at 1, 2, 3, 9, and 12 months were also investigated. RESULTS: Eight studies (mean study duration = 58.25 ± 33.63 weeks) were identified (SGA+MS group [n = 1,456: 3 aripiprazole+MS studies, 1 lurasidone+MS study, 1 olanzapine+MS study, 2 quetiapine+MS studies, 1 ziprasidone+MS study] and placebo+MS group [n = 1,476]). Pooled SGA+MS exhibited lower recurrence rates of any mood episode, manic/hypomanic/mixed episodes, and depressive episodes as well as reduced all-cause discontinuation at every observational point. The risk ratios (95% confidence interval) of the recurrence rate at 6 months were 0.51 (0.39-0.86) for any mood episode, 0.42 (0.30-0.59) for manic/hypomanic/mixed episodes, and 0.39 (0.28-0.54) for depressive episodes. The RR for all-cause discontinuation was 0.67 (0.50-0.89). Both aripiprazole+MS and quetiapine+MS outperformed placebo+MS in the recurrence of any mood, manic/hypomanic/mixed, and depressive episodes at 6 months. CONCLUSIONS: SGA+MS prevented recurrence for up to 12 months for BDI compared with placebo+MS.

Recurrence of Mania or Depression Among Adult Bipolar Patients Who Continued Using Lithium: A Single-group Summary Meta-analysis of Randomized Trials.

BACKGROUND: The exact recurrence rate of bipolar disorder in patients receiving lithium maintenance phase treatment and the modifiers associated with recurrence are still unknown. METHODS: We searched Embase, PubMed, and CENTRAL from inception until April 28, 2020. Outcomes included recurrence rate of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes; all-cause discontinuation rate; and discontinuation rate due to adverse events. A random-effects model, single-group summary meta-analysis was conducted. A meta-regression analysis to examine whether the modifiers (total number of patients, %female, mean age, duration of study, duration of preliminary phase, publication year, bipolar disorder type, mood status at recruitment, presence of a placebo arm, sponsorship, enrichment design, number of treatment arms, and risk of bias for blinding or randomization) were associated with the event rate of the outcomes was also performed. RESULTS: We identified 21 randomized trials (n = 1,415; mean study duration, 78.40 ± 32.10 weeks; %female, 54.85%; mean age, 43.47 ± 4.88 years). The event rates (95% confidence interval [CI]) were as follows: recurrence of any mood episode, 39.8% (32.8%, 47.1%); depressive episodes, 25.6% (18.8%, 34.0%); manic/hypomanic/mixed episodes, 18.5% (13.7%, 24.7%); all-cause discontinuation rate, 67.0% (57.2%, 75.5%); and discontinuation rate due to adverse events, 8.7% (5.1%, 14.7%). After adjusting for multiple testing, our meta-regression analysis showed association only between the all-cause discontinuation rate and presence of a placebo arm. CONCLUSIONS: The recurrence rate of depressive episodes seemed to be higher than the recurrence rate of manic/hypomanic/mixed episodes. The all-cause discontinuation rate was high. However, the studies included in our meta-analysis were of short duration.

Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder: A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials with an enrichment design.

AIM: Whether patients with adult bipolar disorder (BD) who have been clinically stabilized with lithium or lamotrigine should continue this medication is not established fully. This systematic review and meta-analysis evaluated the efficacy and safety of lithium and lamotrigine for maintenance treatment in clinically stable patients with adult BD. METHODS: This meta-analysis included only double-blind, randomized, placebo-controlled trials with an enrichment design that selected patients who responded acutely to lithium or lamotrigine. Reports prior to November 15, 2018, were retrieved from the PubMed/Cochrane Library/Embase. The primary outcome was the relapse rate due to any mood episode at the study endpoint. Other outcomes were relapse rates due to a manic/hypomanic/mixed episode or depression at the study endpoint, discontinuation rate, death, and death by suicide. Risk ratios (RRs) (95% confidence intervals) were calculated. When the random-effects model showed significant differences between groups, the number-needed-to-treat (NNT) was estimated. RESULTS: The search retrieved two studies regarding lithium (N = 218) and four evaluating lamotrigine (N = 706). Both drugs were superior to placebo for reducing the relapse rate due to any mood episode [lithium: RR = 0.52 (0.41-0.66), P < 0.00001, I2  = 0%, NNT = 2.3 (1.6-4.2); lamotrigine: RR = 0.81 (0.70-0.93), P = 0.004, I2  = 0%, NNT = 8.3 (5.0-25.0)] and all-cause discontinuation. There were no significant differences in other outcomes between lithium or lamotrigine and the placebo groups. CONCLUSION: Both drugs showed benefit for preventing relapse in clinically stable patients with adult BD. However, the number of studies and patients in this analysis was small.

Effect of pharmacist intervention on physician prescribing in patients with chronic schizophrenia: a descriptive pre/post study.

BACKGROUND: Although pharmacotherapy is one of the most important treatments for schizophrenia, the prominent levels of antipsychotic polypharmacy and high-dose regimens used in Japan are thought to be inconsistent with treatment regimens used in other countries. In this study, we evaluated the effect of pharmacist intervention on physician prescribing in patients with chronic schizophrenia. METHODS: Participants comprised 52 inpatients at Sawa Hospital (Osaka, Japan), treated with at least one antipsychotic agent, who received pharmacist intervention for 1 year (2012). We compared the dose and the number of antipsychotics prescribed, and the rate of concurrent prescribing of anti-Parkinson, benzodiazepine and mood-stabilizer medication, pre- and post-pharmacist intervention. As an indicator of psychosis symptoms, the rate of seclusion room use was recorded. Additionally, we evaluated the impact of pharmacist intervention on medicine costs. Continuous variables were analyzed by Wilcoxon signed-rank sum tests, and categorical data were analyzed using Fisher's exact tests. RESULTS: Compared with pre-intervention, the dose (982.6 mg pre vs. 857.6 mg post; p < 0.01) and the number of antipsychotics (2.0 pre vs. 2.0 post; p < 0.05) at 1 year were significantly lower post-intervention. The seclusion room use rate was not significantly different but tended to be lower post-intervention than pre-intervention (p < 0.1). The cost (in USD) for all medicines (10.33 pre vs. 8.76 post; p < 0.05), antipsychotics (8.04 pre vs. 6.48 post; p < 0.05), and psychotropics (9.24 pre vs. 7.68 post; p < 0.01) were significantly lower post-intervention than pre-intervention. CONCLUSION: Pharmacist intervention has the potential to optimize medication prescribing and reduce medication costs in patients with chronic schizophrenia. It might be suggested that clinical practitioners as well as medical hospital administrators consider the pharmacists' ability to rationalize medication therapy in schizophrenia.

The need for educating patients with schizophrenia about the adverse effects of medications.

OBJECTIVE: Medication non-adherence is observed in many patients with schizophrenia. We investigated the effects of educational intervention on patient awareness of the adverse effects of their medication for patients with schizophrenia. METHODS: Inpatients with schizophrenia (N=87) in two Japanese hospitals were allocated to two groups, one that was aware of the adverse effects of medications and one that was unaware, according to their responses to the question 'In the past month, have you experienced any adverse effects from your medications?' Then, they were questioned about adverse effects. RESULTS: Only 27.6% of patients recognized the adverse effects of their medications. After pharmacists educated them and showed them a list of adverse effects, the prevalence of recognition increased dramatically (≤96.6%). Most patients with schizophrenia clearly did not recognize the adverse effects of their medications. When patients experienced discomfort they tended to stop taking their medications. CONCLUSIONS: Adverse effects are a common risk factor for discontinuation of medication, so early detection and reporting of such effects may result in them being addressed sooner. Considering the risks of relapse caused by discontinuation of medication, healthcare professionals should actively educate patients with schizophrenia about dysphoria and manage adverse effects.

Effects of antipsychotic polypharmacy on side-effects and concurrent use of medications in schizophrenic outpatients.

AIMS: Medical therapy is the cornerstone of schizophrenia, but >50% of patients do not adhere to medication regimens. In previous reports, the reasons for non-adherence were assessed only by medical staff. We think that patients have specific reasons for non-adherence. We researched whether there was an association between patients' subjective opinions and the number of antipsychotics used. METHODS: A self-rating questionnaire survey was conducted on 252 outpatients with schizophrenia at five psychiatric hospitals in Japan. Based on patients' subjective opinions, we retrospectively analyzed the patients' medications: the number of antipsychotics, concurrently used agents, and dosages of antipsychotics. RESULTS: There was no significant difference regarding attitudes toward medication between monotherapy and polypharmacy. The most common reason for not taking medications was 'I sometimes forget' followed by 'side-effects'. Of the latter, weight gain was the most common, and dry mouth (P < 0.05) and sexual dysfunction (P < 0.01) were significantly higher in polypharmacy. The dosages of antipsychotics (P < 0.01), concurrent use of anti-Parkinsonian agents (P < 0.01), and the number of side-effects (P < 0.01) were also higher in polypharmacy. CONCLUSIONS: Patients had good attitudes toward medication but a higher prevalence of side-effects was seen in polypharmacy of antipsychotics. Hence, monotherapy may be a more appropriate prescription with respect to side-effects. By using monotherapy, patients may reduce feelings of discomfort due to side-effects.

Effects of drugs acting on the GABA-benzodiazepine receptor complex on flurothyl-induced seizures in Mongolian gerbils.

In the present study, the mechanism behind flurothyl-induced seizures was examined using drugs acting on the GABA-benzodiazepine receptor complex in Mongolian gerbils. In addition, amino acid concentrations in the brain were also investigated. In behavioral experiments, the incidence of tonic extensor was 83.3% in both the control and picrotoxin (0.5 mg/kg)-treated groups, 0% in the valproate (200 mg/kg)-treated group, and 50% in the picrotoxin plus valproate-treated group. However, picrotoxin did not antagonize the effect of valproate on clonic seizure latency at all. Flumazenil, a benzodiazepine receptor antagonist, was found to have an inhibitory effect on the anticonvulsant action of diazepam (0.5 mg/kg). The incidence of tonic extensor was 83.3% in flumazenil (10 mg/kg)-treated group, 0% in the diazepam (0.5 mg/kg)-treated group, and 83% in the flumazenil plus diazepam-treated group as well as the control group. Flumazenil also completely reversed the effect of diazepam on clonic seizure latency. In biochemical experiments, the concentration of the inhibitory amino acid, GABA, was significantly increased in the hippocampus (P<0.05) and cerebellum (P<0.01) in diazepam-treated animals. The increase of GABA in the hippocampus and cerebellum was antagonized by the administration of flumazenil. These results suggested that the anticonvulsant action of diazepam may be linked to increase in hippocampus and cerebellum GABA concentrations. The findings suggest that the mechanism of flurothyl-induced seizures, in part, is related to the highly sensitive benzodiazepine site of the GABA-benzodiazepine receptor complex.

[A sheared off and sequestered epidural catheter: a case report].

This is a report of a retained epidural catheter segment after placement of 20-G polyethylene catheter (Hakko Medical) through 17-G Tuohy needle and 25-G spinal needle (Top Company) for a patient receiving combined spinal-epidural anesthesia. Retained catheter fragment (approximately 10.6 cm) was removed easily with small incision under local anesthesia. Electron microscopic findings of the catheter showed that the catheter might have been traumatized by the Tuohy needle through which the catheter was placed or by the spinal needle for intrathecal anesthesia, resulting in having been sheared off.

Cessation of repeated administration of MK-801 changes the anticonvulsant effect against flurothyl-induced seizure in mice.

The effects of acute and repeated administration of MK-801 on flurothyl (FE)-induced seizure were investigated in mice. In the acute effect of MK-801 (0.01-0.1 mg/kg ip) in naive and FE-kindled mice, there were no changes on the latencies of clonic seizures. However, MK-801 dose-dependently inhibited both latencies and incidence of tonic seizures in mice and suppressed the grade of seizure severity in FE-kindled mice. Repeated administration of MK-801 at doses of 0.01 and 0.1 mg/kg 2 h prior to each exposure to FE for 8 days did not show any effects on the latencies of clonic seizure. However, seizure severity was significantly exacerbated in the 0.1 mg/kg treated group when mice were re-exposed to FE without MK-801 1 week after the last administration. A week after the repeated administration of MK-801 at a dose of 0.1 mg/kg for 8 days without exposure to FE, mice were exposed to FE 2 h after readministration of MK-801 until tonic seizure occurred. The latencies of clonic seizures were almost the same in the acute experiment in naive controls. The latency of tonic seizure was significantly delayed compared to the acute experiment with MK-801 at a dose of 0.1 mg/kg. These findings suggested that MK-801 possessed an anticonvulsant action against FE-induced tonic seizure. However, the efficacy of this acute effect of MK-801 was impaired at 1 week of withdrawal after repeated administrations. This may be related in part to the changes in sensitivity to NMDA receptors.

Effects of valproate, phenytoin, and zonisamide on clonic and tonic seizures induced by acute and repeated exposure of mice to flurothyl.

The effects of valproate (VPA), zonisamide (ZNS), and phenytoin (PHT) on flurothyl (FE)-induced generalized seizure were investigated in mice. In the FE kindling model, eight daily FE-induced generalized clonic seizures followed by a 28-day stimulation-free interval converted the type of seizure expressed in response to FE from clonic to tonic. In an acute FE trial experiment, the latencies of clonic and tonic seizures were prolonged significantly and dose-dependently by the administration of VPA. ZNS and PHT did not show any effect on the latencies of tonic seizure. When the same three drugs were administered to mice daily for 8 days prior to the FE trial, changes in the seizure phenotypes from clonic to tonic seizure were significantly inhibited by VPA and ZNS, but not by PHT. These results suggest that VPA and ZNS possess significant antiepileptogenic properties. PHT apparently does not share this property to the same degree in the present FE-induced model.

Characteristics of flurothyl-induced seizures and the effect of antiepileptic drugs on flurothyl-induced seizures in Mongolian gerbils.

We investigated the characteristics of the flurothyl-induced seizures and the effects of antiepileptic drugs on the flurothyl-induced seizure model in a previously untested Mongolian gerbil species. Mongolian gerbils demonstrated tonic extension immediately after or within 1 min after the appearance of clonic convulsion. Very high amplitude spike waves appeared in these regions concurrent with the appearance of clonic convulsion. When the tonic extension appeared immediately after the clonic convulsion, the high amplitude spike waves continued during tonic convulsion. When the tonic extension occurred, high amplitude spike waves appeared in these three regions within a very short time, and afterward Mongolian gerbils died. Administration of valproic acid-Na (200 mg/kg), ethosuximide (100 and 200 mg/kg), clonazepam (2 mg/kg) and diazepam (0.5, 1 and 2 mg/kg) significantly prolonged the latency of clonic convulsion. Zonisamide-Na, phenytoin and carbamazepine, however, had no such effect. In Mongolian gerbils, tonic extension was demonstrated immediately after the appearance of clonic convulsion, yet, this effect was inhibited by all these drugs in a dose-dependent manner. Diazepam completely blocked the appearance of any behavioral changes in animals. These findings suggest that diazepam has a significant effect on flurothyl-induced seizures. Flurothyl-induced convulsions are associated with GABA receptors; hence, benzodiazepine (BDP) suppression may result from the strong relation between BDP and GABAnergic neurons.

The effect of immobilization stress on the pharmacokinetics of omeprazole in rats.

The effects of immobilization stress on the pharmacokinetics of omeprazole were studied in rats. The immobilization stress for 30 or 60 min immediately after oral administration of the drug caused an increase in the time to reach the maximum concentration. However, such stress did not alter the area under the plasma concentration-time curve (AUC). When administered intravenously, the half-life during the elimination phase was significantly prolonged by 30 min of immobilization stress, but the AUC value remained unchanged. The intestinal propulsive activity was significantly decreased by immobilization stress. These findings suggest that immobilization stress reduces gastrointestinal motility. A resulting delay during the absorption phase of omeprazole occurs, although the degree of influence on overall pharmacokinetics is relatively insignificant.

Comparison of the placental transfer of halothane, enflurane, sevoflurane, and isoflurane during cesarean section.

The concentrations of placental transfer of halothane (H), enflurane (E), sevoflurane (S), and isoflurane (I) were measured in 46 patients during cesarean section. The mean inhalation times of H (0.5%), E (1%), S (0.8%), and I (0.6%) were 13 min 27 s, 13 min 49s, 13 min 20s, and 8 min 8s, respectively. The mean concentrations in the maternal artery (MA) were 5.2mg·dl-1 in H, 12.3 mg·dl-1 in E, 5.2mg·dl-1 in S, and 2.4mg·dl-1 in I. The concentration ratio between the MA and the fetal umbilical vein (UV) was 0.44 for H, 0.49 for E, and 0.38 for S, and these ratios were not significantly different for these anesthetics. Although the concentration ratio for I (0.27) was significantly lower than those of the other three anesthetics, the UV:MA ratio was calculated to be 0.4 for an inhalation time 13 min. Our result, therefore, suggests that if the inhalation times were equal, the ratios of placental transfer would not differ among these four inhalational anesthetics. The Apgar scores in these four groups were not different from that in the group given only 66% nitrous oxide in oxygen as anesthetic (N2O group). The cardiovascular changes induced by skin incision were bigger in the N2O group than in the other groups. The use of a low concentration of H, E, S, or I is, therefore, suggested to be a useful and acceptable anesthetic method for cesarean section.

Administration of MgSO4 failed to improve the neurological recovery after complete global brain ischemia in dogs.

The cerebral protective effects of MgSO4 after complete global brain ischemia were evaluated with EEG, evoked potentials (EP) and the neurological recovery score (NRS) in the dog. Complete global brain ischemia for 15 min was achieved by occluding the ascending aorta and the caval veins. The MgSO4 group (N=7) were injected with a 10% MgSO4 solution and the control group (N=7) were administered a normal saline intravenously from the beginning of the resuscitation to 48 h after ischemia. The EEG grades (1=normal, 5=flat) in the control group and the MgSO4 group were 3.9±0.1 (mean ±SEM) and 3.7±0.3, and the EEG-EP scores (6=normal, 0=serious deterioration) were 2.6±0.4 and 2.7±0.4 4h after ischemia, respectively. The 7-day survival rates for ischemia were equal in both groups (5/7:71%). The NRSs (0=death, 100=normal) in the control group and the MgSO4 group were 50±3 (n=7) and 43±9 (n=7) on the 3rd day after ischemia, and were 56±5 (n=5) and 42±12 (n=5) on the 7th day. The differences between the two groups were not significant. We conclude that MgSO4 administered after ischemia has no beneficial effects on the recovery of EEG, EP and the NRS after 15 min of complete global brain ischemia in the dog.