Narp Mediates Antidepressant-Like Effects of Electroconvulsive Seizures.

Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy. Based on multiple measures, we infer that Narp knockout mice undergo normal seizure activity in this paradigm, yet fail to display antidepressant-like behavioral effects of ECS. Although Narp deletion does not suppress ECS-induced proliferation in the dentate gyrus, it blocks dendritic outgrowth of immature granule cell neurons in the dentate molecular layer induced by ECS. Taken together, these findings indicate that Narp contributes to the antidepressant action of ECT and implicate the ability of ECS to induce dendritic arborization of differentiating granule cells as a relevant step in eliciting this response.

Electroconvulsive therapy pre-treatment with low dose propofol: comparison with unmodified treatment.

BACKGROUND: Whilst electroconvulsive therapy (ECT) is routinely administered under anesthesia in developed nations, in many developing countries, ECT is still administered unmodified. This practice has attracted considerable scrutiny with calls to ban unmodified ECT. However, there are no affordable alternatives for many poor, acutely ill psychiatric patients. We evaluated whether administration of intravenous propofol 0.5 mg/kg for sedation by the ECT psychiatrist just prior to otherwise unmodified treatment improved acceptance of and reduced anxiety surrounding the treatment. METHOD: We conducted an open label trial at The King George's Medical University in Lucknow, India. Forty-nine patients received propofol pre-treatment and 50 patients received unmodified treatment as usual. RESULTS: Socio-demographic profiles, diagnoses and clinical responses were comparable. Patients who received propofol experienced less anxiety monitored by the State-Trait Anxiety Inventory just prior to ECT (p < 0.001), and had a more favorable attitude towards treatment assessed by an established questionnaire (Freeman and Kendell, 1980). Propofol patients were less likely to experience post-ictal delirium monitored by the CAM-ICU (p = 0.015) and had fewer cognitive side-effects on the MMSE (p = 0.004). There were no adverse events associated with propofol administration. CONCLUSION: Whilst unmodified ECT should never be used when modified ECT under anesthesia is available, we have found low dose propofol can be safely administered by the ECT psychiatrist to sedate patients pre-treatment who would otherwise receive completely unmodified treatment. The intervention was associated with reduced anxiety and a more positive attitude towards ECT, without compromising efficacy. A randomized double blind controlled study is necessary to confirm these benefits.

ECT treatment outcomes following performance improvement changes.

Differences in electroconvulsive therapy (ECT) outcomes were explored following changes in ECT administration at our institution. Two changes were introduced: (a) switching the anesthetic agent from propofol to methohexital, and (b) using a more aggressive ECT charge dosing regimen for right unilateral (RUL) electrode placement. Length of stay (LOS) and number of treatments administered per patient were monitored. A retrospective analysis was performed of two inpatient groups treated on our Mood Disorders Unit: those who underwent ECT in the 12 months prior to the changes (n = 40) and those who underwent treatment in the 12 months after the changes (n = 38). Compared with patients receiving ECT with RUL placement prior to the changes, patients who received RUL ECT after the changes had a significantly shorter inpatient LOS (27.4 versus 18 days, p = 0.028). Treatment efficacy monitored by the Montgomery Asberg Depression Rating Scale was not impacted. The change in anesthetic agent and charge dosing each accounted for 11% of the variance in LOS among patients receiving RUL ECT. The implemented changes in ECT administration positively impacted outcome for patients receiving treatment with RUL electrode placement.

Flumazenil pretreatment in benzodiazepine-free patients: a novel method for managing declining ECT seizure quality.

OBJECTIVE: Seizure threshold increases with successive electroconvulsive therapy (ECT) treatments, which can be especially problematic when treating older patients who have higher seizure thresholds at baseline because ECT devices are limited by the amount of charge that can be delivered. CASE REPORTS: We present a case series of 3 older patients who had long ECT courses that were complicated by inability to generate seizures, poor quality seizures, and inadequate clinical response despite established measures to lower seizure threshold including prehydration, hyperventilation, and minimizing methohexital dose using remifentanil. As preclinical studies show electroconvulsive seizure increases diazepam binding, we hypothesized that a contributor to declining seizure quality and inadequate ECT responsiveness in these individuals was enhanced benzodiazepine receptor function, although none of the 3 patients were taking benzodiazepines or any other anticonvulsant medication. Accordingly, we pretreated patients with flumazenil, a competitive inhibitor at the benzodiazepine-binding site, and observed improvement in seizure quality and clinical response. CONCLUSION: Flumazenil pretreatment of elderly ECT patients with declining seizure quality and inadequate clinical response in the setting of repeated treatments may represent a novel strategy for managing such patients. A clinical trial would be required to test this hypothesis.

Decreasing adverse outcomes of unmodified electroconvulsive therapy: suggestions and possibilities.

Electroconvulsive therapy (ECT) is far and away the most effective treatment for depression and quite effective for a range of other psychiatric conditions that are unresponsive to medication. Electroconvulsive therapy in the developed world has been administered with anesthesia, muscle relaxants, and ventilation since the mid-1950s following 20 years of unmodified treatment. However, in much of the developing world, ECT continues to be administered unmodified because of lack of resources. We review the efficacy of unmodified compared with modified treatment. We also review the potential drawbacks of unmodified treatment including fear and anxiety, worse postictal confusion, fracture risk, and the negative effects of unmodified treatment on how ECT is perceived in the general community. Finally, we consider potential solutions in developing countries to minimize adverse outcomes of unmodified treatment by pretreating patients either with low-dose benzodiazepines or sedating, but not anesthetizing, dosages of anesthetic agents. Randomized controlled trials are necessary before either of these options could be considered an acceptable alternative to completely unmodified treatment when modified treatment is unavailable.

Safety considerations for outpatient electroconvulsive therapy.

As electroconvulsive therapy (ECT) requires general anesthesia and is associated with both cognitive and non-cognitive side effects, careful consideration must be given to the safety aspects of providing ECT on an outpatient basis. Drawing upon published literature and their clinical experience administering outpatient ECT, the authors propose best practices for safely providing ECT to outpatients. They review criteria for selecting patients for outpatient ECT as well as treatment and programmatic issues. The authors highlight the importance of educating referring clinicians as well as patients and their families about factors involved in the safe delivery of ECT for outpatients. Fiscal considerations and the drive toward reduced length of stay are prompting insurers and caregivers to choose outpatient over inpatient ECT. For each patient, such a choice merits a careful analysis of the risks of outpatient ECT, as well as the implementation of measures to ensure patient safety.

A within-subject comparison of propofol and methohexital anesthesia for electroconvulsive therapy.

OBJECTIVES: The optimal anesthetic for electroconvulsive therapy (ECT) is a frequently studied but unresolved issue. Methohexital and propofol are 2 widely used anesthetic agents for ECT. The purpose of this study was to determine which of the 2 agents was associated with superior clinical outcomes. METHODS: Records from all patients who had undergone separate ECT courses with methohexital and propofol between 1992 and 2008 (n = 48) were reviewed for a retrospective within-subject comparison of outcome measures. The clinical outcomes we examined were number of treatments required in a course of ECT, changes in the Montgomery-Åsberg Depression Rating Scale and Mini Mental Status Examination, and length of stay in the hospital after initiation of ECT. Additionally, we compared treatment delivery between methohexital and propofol treatment courses, measuring rate of restimulation for brief seizures, seizure duration, percentage of treatments that were bilateral, and average charge administered. RESULTS: Data from 1314 treatments over 155 ECT courses were reviewed. Improvement in depressive symptoms, based on the Montgomery-Åsberg Depression Rating Scale, was not affected by choice of anesthetic agent. However, when right unilateral electrode placement was used, patients receiving propofol required significantly more treatments than those receiving methohexital. Propofol was also associated with a significantly higher requirement for bilateral ECT and higher stimulus dosing. Seizure duration was significantly shorter in the propofol condition, with more patients requiring restimulation for brief seizures. Length of stay in the hospital and cognitive outcomes were not significantly different between propofol and methohexital treatments. CONCLUSIONS: We recommend methohexital as the induction agent of choice for ECT, especially with right unilateral placement.