Ketamine or ECT? What Have We Learned From the KetECT and ELEKT-D Trials?

1. Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT.

Safety of and response to electroconvulsive therapy during pregnancy: Results from population-based nationwide registries.

INTRODUCTION: Psychiatric disorders are common during pregnancy, affecting up to 16% of pregnant women. Severe depression and anxiety have significant negative effects on the health of both the mother and the developing fetus. Electroconvulsive therapy (ECT) is considered a treatment option for pregnant women with severe psychiatric disorders when other treatments have been ineffective or pose risks to the fetus. Knowledge of the safety and efficacy of ECT during pregnancy, however, remains limited. METHODS: Data were obtained from nationwide registries of pregnant women in Sweden who received ECT for a severe psychiatric disorder from January 2008 to December 2021. ECT-related outcomes in pregnant women were compared by propensity score matching with a group of non-pregnant women who also received ECT. Pregnancy-related outcomes were compared with two additional control groups: one consisting of the same group of women who did not receive ECT during another pregnancy and the other composed of pregnant women admitted to inpatient psychiatric care but who did not receive ECT, matched based on propensity score. RESULTS: Ninety-five pregnant women received ECT during the study period, accounting for 97 pregnancies. The response rate to ECT in pregnant women (n = 54) was similar to the matched control group of non-pregnant women (74% vs. 65%; OR 1.61; 95% CI 0.79-3.27). Rates of adverse events related to ECT were similar to those in the control group. There were no pre-term births or severe adverse outcomes related to the pregnancy, that were close in time to ECT. Therefore, no adverse outcomes related to pregnancy and childbirth could be directly attributed to ECT. The likelihood of premature birth and a 5-min Apgar score <7 in the newborn were both significantly higher in the ECT group, compared with the matched non-ECT group (OR 2.33, 95% CI 1.15-4.73, p = 0.008, and OR 3.68, 95% CI 1.58-8.55, p < 0.001, respectively). By contrast, no significant differences were observed when women in the pregnant ECT group were compared with the same group lacking ECT during another pregnancy. CONCLUSIONS: ECT was associated with a positive treatment response in pregnant women with severe psychiatric disorders. The response rate to ECT was similar in pregnant and non-pregnant women. Nevertheless, the risks of premature birth and of a slightly poorer condition in newborns were higher in women who did than did not receive ECT, emphasizing the need for increased attention to severe psychiatric disorders during pregnancy.

Electroconvulsive therapy in children and adolescents: results from a population­based study utilising the Swedish National Quality Register.

Electroconvulsive therapy (ECT) is effective and safe for adults with severe depression, but less studied in adolescents. Here, we examined the indications, prevalence, practice, response and remission rates, and side effects in young people treated with ECT in Sweden. We also examined the usage of ECT in the transition to adult psychiatry. Using data from national patient registers and the Swedish National Quality Register for ECT (Q-ECT), we identified patients aged up to 19 years treated with ECT over a 5-year study period. Response and remission rates were analysed using the Clinical Global Impression (7-point scale)-Improvement (CGI-I) and Severity (CGI-S). A total of 118 individuals were identified, of which 105 were also enrolled in the Q-ECT. The most common indication for ECT was depression (68%; n = 80). Adolescents aged < 18 years were more severely ill before treatment than those aged 18 years (P < 0.01). Three of the hospitals in Sweden treated the majority of adolescents < 18 years old. The median number of sessions in each ECT series was seven. Unilateral placement of the electrodes was the most common (88%; n = 99). Fifty-seven percent (n = 54) of the patients responded (CGI-I, 1-2) to the treatment; remission (CGI-S, 1-2) was achieved by 32% (n = 30). Psychotic symptoms were associated with a higher response rate in patients with depression (P = 0.038). A deterioration of memory compared to pre-treatment was reported in six patients. ECT was associated with high response and remission rates in adolescents with severe psychiatric disorders after non-response to medication.

Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT).

BACKGROUND: Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression. METHODS: Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session. RESULTS: In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52). CONCLUSION: Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

Effect of electroconvulsive seizures on pattern separation.

Strategies employing different techniques to inhibit or stimulate neurogenesis have implicated a role for adult-born neurons in the therapeutic effect of antidepressant drugs, as well as a role in memory formation. Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, robustly stimulate hippocampal neurogenesis, but it is not known how this relates to either therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the ECS-derived increase in adult-born neurons would manifest in improved pattern separation ability, a memory function that is believed to be both hippocampus-dependent and coupled to neurogenesis. To test this hypothesis, we stimulated neurogenesis in adult rats by treating them with a series of ECS and compared their performances in a trial-unique delayed nonmatching-to-location task (TUNL) to a control group. TUNL performance was analyzed over a 12-week period, during which newly formed neurons differentiate and become functionally integrated in the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the delay between sample and choice, and by varying the spatial similarity between target and distracter location. Although animals learned the task and improved the number of correct responses over time, ECS did not influence spatial pattern separation ability.