Impact of different anesthetic agents (propofol, etomidate, ketamine) on seizure duration and cognitive recovery in electroconvulsive therapy

Abstract

BACKGROUND

Electroconvulsive therapy (ECT) is also an ideal treatment alternative when dealing with treatment-resistant depression, together with other severe mental conditions. Localization of seizures and cognitive effects of anesthetic agents is significantly influenced by the anesthetic used, but an optimal anesthetic method/regime remains debatable.

AIM

To identify comparative consequences of propofol, etomidate, and ketamine regarding the length of seizures and post-ECT cognition.

METHODS

The current study involved a methodical search of the literature, based on PRISMA guidelines, to identify randomized controlled trials (RCTs) and observational research studies that evaluate the difference between anesthetics used during ECT. The articles analyzed pertained to seizure durations, cognitive performance, hemodynamic factors, and recovery. The quality evaluation was done on the applicable tools of RCT and observational research. Interpretation of the statistical data, based on IBM SPSS, was conducted with the assistance of qualitative synthesis.

RESULTS

There were 24 articles taken into account, 11 RCTs and 13 observational studies identified. Several studies have revealed that etomidate is more effective in reducing seizure duration than propofol in various patient groups. Ketamine also recorded increased efficacy in antidepressant but inconsistent activity in the length of seizures. Propofol was linked with shorter recovery times, although the reduction of seizures was constant and shorter each time. The reviews revealed a significant disparity in cognitive outcomes among the agents, with etomidate exhibiting better cognitive profiles than propofol in several trials.

CONCLUSION

The available evidence in the existing literature suggests that etomidate may be beneficial in terms of seizure duration and could yield satisfactory cognitive outcomes. Ketamine shows signs of greater treatment efficacy, but its application must be carefully evaluated in regard to dosage plans. The effectiveness of seizure control can be influenced by this predictive anesthesia that accompanies the rapid recovery of activities following propofol administration. The choice of anesthetic agent should be individualized, based on the nature of the patient and the motive behind the treatment, as well as institutional policy. Large-scale RCT is needed to provide evidence-based recommendations that may be taken decisively.

Key Words: Electroconvulsive therapy; Anesthesia; Propofol; Etomidate; Ketamine; Seizure duration; Cognitive recovery

Core Tip: Etomidate most reliably preserves therapeutically adequate electroconvulsive therapy seizures and is associated with less short-term cognitive decline than propofol. Propofol shortens seizure duration, gives smoother recovery but faster emergence; ketamine adds antidepressant benefit yet has variable effects on seizure duration and raises blood pressure/heart rate. The choice of the agent depends on the primary clinical goal and the patient’s cardiovascular and cognitive risk profile.

INTRODUCTION

The response to the electroconvulsive therapy (ECT) has exceeded 70% because most of the individuals with severe mental health disorders, particularly resistant depression, are treated with it as one of the most effective measures[1,2]. Despite its demonstrated effectiveness, the procedure warrants close attention to the implementation of anesthetic protocols to achieve optimal therapeutic results and minimize undesired effects as much as possible. The choice of anesthetic agents in ECT primarily determines the seizures, events, and the condition of the treatment, and this choice can be a discriminatory factor in treatment[3,4].

ECT in use today is done in deep sedation that is provided by the use of general anesthesia and neuromuscular blockade of the patients to ensure the procedure becomes safe and comfortable. However, anticonvulsant activity can be observed when using anesthetic drugs, and this aspect can impair the effectiveness of a treatment plan[5,6]. This poses a challenging clinical situation, and this necessitates an appropriate trade-off between appropriate anesthesia and seizure maintenance. The three most popular regimens of anesthesia for ECT are propofol, etomidate, and ketamine, all of which have specific pharmacological characteristics that alter the shape of the seizure and the outcome of cognitive effects[7,8].

The use of propofol, a fast-acting and fast-clearing phenolic compound, has become a key component in the application of ECT due to its convenience in administration and patient recovery[9,10]. However, this is due to the fact that the substance possesses a potent anticonvulsant effect, causing shorter spells of seizures that negate the treatment[5,6]. Etomidate is a derivative of imidazole that has specific characteristics of ECT, as it has low anticonvulsant activity while preventing seizures[3]. It is also suitable because it has a desirable effect on hemodynamics and a minimal effect on the seizure threshold, so it is applied during ECT anesthesia[7,11]. There has also been significant interest in selective antagonists of N-methyl-D-aspartate receptors, such as ketamine, due to its synergistic effect on ECT, which has the potential to achieve superior treatment outcomes in addition to using a standard anesthesia drug[12-14].

ECT continues to be a significant issue for patients and clinicians when it comes to cognitive after-effects and memory loss, being the most important issue against the treatability of patients accepting their treatment[15-17]. Depending on the anesthetic agent employed, the cognitive outcome may be significantly affected in several ways, including actions that directly impact memory consolidation, seizure characteristics, and modes of recovery[15,16]. The information about these different effects is paramount in maximizing the risk-benefit ratio of ECT treatment.

ECT anesthesia is the subject of earlier reviews that focus on thematic entities in isolation, and there is a dearth of comparative and inter-agent effects of ECT anesthetic agents on measures of seizure control and cognitive outcome. The growing scope of randomized controlled trials (RCTs) and observational studies underscores the need to synthesize information in a systematic manner, thereby contributing to evidence-based clinical practice. This systematic review will provide an inclusive understanding of the impact of propofol, etomidate, and ketamine on ECT improvement, including the length of the seizure and cognitive restoration, to assist clinicians in making evidence-based anesthetic selections in ECT practice.

MATERIALS AND METHODS

Protocol and registration - PRISMA and PICO framework

The PRISMA was used to measure the method of the systematic review. The review methodology was determined in advance to provide methodological integrity and minimize bias during the selection of studies and data extraction. This systematic review was structured according to the PICO framework: Population (P): Adult patients (≥ 18 years) undergoing ECT for psychiatric disorders, including treatment-resistant depression and other severe mental health conditions. Intervention (I): Anesthetic agents including propofol, etomidate, ketamine, and their combinations (such as ketofol) used during ECT procedures. Comparison (C): Direct comparisons between different anesthetic agents (propofol vs etomidate vs ketamine) or combinations thereof. Outcomes (O): Primary outcomes included seizure duration and cognitive recovery measures. Secondary outcomes encompassed hemodynamic parameters, recovery times, adverse events, and treatment efficacy.

Although the primary focus of this review was on propofol, etomidate, and ketamine, studies that involved the use of thiopental or methohexital were also eligible, provided they used these agents as a comparator anesthetic during ECT. These barbiturate agents were historically used as standard reference anesthetics in the practice of ECT and were included to offer contextual comparison and to better understand the relative impacts of modern anesthetic agents on the nature of seizures and recovery.

Search strategy

A systematic literature search was conducted to identify research comparing anesthetic agents in ECT. The search activity utilized a combination of various electronic databases, which were intended to encompass RCTs as well as uncontrolled observational studies published in peer-reviewed journals. The databases were searched from inception until June 2025. The researchers were required to make at least two comparisons among the three main anesthetic drugs (propofol, etomidate, and ketamine) in relation to the ECTs and to report any results in terms of seizures after the task durations or the cognitive rehabilitation period. We used the following terms and combined them using Boolean operators (AND/OR) as appropriate: ECT, electroshock therapy, shock therapy, convulsive therapy, electroconvulsive, ECT, anesthetics, intravenous anesthetics, anesthesia, sedatives, hypnotics, propofol, ketamine, etomidate, methohexital, thiopental, and barbiturates.

Inclusion and exclusion criteria

Inclusion criteria: (1) RCTs and observational studies; (2) Adult (more than 18 years) patients undergoing ECT; (3) Comparison of propofol, etomidate, and or ketamine as anesthetic agents; (4) Reporting of the seizure duration and/or cognitive outcome; and (5) Publications in the English language.

Exclusion criteria: (1) Case reports, case series, or review articles; (2) Trial registries for the pediatric populations; (3) Investigations that did not report essential outcome measures; and (4) Phase 1, 2, and 3 trials with a lacking methodology.

Study selection and data extraction

The studies were selected independently by two reviewers to minimize the risk of bias, and data extraction was conducted accordingly. Issues of dissent were therefore discussed and a non-table agreement was reached. The study’s characteristics, including patient age and sex, anesthetic processes, seizure features, cognitive outcome, and side effects, were among the information extracted. Standardized data extraction forms were employed to induce some sense of continuity among the studies.

Quality assessment

In quality assessment, various study designs were employed, utilizing relevant tools and methods. The Cochrane tool, used to evaluate RCTs, was known as the Cochrane Risk of Bias tool (RoB 2.0). Observational experiments, on the other hand, were evaluated using the Newcastle-Ottawa Scale. Quality assessment was conducted by two different individuals, and the agreement between the two raters was calculated using Cohen’s kappa coefficient (k). A consensus on judgments was reached through the input of the third reviewer when a decision was needed.

Data synthesis

The use of a qualitative method of synthesis was chosen due to the heterogeneity of study designs, outcome measurements, anesthetic procedures, and patient groups identified in the studies. The methods of the studies, dose regimens, scales to measure cognitive aspects, and follow-up periods varied too much to allow for a quantitative meta-analysis.

Clear guidelines on narrative synthesis were followed, and the studies were categorized based on the comparison of anesthetic agents and categories of outcomes. The data were sorted and systematically extracted, organized into a comparative table, and this helped facilitate the qualitative analysis of patterns and trends. When available, descriptive statistics on the level of studies were reported; however, no pooled statistical analysis was performed, as the study itself is of a qualitative nature.

RESULTS

Study selection

A total of 24 studies were included in the initial search, comprising 11 RCTs[5-7,9,10,14,18-22] and 13 observational studies[8,11-13,15-17,23-28]. Table 1 reveals that a total of 3172 patients were treated with ECT using different combinations of anesthetics. There was a high inter-rater reliability in terms of research selection [k = 0.91, 95% confidence interval (CI): 0.85-0.97]. Selection was performed as shown in the flow diagram below (Figure 1).

Figure 1 PRISMA flow diagram of the article selection process. ECT: Electroconvulsive therapy.

Table 1 Risk of bias assessment for randomized controlled trials (n = 11).

Ref.	Random sequence generation	Allocation concealment	Blinding of participants	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias	Overall risk
Shahu et al[5], 2024	Low	Low	Low	Low	Low	Low	Low	Low
Zhong et al[14], 2016	Low	Low	Unclear	Low	Low	Low	Low	Some concerns
Erdogan Kayhan et al[22], 2012	Low	Unclear	Low	Low	Low	Low	Low	Some concerns
İkiz et al[9], 2021	Low	Low	Low	Low	Low	Low	Low	Low
Jindal et al[6], 2020	Low	Low	Low	Low	Low	Low	Low	Low
Canbek et al[7], 2015	Low	Low	Low	Low	Low	Low	Low	Low
KJ et al[21], 2025	Unclear	Unclear	Unclear	Unclear	Unclear	Unclear	Unclear	High
Mathur et al[10], 2024	Low	Low	Low	Low	Low	Low	Low	Low
Joshi et al[20], 2021	Low	Low	Low	Low	Low	Low	Low	Low
Brunelin et al[18], 2020	Low	Low	Low	Low	Low	Low	Low	Low
Guha et al[19], 2022	Low	Unclear	Low	Low	Low	Low	Low	Some concerns

Risk of bias summary statistics: Low risk of bias: 8 studies (72.7%). Some concerns: 3 studies (27.3%). High risk of bias: 1 study (9.1%).

Quality assessment results

Risk of bias assessment for RCTs: A recent overview of research studies carried out by Cochrane on the risk of bias indicated that the quality of the 11 RCTs included in it was diverse. Regarding inter-rater reliability in the risk of bias assessment, a large dominance was observed (k = 0.82; 95%CI: 0.74-0.90). The risk of bias assessment was done in detail and presented in Table 1.

Newcastle-Ottawa Scale assessment for observational studies: The evaluations of the Newcastle-Ottawa Scale in 13 observational studies showed that quality was generally available, and the inter-rater correlation was highly significant (k = 0.79, 95%CI: 0.71-0.87). The evaluation is reflected in Table 2.

Table 2 Newcastle-Ottawa Scale assessment for observational studies (n = 13).

Ref.	Selection (max 4 stars)	Comparability (max 2 stars)	Outcome (max 3 stars)	Total score	Quality rating
Bernardoff et al[15], 2026	4	2	3	9	High
Hoyer et al[12], 2014	4	2	3	9	High
Krystal et al[16], 2003	3	2	3	8	High
Kavakbasi et al[24], 2023	4	2	3	9	High
Tufek et al[13], 2014	3	1	3	7	Moderate
Kök Kendirlioğlu et al[25], 2025	3	2	3	8	High
Lundin et al[17], 2025	4	1	3	8	High
Yang et al[8], 2025	3	2	2	7	Moderate
Gurel et al[28], 2022	3	2	3	8	High
Sartorius et al[11], 2021	4	2	3	9	High
Yoon et al[27], 2023	3	2	3	8	High
Methfessel et al[26], 2023	3	2	3	8	High
Beyazyüz et al[23], 2023	3	1	3	7	Moderate

Newcastle-Ottawa Scale summary statistics: High quality (≥ 8 stars): 10 studies (76.9%). Moderate quality (6-7 stars): 3 studies (23.1%). Low quality (< 6 stars): 0 studies (0%).

Study characteristics

RCTs: The design of the RCTs incorporated was diverse, with variations in study design, patient sample, and outcome measures. The sample sizes used ranged from 40 patients to 120 patients, and most studies employed double-masked randomization procedures. Propofol, etomidate, ketamine, and their combinations are the major anesthetics to be compared (Table 3).

Table 3 Characteristics of included studies.

Ref.	Study type	n	Age (years)	Anesthetic agents	Primary outcomes	Follow-up
Shahu et al[5], 2024	RCT	60	42.3 ± 12.1	Propofol vs etomidate	Seizure duration, hemodynamics	Immediate
Zhong et al[14], 2016	RCT	90	35.2 ± 10.5	Ketamine (different doses)	Mood, neuropsychological	1 month
Erdogan Kayhan et al[22], 2012	RCT	48	44.7 ± 15.2	Ketofol vs propofol	Seizure duration, recovery	Immediate
İkiz et al[9], 2021	RCT	80	46.1 ± 13.7	Propofol vs propofol + remifentanil	Hemodynamics, seizure duration	Immediate
Jindal et al[6], 2020	RCT	60	38.9 ± 11.3	Etomidate vs propofol	Motor seizure duration	Immediate
Canbek et al[7], 2015	RCT	120	41.6 ± 14.8	Propofol vs etomidate vs thiopental	Seizure parameters, recovery	Immediate
Mathur et al[10], 2024	RCT	100	43.2 ± 12.9	Propofol vs ketofol	Seizure duration, hemodynamics	Immediate
Joshi et al[20], 2021	RCT	80	40.5 ± 13.2	Ketofol vs etomidate	Seizure duration, recovery	Immediate
Brunelin et al[18], 2020	RCT	58	47.8 ± 15.1	Propofol + ketamine vs propofol	Clinical response	6 weeks
Guha et al[19], 2022	RCT	50	39.7 ± 12.6	Propofol vs ketamine	Efficacy, cognitive function	2 weeks
Bernardoff et al[15], 2026	Observational	156	52.3 ± 16.4	Various	Cognitive function	6 months
Hoyer et al[12], 2014	Observational	1253	54.7 ± 17.2	Ketamine, etomidate, thiopental, propofol	Seizure parameters	Immediate
Krystal et al[16], 2003	Observational	89	48.2 ± 14.3	Ketamine vs methohexital	Seizure duration, cognitive	1 week
Kavakbasi et al[24], 2023	Observational	124	45.9 ± 13.8	Thiopental vs propofol	Cognitive effects, seizure	1 month
Tufek et al[13], 2014	Observational	210	47.3 ± 15.6	Various	Seizure duration, recovery	Immediate
Kök Kendirlioğlu et al[25], 2025	Observational	78	44.1 ± 12.7	Ketamine + ECT	Treatment resistance	3 months
Lundin et al[17], 2025	Observational	892	49.6 ± 16.8	Various	Treatment outcomes	17 years
Yang et al[8], 2025	Observational	186	41.2 ± 14.5	Various	Cognitive function	6 months
Gurel et al[28], 2022	Observational	120	43.8 ± 13.9	Ketofol, etomidate, propofol, thiopental	Seizure parameters	Immediate
Sartorius et al[11], 2021	Observational	234	52.1 ± 17.3	S-ketamine + propofol	Seizure quality	Immediate
Yoon et al[27], 2023	Observational	98	46.7 ± 14.2	Etomidate vs propofol	Clinical response	3 months
Methfessel et al[26], 2023	Observational	67	51.4 ± 16.1	Propofol/esketamine vs methohexital	Seizure quality	Immediate
Beyazyüz et al[23], 2023	Observational	84	42.9 ± 13.4	Propofol vs ketamine-propofol	ECT parameters	Immediate

RCT: Randomized controlled trial; ECT: Electroconvulsive therapy.

The large effects on the duration of seizure of etomidate and propofol, as reported by Shahu et al[5] in 2024, are evident. According to the comparison made, the authors reported a significant difference in the paired median differences in favor of etomidate, with a difference of 12.4 seconds (P < 0.001). Good hemodynamic results were also observed in the case of etomidate compared to propofol. ECT treatment has a positive effect on mood outcomes and neuropsychological functioning in patients, with the greatest impact observed at a moderate dose of ketamine exposure (Zhong et al[14], 2016) (Table 3).

Erdogan Kayhan et al[22] in 2012 explored the use of ketofol (a ketamine-propofol formulation) and found an improvement in seizure quality and a safe recovery profile with a tolerable recovery profile compared to propofol monotherapies. Notably, ketofol stood out in the study, being found to provide better maintenance of seizure duration compared to propofol monotherapy (P < 0.05) (Table 3).

In a study by İkiz et al[9] in 2021, propofol and a combination of propofol with remifentanil were compared. The authors extrapolated that the propofol-remifentanil combination achieved a stable hemodynamic state, and the addition of remifentanil had minimal impact on seizure duration. However, through the combination therapy, it took a longer time to recover (Table 3).

In particular, using the same comparisons, Jindal et al[6] in 2020 evaluated motor seizure upon comparing etomidate and propofol and demonstrated that the latter is more effective in inducing a sufficient seizure (etomidate: 28.4 ± 6.2 seconds vs propofol: 20.1 ± 4.8 seconds, P < 0.001) (Table 3).

Observational studies: The observational studies provided a fair representation of real-life evidence on the performance of the anesthetic agent. In them, more patients were usually examined and in greater numbers, and their follow-up was longer compared to that conducted during RCTs (Table 3).

Hoyer et al[12] in 2014 took a broader, more comprehensive look at the general retrospective analysis using a population of 1253 ECT sessions and two comparisons: Ketamine vs etomidate and ketamine vs thiopental/propofol. The study has established that etomidate and ketamine are associated with a longer duration of seizures compared to propofol. Additionally, etomidate has been found to be the most consistent in terms of effectiveness across diverse patient populations (Table 3).

They were also compared with ketamine as compared to anesthesia with methohexital in a research done by Krystal et al[16] in 2003, where they determined that ketamine caused partial seizures that could last a long time and perhaps enhance the aspect of cognitive recovery as compared to other anesthetics that are commonly used. It has also been suggested in the paper that the quality of the seizure on an electroencephalography is better in subjects who were given ketamine (Table 3).

Bernardoff et al[15] in 2026 specifically discussed the effects of anesthesia on the extent of cognitive functionality and concluded that the application of different anesthetic agents resulted in the emergence of varying levels of cognitive dysfunction. In the proposed research, it was proposed that the mental effect of etomidate would be able to reduce more than the propofol among the patients who were suffering depressive disorders that would not be treated effectively through various methods (Table 3).

Seizure duration outcomes

The duration of the seizure is a major outcome variable used in most studies and has shown a tendency towards similar results in selective anesthetic agent actions. There are significant variations in various studies on the anesthetic agents as identified by the qualitative synthesis. Table 4 presents the findings of individual studies to illustrate the patterns identified in various research.

Table 4 Seizure duration outcomes by anesthetic agent.

Ref.	Propofol (seconds)	Etomidate (seconds)	Ketamine (seconds)	Ketofol (seconds)	P value
Shahu et al[5], 2024	20.4 ± 4.6	32.8 ± 6.2	-	-	< 0.001
Erdogan Kayhan et al[22], 2012	22.1 ± 5.3	-	-	28.7 ± 6.4	< 0.05
Jindal et al[6], 2020	20.1 ± 4.8	28.4 ± 6.2	-	-	< 0.001
Canbek et al[7], 2015	23.2 ± 5.7	29.6 ± 7.1	-	-	< 0.001
Mathur et al[10], 2024	21.5 ± 4.9	-	-	26.8 ± 5.7	< 0.01
Joshi et al[20], 2021	-	31.2 ± 7.8	-	29.3 ± 6.9	0.082
Hoyer et al[12], 2014	22.8 ± 6.2	30.1 ± 8.4	25.6 ± 7.1	-	< 0.001
Krystal et al[16], 2003	-	-	28.3 ± 6.7	-	-
Gurel et al[28], 2022	19.7 ± 4.2	28.9 ± 6.8	-	27.4 ± 5.9	< 0.001

Cognitive recovery outcomes

Divergence was also high as various assessment tools and methods were used to determine cognitive outcomes in different studies. There were complicated patterns in the qualitative synthesis of the results of cognitive performance data linked to the effects of anesthetic agents in ECT. Table 5 presents the individual study results related to the cognitive examination.

Table 5 Cognitive outcomes by anesthetic agent.

Ref.	Cognitive assessment tool	Propofol	Etomidate	Ketamine	P value
Zhong et al[14], 2016	MMSE, TMT-A, TMT-B	-	-	Dose-dependent improvement	< 0.05
Bernardoff et al[15], 2026	MoCA, RBANS	Moderate impairment	Mild impairment	-	< 0.05
Krystal et al[16], 2003	MMSE, orientation	-	-	Less impairment	< 0.01
Kavakbasi et al[24], 2023	MMSE, clock drawing	Moderate impairment	Mild impairment	-	< 0.05
Yang et al[8], 2025	MoCA, RBANS	Variable	-	-	NS
Guha et al[19], 2022	MMSE	Moderate impairment	-	Mild impairment	< 0.05

Individual study recovery times: Propofol: Consistently shorter recovery times across studies (range: 6.2-10.4 minutes). Etomidate: Moderate recovery times (range: 10.1-14.7 minutes). Ketamine: Longer recovery times (range: 13.2-18.2 minutes). Ketofol: Intermediate recovery times (range: 8.1-12.3 minutes). MMSE: Mini-Mental State Examination; TMT-A: Trail Making Test - Part A; MoCA: Montreal Cognitive Assessment; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; NS: Not significant.

Hemodynamic parameters

Studies have shown that there was a significant variation in the hemodynamic responses among the anesthetic agents. Hemodynamic data qualitative analysis revealed similar patterns of agent-specific effects across all investigations. Hemodynamic findings in the individual study are given in Table 6.

Table 6 Hemodynamic outcomes by anesthetic agent.

Ref.	Parameter	Propofol	Etomidate	Ketamine	P value
Shahu et al[5], 2024	MAP change (mmHg)	+18.2 ± 8.4	+12.3 ± 6.7	-	< 0.01
Shahu et al[5], 2024	HR change (bpm)	+22.1 ± 9.3	+16.4 ± 7.2	-	< 0.05
İkiz et al[9], 2021	MAP change (mmHg)	+16.7 ± 7.9	-	-	-
İkiz et al[9], 2021	HR change (bpm)	+19.8 ± 8.6	-	-	-
Mathur et al[10], 2024	MAP change (mmHg)	+17.3 ± 8.1	-	-	-
Zhong et al[14], 2016	MAP change (mmHg)	-	-	+24.6 ± 10.2	-
Zhong et al[14], 2016	HR change (bpm)	-	-	+28.3 ± 11.7	-

MAP: Mean arterial pressure; HR: Heart rate.

When comparing etomidate to propofol in terms of hemodynamics, there were reduced fluctuations in blood pressure and heart rate. There was also a sympathomimetic risk of ketamine, including an increase in blood pressure and heart rate that can be challenging to patients who have cardiovascular disease.

Adverse events and safety profile

The safety profiles of the anesthetic agents varied significantly in a set of studies. Through negative occurrence analysis, differences in protection characteristics of agents in various investigations were identified. Table 7 presents the results of combining the tables from individual studies that report their patterns of adverse events.

Table 7 Adverse event patterns from individual studies.

Adverse event	Propofol studies	Etomidate studies	Ketamine studies	Ketofol studies
Nausea/vomiting	Lower rates reported across studies	Higher rates consistently reported	Variable rates across studies	Intermediate rates reported
Myoclonus	Minimal occurrence reported	Frequently reported across studies	Low occurrence reported	Low to moderate occurrence
Emergence phenomena	Rare occurrence	Occasional reports	Frequently reported concern	Occasional reports
Prolonged recovery	Minimal reports	Moderate occurrence	Consistent reports across studies	Variable reports
Hypotension	Occasional reports	Rare occurrence	Minimal reports	Occasional reports
Hypertension	Rare occurrence	Rare occurrence	Frequently reported	Moderate occurrence

DISCUSSION

The qualitative analysis of this systematic review sheds significant light on how different anesthetics can influence changes in the duration of seizure and cognition restoration after ECT. The similarity of the findings from many studies suggests that etomidate has a longer seizure duration than propofol, and it should be considered in cases where seizure adequacy is the primary concern[5-7]. This observation aligns with the pharmacodynamics of etomidate, which exhibits very low anticonvulsant effects compared to the strong gamma-aminobutyric acid-mediated anticonvulsant effects of propofol[3].

An explanation has been provided to support all the reports, suggesting that the clinical experience regarding the duration of seizures and the effectiveness of ECT is debatable. Other studies have suggested that the quality of seizures may prove to be a better indicator than the duration of seizure[4]. However, the fact that a longer duration of seizures could result in more favorable treatment outcomes in the majority of studies demonstrates the clinical importance of this parameter[12,27]. Such findings, as stated by Hoyer et al[12] and Jindal et al[6], are persuasive since etomidate does not increase seizure duration, which has significant clinical implications.

The role of ketamine in ECT anesthesia is an area of clinical practice that is coming into its own, and the emerging data provide the hope of a synergistic antidepressant activity beyond the guise of anesthetic considerations[1]. The study by Zhong et al[14] and Krystal et al[16] suggests the possibility of a unique positive effect of ketamine due to its neuroplasticity level-altering mechanism, which involves blocking an N-methyl-D-aspartate receptor or a combination of the two. Nevertheless, there is still a need to research the ketamine schedule and the patients who will be selected to undergo ECT[11,25].

The cognitive sequelae of using different anesthetic agents are an important aspect of ECT application, as cognitive side effects remain the primary factor limiting the favorability of treatment[2]. The research conducted by Bernardoff et al[15] and Kavakbasi et al[24] suggests that etomidate may offer cognitive advantages over propofol; however, the mechanism underlying this difference is not well understood. A reduction in seizure features with etomidate may lead to the implementation of a more effective treatment plan, and it may decrease the total volume of ECTs, thereby minimizing cumulative exposure to cognitive impairment.

The hemodynamic demands of different anesthetic drugs relate to questions of patient safety and treatment viability[3]. The hemodynamic profile of etomidate is particularly attractive in patients with comorbid conditions that affect the cardiovascular system. Conversely, there are groups among the patients who are hypersensitive to ketamine due to sympathetic effects, which can cause an issue. The findings of the articles by Shahu et al[5] and Canbek et al[7] demonstrate that such hemodynamic differences can be clinically relevant, and the decision of anesthetizing choice must rely on them.

A novel set of combination anesthetic medications, i.e., ketofol, has been proposed as a means to establish a trade-off between conflicting objectives of maintenance of seizures and recovery profile[4]. Ketofol may offer an advantage compared to single-drug practice, as mentioned in studies by Erdogan Kayhan et al[22] and Mathur et al[10]. However, further investigations are still needed to determine the optimal dose ratio and the category of patients[23,28].

Variability in the research, the population of patients, and outcomes measurement were both a limitation and a strength in this systematic review. On one hand, such diversity can encompass all clinical circumstances; on the other hand, it makes it impossible to perform a meta-analysis with adequate statistical power and draw a conclusion regarding the most effective anesthetic practices. The incomparability of different studies is also due to the use of varying assessment instruments for the cognitive assessment method and seizure assessment method, resulting in a lack of consistency in assessment methods.

From a practical clinical perspective, the choice of an anesthetic agent in ECT should be individualized, depending on the patient’s treatment priorities and individual characteristics. Etomidate appears to be appropriate under the condition that the primary objective is to provide the highest adequacy of seizures, particularly in patients with or having high seizure thresholds or those with suboptimal seizure quality. Propofol is a viable alternative when there is a high priority, rapid emergence, hemodynamic control, and short-term recovery, although it has the drawback of reduced seizure threshold. Ketamine may be considered as an option in treatment-resistant depression patients in which the adjunctive antidepressant effects are sought, but the sympathomimetic profile and slower recovery are known. Ketofol is a more balanced choice, offering desirable seizure control and more predictable recovery, which may prove useful in situations where conflicting clinical goals need to be fulfilled simultaneously.

It is inevitable that the understanding of these results is hindered by the following significant limitations. Firstly, the majority of studies have been conducted in single centers, involving relatively small samples; thus, the field is limited in its capability to be applied to diverse clinical populations. Second, the studies included in the review did not have identical outcome measures, making it impossible to directly compare them, and a bias in the study synthesis may occur. Third, the majority of studies are short-term, and due to the small sample size, long-term cognitive outcomes and the effectiveness of long-lasting treatments cannot be determined.

The clinical implications of these findings are that, in ECT, anesthetics should be personalized according to patient considerations, treatment goals, and institutional policies. Etomidate may be preferred even though disadvantages in the recovery profile may occur in patient populations where maximum seizure adequacy is the paramount consideration. Propofol can be acceptable in patients where a quick recovery is of added importance to some extent, provided that it comes at the cost of extending the duration of seizure. One treatment, ketamine, would be considered by patients who have had depression because they tend to react effectively to its antidepressant effects.

The additional research should be conducted in a large, multi-center, randomized controlled study that employs standardized outcomes and is based on a broader duration of follow-up. Validated cognitive measurement instruments in ECT practice enable the comparison of results across more studies. In addition, a study examining a specific anesthetic regimen tailored to the patient's background and reaction to treatment may provide a means of rationalizing the risk-benefit of ECT treatment.

The economic consequences of different anesthetic agents should also be a concern in clinical decision-making. Although cost-effectiveness was not specifically discussed in this systematic review, a potential economic benefit of a conservative reduction in treatment time, provided by a more effective anesthetic regimen, could be realized in terms of reduced costs and overall healthcare systems.

Several significant limitations must be noted when interpreting these qualitative data. There were considerable levels of heterogeneity regarding the research methods, the subjects studied, the anesthetic dose schedule, and the outcome measurement research instruments, which prevented the merging of quantitative studies and weakened the power of the synthesized results. The differences in the cognitive assessment tools, methods used to measure seizures, and duration of follow-up in the studies used were inhibitors to making a direct comparison and raised the possibility of bias in the synthesis.

The majority of the included studies were single-center studies with a relatively small overall sample size, which may not be applicable to diverse populations. The long-term cognition and durability of treatment could not be understood due to the majority of short-term follow-up studies. Additionally, there was variability in the reporting of confounding factors, including electrode position, stimulation parameters, and the medication used simultaneously, which could have contributed to the results.

The interpretation of cognitive outcomes is limited by heterogeneity due to the wide variety of assessment tools used across studies, which evaluate non-identical cognitive domains. In addition, the timing of cognitive assessment varied substantially, with most studies reporting short-term or intermediate post-ECT effects, while long-term cognitive outcomes were less consistently evaluated. These factors should be considered when comparing anesthetic agents and extrapolating the durability of observed cognitive changes. Reported cognitive outcomes primarily reflect short- to intermediate-term post-ECT effects, as long-term cognitive follow-up was inconsistently assessed across studies and evaluated using heterogeneous instruments.

CONCLUSION

The systematic review provides exhaustive information on the comparative effects of propofol, etomidate, and ketamine on the duration of the discrete seizure and cognitive rebound in the course of ECT. It has become irrefutable that etomidate can offer a superior profile of seizure duration compared to propofol, while maintaining a satisfactory profile of cognitive and hemodynamic status. The potential of the higher therapeutic effect employed during the use of ketamine, as the special property of the pharmacological agent, is yet to be idealized.

The result of the practice involves personalizing the available anesthetic options based on patient-specific qualities and treatment-specific bundles. Etomidate appears to be most appropriate in the scenario where the skill of seizure is necessary, as well as propofol in the situation where quick awakening is mandatory, and ketamine in the scenario where one should utilize additional antidepressant characteristics of the drug. The use of combination drugs (in this case ketofol) has the potential for optimization of the balance between the preservation of the seizures and the recovery characteristics.

These methodological implications of the review highlight the need for standardization of outcome measures and subsequent follow-up studies with long-term investigations to create a definitive picture of the comparative effects associated with different anesthetic agents. Evidence-based criteria development for anesthetic selection in ECT is also a field where large, multi-site, RCTs with standardizable procedural steps, measures, and assessments of outcome variables may prove useful.

The current literature is based on evidence, and it supports the administration of etomidate as an initial anesthetic agent in settings where the duration of the seizure is of utmost concern, and propofol in instances where a quick recovery is needed. An alternative that must be considered in the case of patients with treatment-resistant depression who are capable of responding is ketamine. Still, the last approval of individualizing the anesthetic agent follows the factors concerning the patient, the rules of the institutes, and the experience of the clinicians in the given categories.

In certain aspects, this synthesis of the evidence has identified some of the missing spots in terms of what constitutes the best anesthetic measures when outside of ECT. The greater comparative research of a significant nature, which is orderly within the set parameters of the outcomes, is to be focused on in future research, including long-term follow-ups and a more comprehensive follow-up. Various per-patient anesthesia strategies, tailored to the specific characteristics of each patient and their unique response to therapy, are one direction of further ECT optimization.

In the extension of evidence regarding ECT, this systematic review enhances the evidence base for informed decisions regarding the selection of anesthetics. Through this review, the available evidence, in the form of RCTs or observational studies, is provided to enable clinicians to draw informed conclusions on what can be done to optimize the anesthesia process in ECT. The study reiterates the importance of considering both seizure- and cognitive-related features in the choice of anesthetics, as well as the necessity of individualized care.

Its application in clinical practice is not limited to clinical anesthesia alone and can be applied to broader aspects of ECT optimization, including patient preparation, monitoring schedules, and aftercare. Since the evidence related to the choice of anesthetic used during ECT is provided in the current review, it is possible to note that it is one of the crucial points of ECT optimization that is likely to play a key role in altering the efficacy and tolerability rates of ECT.