Different regimens of intravenous sedatives or hypnotics for electroconvulsive therapy (ECT) in adult patients with depression

Depression is a common mental disorder. It can present as loss of interest or pleasure, sadness, disturbed sleep or appetite, feelings of guilt or low self worth. In 2008, the World Health Organization (WHO) estimated that depression was the second leading cause of disability-adjusted life-years among all men and women between 15 and 44 years of age. The treatment of choice for severe and recurrent depression is electroconvulsive therapy (ECT). ECT involves the application of an electrical current to the patient's head. The aim is to induce a controlled convulsion. Patients usually undergo several sessions of ECT.

To minimize adverse events and improve the quality of ECT, patients receive anaesthetic agents such as intravenous sedatives or hypnotics. These agents can influence the effectiveness of ECT but can cause potential adverse effects. It would be helpful to identify which is the best anaesthetic agent for ECT in this group of patients.

This Cochrane review examined whether different types of anaesthetic agents could have an effect on anti-depression therapy and reported on the safety of those agents. The evidence is current to December 2012. We included in this review 18 randomized controlled trials (599 participants). We analysed nine pairs of comparisons: methohexital versus propofol; thiopental versus propofol; etomidate versus propofol; thiopental versus etomidate; etomidate versus methohexital; methohexital versus midazolam; thiopental versus midazolam; midazolam versus propofol; and thiamylal versus propofol.

Our analysis revealed no difference in the reduction of depression scores when methohexital was compared with propofol. Propofol reduced seizure duration to a greater extent than methohexital. No difference in seizure duration was noted when thiopental was compared with propofol. Patients recovered faster from anaesthesia when propofol rather than thiopental was used. Adverse events related to anaesthesia induction agents and to the treatment for depression were not well reported in most trials. We found the quality of the evidence to be low. Larger well-designed randomized controlled trials are needed. More clinically relevant outcomes (such as remission of depressive symptoms and postanaesthetic adverse events) during a longer follow-up period should be reported in future studies.

We reran the search in Feburary 2017. Four potential new studies of interest were added to a list of ‘Studies awaiting Classification' and will be incorporated into the formal review findings during the review update.

Authors' conclusions: 

Most of the included studies were at high risk of bias, and the quality of evidence was generally low. The studies were not designed to detect clinically relevant differences in depression scores. Anaesthetic agents should be chosen on the basis of adverse effect profile, emergence and how these medications affect seizure duration. If it is difficult to elicit an adequately long seizure, methohexital may be superior to propofol (low-quality evidence). If a patient is slow to recover from anaesthesia, propofol may allow a faster time to follow commands than thiopental (low-quality evidence). A factor of clinical concern that was not addressed by any study was adrenal suppression from etomidate. Optimal dosages of intravenous sedatives or hypnotics have not yet been determined.

Larger well-designed randomized studies are needed to determine which intravenous anaesthetic medication leads to the greatest improvement in depression scores with minimal adverse effects.

Read the full abstract...

Depression is a common mental disorder. It affects millions of people worldwide and is considered by the World Health Organization (WHO) to be one of the leading causes of disability. Electroconvulsive therapy (ECT) is a well-established treatment for severe depression. Intravenous anaesthetic medication is used to minimize subjective unpleasantness and adverse side effects of the induced tonic-clonic seizure. The influence of different anaesthetic medications on the successful reduction of depressive symptoms and adverse effects is unclear.


This review evaluated the effects of different regimens of intravenous sedatives and hypnotics on anti-depression efficacy, recovery and seizure duration in depressed adults undergoing ECT.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from 1966 to 31 December 2012). We handsearched related journals and applied no language restrictions. We reran the search in Feburary 2017. Four potential new studies of interest were added to a list of ‘Studies awaiting Classification' and will be incorporated into the formal review findings during the review update.

Selection criteria: 

We included randomized controlled trials (RCTs) and cross-over trials evaluating the effects of different intravenous sedatives and hypnotics for ECT. We excluded studies and trials using placebo or inhalational anaesthetics and studies that used no anaesthetic.

Data collection and analysis: 

Two review authors independently assessed trial quality and extracted data. When possible, data were pooled and risk ratios (RRs) and mean differences (MDs), each with 95% confidence intervals (CIs), were computed using the Cochrane Review Manager statistical package (RevMan).

Main results: 

We included in the review 18 RCTs (599 participants; published between 1994 and 2012). Most of the included trials were at high risk of bias.

We analysed the results of studies comparing six different intravenous anaesthetics.

Only a few studies comparing propofol with methohexital (four studies) and with thiopental (three studies) could be pooled.

No difference was noted in the reduction of depression scores observed in participants treated with propofol compared with methohexital (low-quality evidence). These four studies were not designed to detect differences in depression scores.

The duration of electroencephalograph (EEG) and of motor seizures was shorter in the propofol group compared with the methohexital group (low-quality evidence). No difference was seen in EEG seizure duration when propofol was compared with thiopental (low-quality evidence).

Time to recovery (following commands) was longer among participants after anaesthesia with thiopental compared with propofol (low-quality evidence).

For the remaining comparisons of anaesthetics, only single studies or insufficient data were available. Adverse events were inadequately reported in eligible trials, and none of the included trials reported anaesthesia-related mortality.