In their narrative review Read and Moncrieff (this issue) query the concept of depression and the efficacy and safety of two cornerstone treatments for severe illness: antidepressants and electroconvulsive therapy (ECT). Regarding their concept of depression, as ‘misery and sadness’, they ignore historical psychopathological descriptions of depression, presenting with features such as impaired cognition, psychomotor disturbance and psychosis (Kendler, Reference Kendler2016). This fundamental reframing of what depression is (and is not) colours any subsequent arguments made by the authors. Antidepressants are covered elsewhere in this issue, and we focus here on ECT, an internationally recognised evidence-based treatment for severe, sometimes life-threatening, depression (Kirov et al., Reference Kirov, Jauhar, Sienaert, Kellner and McLoughlin2021). We have already drawn attention to substantial methodological limitations in previous narrative reviews of ECT by Read and colleagues (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). These are repeated in the narrative by Read and Moncrieff and can be summarised as: selective citing and biased reporting of results. Briefly, the main arguments put forward relate to the mechanism of ECT, efficacy and side-effects.
Mechanism of ECT
As with many effective medical treatments, the precise mechanism of action of ECT is not yet fully understood (Kirov et al., Reference Kirov, Jauhar, Sienaert, Kellner and McLoughlin2021). Bizarrely, Read and Moncrieff draw on historical hypotheses predating ECT, accompanied by inflammatory language, ‘some doctors treated epilepsy by injecting the blood of ‘schizophrenics’…’. They quote doctors from the early 1940s, one of which clearly refers to brain damage from historical treatments such as insulin coma therapy rather than ECT. Additionally, it is unclear how, in stating ‘A similar line of argument was resurrected, 70 years later, by researchers who reported that ECT reduces the ‘functional connectivity’ of the brain’, the authors can imply change in Blood-Oxygen-Level-Dependent (BOLD) signal is some kind of marker for ‘brain damage’. These erroneous historical and conceptual references are accompanied by a vernacular (e.g. ‘electrocutions’) that does little to advance scientific debate or assuage concerns about impartiality.
Efficacy of ECT
Read and Moncrieff focus almost exclusively on older sham ECT (sECT) trials, going back to the 1980s. While older sECT trials have limitations, they consistently identify large reductions of depression symptoms following ECT (g = 0.85; Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). The authors suggest ECT proponents are arguing ‘RCTs aren't necessary’ and ‘non-placebo studies [are] sufficient’. Such straw-man arguments side-step the abundance of well-conducted and converging evidence from contemporary trials demonstrating the superiority of ECT over antidepressants and other brain stimulation therapies and different modes of ECT (unilateral v. bilateral) (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). These findings are important because, where possible, ‘active comparators’ rather than ‘placebo’ are the best and most ethical comparator arms.
With no evidence, the authors claim expectation effects in those previously treated with ECT would exaggerate efficacy. We compared effect sizes in those who previously received ECT v. those who had not or where previous ECT was not ascertained: the effect size was significantly smaller in those with known prior exposure (indeed almost half the size) (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). This directly opposes the expectation claim. If ECT encompasses a placebo effect, then the placebo occupies a unique place in science by working against expectation.
Another argument is the lack of benefit at follow-up in older sECT trials, which is hardly surprising. These studies did not optimally use continuation therapies, which have evidence for decreasing relapse, a feature of the underlying illness (Jelovac, Kolshus, & McLoughlin, Reference Jelovac, Kolshus and McLoughlin2013).
Safety of ECT
The authors allude to ECT causing brain damage in the discussion of its impact on memory. As above, cited evidence is historical, irrelevant, and involves backward inference. They conflate weaker neuropsychological test performance with brain damage and refer to functional rather than structural magnetic resonance imaging (MRI) changes. They selectively cite Sackeim et al. (Reference Sackeim, Prudic, Fuller, Keilp, Lavori and Olfson2007), conflating cognitive test performance with brain damage. This observational study, which included the use of outmoded sine-wave ECT, demonstrated a small mean reduction in autobiographical memory (<0.2 Z scores) at 6 months for bilateral ECT. However, this was substantially less for unilateral ECT and did not factor in the effects of depression itself on cognition or the normal rate of forgetting autobiographical memories, key areas of contemporary research. While cognitive function was poorer immediately following ECT, the authors fail to mention that Sackeim et al. (Reference Sackeim, Prudic, Fuller, Keilp, Lavori and Olfson2007) reported improved cognitive performance (including memory) on 29 of 33 assessments at 6 months, compared with pre-ECT scores. Presumably, Read & Moncrieff would not want to equate improved cognitive test performance in the longer-term with the presence of brain damage? Nor do they acknowledge ECT does not increase the risk for stroke or dementia, which might be expected if it caused ‘brain damage’ (Kirov et al., Reference Kirov, Jauhar, Sienaert, Kellner and McLoughlin2021).
Furthermore, the authors selectively cite a systematic review of subjective memory in seven questionnaire-based studies (Rose et al., Reference Rose, Fleischmann, Wykes, Leese and Bindman2003), three of which failed to meet Rose et al.'s own inclusion criteria. By contrast, Read & Moncrieff ignore a subsequent meta-analysis that demonstrated short-term reduction in cognition in the first three days after completing a course of ECT, followed by overall improvement after 15 days, with 57% of cognitive variables assessed showing positive effect sizes, ranging from 0.35 [95% CI 0.07–0.63] to 0.75 [95% CI 0.43–1.08] with the remaining variables similar to pre-ECT scores (Semkovska & McLoughlin, Reference Semkovska and McLoughlin2010).
Concerning their assertions about adverse psychological and emotional effects following ECT, Read & Moncrieff cite one small (n = 20) study that ‘targeted people who had had negative reactions to ECT…recruited by posters and flyers asking, ‘Have you been given ECT? Did you find it upsetting or distressing in any way?’ This is hardly an even-handed representation of psychological and emotional responses to ECT. They further cite Wells, Hancock, & Honey (Reference Wells, Hancock and Honey2021) as evidence of negative psychological and emotional effects, ignoring the fact that these authors clearly document both positive and negative effects in 23 individuals (largely a sample of peer supporters). In a recent qualitative study, Wells et al., also pointed out that most who had received ECT reported it as a positive experience, stating ‘ECT should be raised as a potential treatment option earlier in the treatment process. Participants suggested that this may help to reduce the stigma associated with ECT.’
Read and Moncrieff quote statistics on safety, suicide, and mortality, though again are remarkably selective. They state, ‘Numerous studies have found ECT recipients are more likely than other patients to kill themselves’. They cite one study by Munk-Olsen et al. (Reference Munk-Olsen, Laursen, Videbech, Mortensen and Rosenberg2007), which actually states ‘Although ECT patients are psychologically and physically severely ill, the decrease in mortality from natural causes implies that the treatment does not endanger but rather may have a positive effect on physical health. …The increased suicide rate among ECT patients shortly after treatment is probably a result of bias…’ Read and Moncrieff omit crucial details that the increased suicide rate is a result of bias, while a decrease in overall mortality is, as Munk-Ollsen et al. state, ‘unlikely to be a result of bias’.
Read and Moncrieff state ‘Another recent study, using the Swedish national registry, claimed its findings ‘support the continued use of ECT to reduce suicide risk in hospitalised patients who are severely depressed’ (Ronnqvist, Nilsson, & Nordenskjold, Reference Rönnqvist, Nilsson and Nordenskjöld2021). The overall difference in suicides over 12 months between the ECT group (1.1%) and non-ECT group (1.6%) was small.’ This is not an issue of ‘claimed’. The study of 28 557 showed a lower suicide rate amongst those who had received ECT compared to those who had not. The rates per group are naturally small because it is a low-incidence event; but, of the 152 who committed suicide, it equated to 28 fewer suicides in the ECT group.
Regarding mortality from physical causes, Read and Moncrieff cite Duma et al. (Reference Duma, Maleczek, Panjikaran, Herkner, Karrison and Nagele2019) who report 25.8 per 1000 experience major cardiac events. However, they neglect to mention that the same study reported all-cause mortality was low at 0.42 (0.11–1.52) deaths per 1000 patients and 0.06 (0.02–0.23) deaths per 1000 ECT treatments.
Given the problems of confounding by indication, it is worth noting the results of two large recent studies comparing safety, suicidality and mortality between people receiving and not receiving ECT, controlling for this using propensity score matching. The first, a Canadian cohort study of > 10 000 admissions, found reduced suicide rates and no clinically significant increase in medical adverse events post-ECT (Kaster et al., Reference Kaster, Vigod, Gomes, Sutradhar, Wijeysundera and Blumberger2021). The second study (a cohort of >8000 people receiving ECT) found no increase in morbidity in the ECT group (Watts, Peltzman, & Shiner, Reference Watts, Peltzman and Shiner2021).
In conclusion, Read and Moncrieff provide an inaccurate and misleading account of the evidence for ECT. Methodological mishaps include: mis-citing of studies and arguments from before ECT was even invented; a lack of identifiable data-driven hypotheses - where their hypotheses have been tested they have been shown to be incorrect (e.g. expectation effects); ignoring relevant systematic reviews and meta-analyses that oppose their argument; repeated illogical backward inferencing of brain damage from both neuropsychological test performance and functional brain imaging; and simple factual errors that pervade their narrative. As we have previously noted (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022), our collective efforts would better serve our patients by using rigorous evidence-based methods to understand and optimise ECT, one of the most effective treatments in Psychiatry.
Financial support
No financial support was received for the work.
Conflict of interest
CM and KL report no COI.
DM has received speaker's honoraria from Mecta, Otsuka and Jannsen and an honorarium from Janssen for participating in an esketamine advisory board meeting.
AHY employed by King's College London; Honorary Consultant SLaM (NHS UK)
Deputy Editor, BJPsych Open
Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, Sage, Novartis
Consultant to Johnson & Johnson
Consultant to Livanova
Received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova.
Principal Investigator in the Restore-Life VNS registry study funded by LivaNova.
Principal Investigator on ESKETINTRD3004: ‘An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression.’
Principal Investigator on ‘The Effects of Psilocybin on Cognitive Function in Healthy Participants’
Principal Investigator on ‘The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (p-TRD)’
UK Chief Investigator for Novartis MDD study MIJ821A12201
Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK)
No shareholdings in pharmaceutical companies
SJ has received honoraria for educational talks given on antipsychotics for Janssen and Sunovian. KCL has received honoraria for the educational talks he has given for Lundbeck.
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In their narrative review Read and Moncrieff (this issue) query the concept of depression and the efficacy and safety of two cornerstone treatments for severe illness: antidepressants and electroconvulsive therapy (ECT). Regarding their concept of depression, as ‘misery and sadness’, they ignore historical psychopathological descriptions of depression, presenting with features such as impaired cognition, psychomotor disturbance and psychosis (Kendler, Reference Kendler2016). This fundamental reframing of what depression is (and is not) colours any subsequent arguments made by the authors. Antidepressants are covered elsewhere in this issue, and we focus here on ECT, an internationally recognised evidence-based treatment for severe, sometimes life-threatening, depression (Kirov et al., Reference Kirov, Jauhar, Sienaert, Kellner and McLoughlin2021). We have already drawn attention to substantial methodological limitations in previous narrative reviews of ECT by Read and colleagues (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). These are repeated in the narrative by Read and Moncrieff and can be summarised as: selective citing and biased reporting of results. Briefly, the main arguments put forward relate to the mechanism of ECT, efficacy and side-effects.
Mechanism of ECT
As with many effective medical treatments, the precise mechanism of action of ECT is not yet fully understood (Kirov et al., Reference Kirov, Jauhar, Sienaert, Kellner and McLoughlin2021). Bizarrely, Read and Moncrieff draw on historical hypotheses predating ECT, accompanied by inflammatory language, ‘some doctors treated epilepsy by injecting the blood of ‘schizophrenics’…’. They quote doctors from the early 1940s, one of which clearly refers to brain damage from historical treatments such as insulin coma therapy rather than ECT. Additionally, it is unclear how, in stating ‘A similar line of argument was resurrected, 70 years later, by researchers who reported that ECT reduces the ‘functional connectivity’ of the brain’, the authors can imply change in Blood-Oxygen-Level-Dependent (BOLD) signal is some kind of marker for ‘brain damage’. These erroneous historical and conceptual references are accompanied by a vernacular (e.g. ‘electrocutions’) that does little to advance scientific debate or assuage concerns about impartiality.
Efficacy of ECT
Read and Moncrieff focus almost exclusively on older sham ECT (sECT) trials, going back to the 1980s. While older sECT trials have limitations, they consistently identify large reductions of depression symptoms following ECT (g = 0.85; Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). The authors suggest ECT proponents are arguing ‘RCTs aren't necessary’ and ‘non-placebo studies [are] sufficient’. Such straw-man arguments side-step the abundance of well-conducted and converging evidence from contemporary trials demonstrating the superiority of ECT over antidepressants and other brain stimulation therapies and different modes of ECT (unilateral v. bilateral) (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). These findings are important because, where possible, ‘active comparators’ rather than ‘placebo’ are the best and most ethical comparator arms.
With no evidence, the authors claim expectation effects in those previously treated with ECT would exaggerate efficacy. We compared effect sizes in those who previously received ECT v. those who had not or where previous ECT was not ascertained: the effect size was significantly smaller in those with known prior exposure (indeed almost half the size) (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022). This directly opposes the expectation claim. If ECT encompasses a placebo effect, then the placebo occupies a unique place in science by working against expectation.
Another argument is the lack of benefit at follow-up in older sECT trials, which is hardly surprising. These studies did not optimally use continuation therapies, which have evidence for decreasing relapse, a feature of the underlying illness (Jelovac, Kolshus, & McLoughlin, Reference Jelovac, Kolshus and McLoughlin2013).
Safety of ECT
The authors allude to ECT causing brain damage in the discussion of its impact on memory. As above, cited evidence is historical, irrelevant, and involves backward inference. They conflate weaker neuropsychological test performance with brain damage and refer to functional rather than structural magnetic resonance imaging (MRI) changes. They selectively cite Sackeim et al. (Reference Sackeim, Prudic, Fuller, Keilp, Lavori and Olfson2007), conflating cognitive test performance with brain damage. This observational study, which included the use of outmoded sine-wave ECT, demonstrated a small mean reduction in autobiographical memory (<0.2 Z scores) at 6 months for bilateral ECT. However, this was substantially less for unilateral ECT and did not factor in the effects of depression itself on cognition or the normal rate of forgetting autobiographical memories, key areas of contemporary research. While cognitive function was poorer immediately following ECT, the authors fail to mention that Sackeim et al. (Reference Sackeim, Prudic, Fuller, Keilp, Lavori and Olfson2007) reported improved cognitive performance (including memory) on 29 of 33 assessments at 6 months, compared with pre-ECT scores. Presumably, Read & Moncrieff would not want to equate improved cognitive test performance in the longer-term with the presence of brain damage? Nor do they acknowledge ECT does not increase the risk for stroke or dementia, which might be expected if it caused ‘brain damage’ (Kirov et al., Reference Kirov, Jauhar, Sienaert, Kellner and McLoughlin2021).
Furthermore, the authors selectively cite a systematic review of subjective memory in seven questionnaire-based studies (Rose et al., Reference Rose, Fleischmann, Wykes, Leese and Bindman2003), three of which failed to meet Rose et al.'s own inclusion criteria. By contrast, Read & Moncrieff ignore a subsequent meta-analysis that demonstrated short-term reduction in cognition in the first three days after completing a course of ECT, followed by overall improvement after 15 days, with 57% of cognitive variables assessed showing positive effect sizes, ranging from 0.35 [95% CI 0.07–0.63] to 0.75 [95% CI 0.43–1.08] with the remaining variables similar to pre-ECT scores (Semkovska & McLoughlin, Reference Semkovska and McLoughlin2010).
Concerning their assertions about adverse psychological and emotional effects following ECT, Read & Moncrieff cite one small (n = 20) study that ‘targeted people who had had negative reactions to ECT…recruited by posters and flyers asking, ‘Have you been given ECT? Did you find it upsetting or distressing in any way?’ This is hardly an even-handed representation of psychological and emotional responses to ECT. They further cite Wells, Hancock, & Honey (Reference Wells, Hancock and Honey2021) as evidence of negative psychological and emotional effects, ignoring the fact that these authors clearly document both positive and negative effects in 23 individuals (largely a sample of peer supporters). In a recent qualitative study, Wells et al., also pointed out that most who had received ECT reported it as a positive experience, stating ‘ECT should be raised as a potential treatment option earlier in the treatment process. Participants suggested that this may help to reduce the stigma associated with ECT.’
Read and Moncrieff quote statistics on safety, suicide, and mortality, though again are remarkably selective. They state, ‘Numerous studies have found ECT recipients are more likely than other patients to kill themselves’. They cite one study by Munk-Olsen et al. (Reference Munk-Olsen, Laursen, Videbech, Mortensen and Rosenberg2007), which actually states ‘Although ECT patients are psychologically and physically severely ill, the decrease in mortality from natural causes implies that the treatment does not endanger but rather may have a positive effect on physical health. …The increased suicide rate among ECT patients shortly after treatment is probably a result of bias…’ Read and Moncrieff omit crucial details that the increased suicide rate is a result of bias, while a decrease in overall mortality is, as Munk-Ollsen et al. state, ‘unlikely to be a result of bias’.
Read and Moncrieff state ‘Another recent study, using the Swedish national registry, claimed its findings ‘support the continued use of ECT to reduce suicide risk in hospitalised patients who are severely depressed’ (Ronnqvist, Nilsson, & Nordenskjold, Reference Rönnqvist, Nilsson and Nordenskjöld2021). The overall difference in suicides over 12 months between the ECT group (1.1%) and non-ECT group (1.6%) was small.’ This is not an issue of ‘claimed’. The study of 28 557 showed a lower suicide rate amongst those who had received ECT compared to those who had not. The rates per group are naturally small because it is a low-incidence event; but, of the 152 who committed suicide, it equated to 28 fewer suicides in the ECT group.
Regarding mortality from physical causes, Read and Moncrieff cite Duma et al. (Reference Duma, Maleczek, Panjikaran, Herkner, Karrison and Nagele2019) who report 25.8 per 1000 experience major cardiac events. However, they neglect to mention that the same study reported all-cause mortality was low at 0.42 (0.11–1.52) deaths per 1000 patients and 0.06 (0.02–0.23) deaths per 1000 ECT treatments.
Given the problems of confounding by indication, it is worth noting the results of two large recent studies comparing safety, suicidality and mortality between people receiving and not receiving ECT, controlling for this using propensity score matching. The first, a Canadian cohort study of > 10 000 admissions, found reduced suicide rates and no clinically significant increase in medical adverse events post-ECT (Kaster et al., Reference Kaster, Vigod, Gomes, Sutradhar, Wijeysundera and Blumberger2021). The second study (a cohort of >8000 people receiving ECT) found no increase in morbidity in the ECT group (Watts, Peltzman, & Shiner, Reference Watts, Peltzman and Shiner2021).
In conclusion, Read and Moncrieff provide an inaccurate and misleading account of the evidence for ECT. Methodological mishaps include: mis-citing of studies and arguments from before ECT was even invented; a lack of identifiable data-driven hypotheses - where their hypotheses have been tested they have been shown to be incorrect (e.g. expectation effects); ignoring relevant systematic reviews and meta-analyses that oppose their argument; repeated illogical backward inferencing of brain damage from both neuropsychological test performance and functional brain imaging; and simple factual errors that pervade their narrative. As we have previously noted (Meechan et al., Reference Meechan, Laws, Young, McLoughlin and Jauhar2022), our collective efforts would better serve our patients by using rigorous evidence-based methods to understand and optimise ECT, one of the most effective treatments in Psychiatry.
Financial support
No financial support was received for the work.
Conflict of interest
CM and KL report no COI.
DM has received speaker's honoraria from Mecta, Otsuka and Jannsen and an honorarium from Janssen for participating in an esketamine advisory board meeting.
AHY employed by King's College London; Honorary Consultant SLaM (NHS UK)
Deputy Editor, BJPsych Open
Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, Sage, Novartis
Consultant to Johnson & Johnson
Consultant to Livanova
Received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova.
Principal Investigator in the Restore-Life VNS registry study funded by LivaNova.
Principal Investigator on ESKETINTRD3004: ‘An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression.’
Principal Investigator on ‘The Effects of Psilocybin on Cognitive Function in Healthy Participants’
Principal Investigator on ‘The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (p-TRD)’
UK Chief Investigator for Novartis MDD study MIJ821A12201
Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK)
No shareholdings in pharmaceutical companies
SJ has received honoraria for educational talks given on antipsychotics for Janssen and Sunovian. KCL has received honoraria for the educational talks he has given for Lundbeck.