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REVIEW

CURRENT
OPINION Electroconvulsive therapy (ECT) in schizophrenia:
a review of recent literature
Sohag N. Sanghani a, Georgios Petrides a, and Charles H. Kellner b

Purpose of review
ECT remains an important, yet underutilized, treatment for schizophrenia. Recent research shows that
medication-resistant patients with schizophrenia, including those resistant to clozapine, respond well to ECT
augmentation. The purpose of this article is to review recent studies of the use of ECT in the treatment of
schizophrenia.
Recent findings
We performed an electronic database search for articles on ECT and schizophrenia, published in 2017.
The main themes of these articles are: epidemiological data on ECT use from various countries;
retrospective studies, prospective studies and meta-analyses focusing on efficacy and cognitive side-effects
of ECT in schizophrenia; ECT technical parameters and potential biomarkers.
Summary
There is growing evidence to support the use of ECT for augmentation of antipsychotic response in the
treatment of schizophrenia. Cognitive side-effects are generally mild and transient. In fact, many studies show
improvement in cognition, possibly related to the improvement in symptoms. There is wide variation among
countries in the use of ECT for the treatment of schizophrenia. There are also variations in the choice of ECT
electrode placement, parameters and schedules. These technical differences are likely minor and should not
interfere with the treatment being offered to patients. Further, long-term studies are needed to optimize ECT
treatment parameters, to examine the effect of maintenance ECT and to investigate neuroimaging/biomarkers
to understand the mechanism of action and identify potential response predictors to ECT.
Keywords
electroconvulsive therapy, schizophrenia

INTRODUCTION and Adams [3], in a Cochrane review, have suggested

Electroconvulsive therapy in schizophrenia
The notion that epilepsy and schizophrenia are
incompatible diseases led to the development of
convulsive therapy by Meduna in 1934 [1]. The first
patients treated by Meduna, and by the originators of
electroconvulsive therapy (ECT), Cerletti and Bini
[2], in 1936, were patients diagnosed with schizo-
phrenia. When chlorpromazine was introduced into
clinical practice in 1952, ECT was the most popular
treatment for acute psychosis. With the introduction
of antipsychotic medications, the use of ECT for
schizophrenia declined in the United States, the
UK and parts of Europe, and depression remained
the main indication for ECT. However, in many parts
of the world, including Asian countries, ECT contin-
ued to be a common treatment for schizophrenia. In
the last decade, there has been renewed interest in
this use of ECT in western countries and especially for
the treatment of medication-resistant cases. Tharyan
that ECT, combined with antipsychotic medication,
may be considered an option for patients with schizo-
phrenia, to target rapid global improvement and
symptom resolution in the context of limited
response to medication alone. The American Psychi-
atric Association’s taskforce on ECT previously
reviewed the literature on the combination of ECT
a
Department of Psychiatry, Donald and Barbara Zucker School of
Medicine at Hofstra/Northwell, Electroconvulsive Therapy (ECT) Divi-
sion, The Zucker Hillside Hospital, Northwell Health, Glen Oaks and
b
Electroconvulsive Therapy (ECT) Service, New York Community Hospi-
tal, Brooklyn, New York, USA
Correspondence to Sohag N. Sanghani, MD, MPH, Assistant Professor,
Department of Psychiatry, Donald and Barbara Zucker School of Medi-
cine at Hofstra/Northwell, Director, Electroconvulsive Therapy (ECT)
service, The Zucker Hillside Hospital, 75–59 263rd Street, Glen Oaks,
NY 11004, USA. Tel: +1 718 470 5720;
e-mail: ssanghani@northwell.edu
Curr Opin Psychiatry 2018, 32:000–000
DOI:10.1097/YCO.0000000000000418

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YCO 310315
Schizophrenia and related disorders
KEY POINTS
 There is wide variation across countries in the use of
ECT for treating schizophrenia.
 Emerging evidence shows that ECT augmentation of
antipsychotic medication is highly effective in the
treatment of schizophrenia, including medication-
resistant schizophrenia.
 Clozapine is a particularly effective antipsychotic
medication to combine with ECT
 The cognitive effects of ECT are mostly mild and
transient.
 The absolute differences between various ECT electrode
placements and stimulus parameters appear to be
minor, but further studies are needed.
and antipsychotic medication for treatment of med-
ication-resistant schizophrenia. The taskforce con-
cluded that a substantial number of patients with
medication-resistant schizophrenia benefit when-
ever treated with the combination of ECT and anti-
psychotic medications [4].
Many studies and reports have appeared in the
last few years examining the role of ECT in the
treatment of schizophrenia. The study by Petrides
et al. [5] has revived interest in ECT augmentation of
antipsychotic medications in general, and cloza-
pine, in particular. In this trial, 50% of the ECT
group met the a priori response criterion of 40%
reduction in the positive symptom subscale of the
Brief Psychiatric Rating Scale (BPRS) [6] vs. 0 (0%) in
the non-ECT group. Nonresponders from the non-
ECT group received ECT in the cross-over phase, and
47.4% met the response criterion. This study shows
that the clozapine–ECT combination has a syner-
gistic effect and is more effective than clozapine
alone in medication-resistant schizophrenia [5].
In this manuscript, we review studies related to
the use of ECT in schizophrenia published in 2017.
METHODS
We performed an electronic database search for
articles on ECT and schizophrenia, published in
2017, summarized the main findings of relevant
articles, and divided them into the main themes
that emerged.
Electroconvulsive therapy use for
schizophrenia in different countries
There were six reports on the use of ECT for schizo-
phrenia in different countries. There is wide
2 www.co-psychiatry.com
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variation in ECT practices in these countries, which
reflects not only variations in access to services and
patients’ acceptance of the treatment but also clini-
cians’ experience in using ECT for schizophrenia, as
well as their perception of the existing literature on
this topic.
&
Knight et al. [7 ] reported on predictors of ECT
use in all adult psychiatric inpatient services in the
state of Ontario, Canada. Of the 153 023 assess-
ments, 7323 (4.8%) revealed a history of ECT use.
Among the patients with schizophrenia, only 1834
(3.1%) patients received ECT, accounting for about
one-fourth of the patients receiving ECT.
&
Asztalos et al. [8 ] performed a survey of psychi-
atric units in Hungary and reported that Hungary
has seen a decline in the overall use of ECT between
2002 and 2014. The number of patients treated with
ECT decreased by about half. Among the patients
who received ECT, 31.6% were diagnosed with
schizophrenia in 2014, compared with 55.6% in
2002. In contrast, the use of ECT for schizophrenia
has increased in China. In a cross-sectional study of
patients with schizophrenia, 4.7% out of 2696
patients received ECT in 2006 and 7.7% out of
2466 schizophrenia patients received ECT in 2012
&
[9 ]. In another similar study with smaller sample
sizes (n ¼ 409 and 514, respectively), comparing ECT
use among schizophrenia patients in 2009 in China
and Japan, 15.2% of the patients in China and 1.8%
&
of the patients in Japan received ECT [10 ].
In a study from the Danish patient registry, the
authors reported that between 2008 and 2014, 7% of
the patients receiving ECT had a diagnosis of schizo-
phrenia and another 2.7% had a diagnosis of schiz-
&
oaffective disorder [11 ].
&
Gazdag et al. [12 ] reviewed the literature on ECT
practices in the Central–Eastern European countries
and reported that out of the 11 countries for which
data were reported, schizophrenia was the main
indication for ECT in five of them. More specifically,
these countries and the respective year of data
were: Hungary (2002), Czech-Republic (2010–
2011), Estonia (2010), Lithuania (2010) and Croatia
&
(2012–2013) [12 ].
Electroconvulsive therapy augmentation of
antipsychotic medications: efficacy and
cognitive side-effects
Nine studies reported on the efficacy and tolerability
of the strategy of augmenting antipsychotic medi-
cations with ECT. In doing so, researchers have
adopted different approaches. While reviewing this
literature, it must be remembered that in medica-
tion trials in schizophrenia, ‘response’ is defined as
20% improvement in symptoms. Notwithstanding
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the limitations in the design, in many of the ECT
trials reviewed here, a large group of patients (70–
85%) receiving ECT met the 20% response criterion
and a substantial number met 30 or 40% improve-
ment criteria. These findings need to be interpreted
in light of various strengths and limitations of the
individual study designs: sample size, definition of
the patient population, level of medication refrac-
toriness, clozapine refractoriness, open label or
blinded, prospective or retrospective, randomized
or not, fixed number or response-based treatment
schedule, variations in the ECT parameters [i.e.
bitemporal, bifrontal or right unilateral (RUL), selec-
tion of the pulse width], and quality of assessment
of cognition.
Despite the heterogeneity of the study designs
and various degrees of chronicity and medication
resistance, it is worth noting that none of these
studies report negative results and all of them report
various degrees of improvement. Table 1 provides a
summary of retrospective and prospective studies of
this treatment approach. More details of the indi-
vidual studies are provided in the following text.
Retrospective studies
&&
Lin et al. [13 ], published 1-year outcomes in schizo-
phrenia patients using data from Taiwan’s National
Health Insurance Program, which had enrolled
99.8% of the population by 2009. Two thousand
and seventy-four patients with illness duration of
1 year or more, who received their first ECT between
2002 and 2011, were compared with a matched
group of patients who received antipsychotic med-
ications only. In an elegant mirror-image design, in
which each patient served as his/her own control,
they compared outcomes 1 year before and after the
index hospitalization. For the ECT group, the rate of
psychiatric hospitalization posttreatment was sig-
nificantly lower than the rate during the year before
treatment [53.4 vs. 59.4%, odds ratio (OR) ¼ 0.74,
95% confidence interval (CI) [0.65–0.85] and there
was no significant change in the direct medical
costs. However, there was a significant increase in
direct medical costs as well as a non-significant
increase in the rate of psychiatric hospitalizations
in the non-ECT group. An important aspect of the
study is that the authors excluded patients receiving
maintenance ECT, perhaps weakening the overall
calculated efficacy of ECT.
&&
Kaster et al. [14 ] published a retrospective
report of 144 patients with schizophrenia or schiz-
oaffective disorder who received at least one acute
course of ECT (total ¼ 171 ECT courses) from 2009 to
2014 at an academic center in Toronto, Canada.
Approximately 91% of the patients received
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Electroconvulsive therapy in schizophrenia Sanghani et al.
bilateral ECT. On the basis of the Clinical note-based
Clinical Global Impression (c-CGI) data of 168 treat-
ment courses, 76.7% of them resulted in patient
response. On the basis of the Clinical Global Impres-
sion-Improvement (CGI-I) data in 89 treatment
courses, 82% resulted in patient response. Clinically
significant cognitive impairment was observed in
only 9% of treatment courses (n ¼ 8) and severe
cognitive impairment was not observed in any
course. Whenever comparing the use of antiepilep-
tic drugs, this was significantly higher in the ECT
courses of nonresponders (17.9%) compared with
responders (3.9%; P ¼ 0.007). Previous good
response to ECT was significantly more common
among responders (36.4% of courses) than nonres-
ponders (15.4% of courses; P ¼ 0.017). Among those
with a referral indication of failed pharmacother-
apy, 72% met response criteria.
&&
Grover et al. [16 ] published a retrospective
study of 59 patients with treatment-resistant schizo-
phrenia/schizoaffective disorder, who had received
the combination of clozapine and ECT in India. Of
the 53 patients with the Positive and Negative Syn-
drome Scale (PANSS) ratings, 32 (60%) had more
than a 30% and 43 (81%) had more than a 20%
reduction in the PANSS scores. Five patients with
catatonia had more than a 50% reduction in symp-
toms based on the BFCS. Eight (13.6%) of the
patients reported mild cognitive impairment and
2 (3%) experienced delirium after an ECT treatment.
Long-term follow-up data was available for 47
patients for an average of 29.7 months (range: 1–
120 months). A majority of these patients (72%)
continued taking clozapine and remained relatively
well. Additional ECT treatments were required for
only three patients.
&
Kim et al. [19 ] published a retrospective study of
ECT augmentation on seven strictly defined cloza-
pine-resistant schizophrenia patients in the Repub-
lic of Korea from December 2012 to April 2015.
There was a significant (26%) decrease in the PANSS
score (P ¼ 0.0284). Most (71%) were identified as
having a 20% or more reduction in the PANSS score.
None of the patients showed any persistent adverse
cognitive effects, as assessed by the MMSE-KC (Mini-
Mental State Examination, Korean Version of the
Consortium).
&&
Tor et al. [21 ] published a retrospective, natu-
ralistic study comparing different forms of ECT in a
tertiary psychiatric hospital in Singapore that treats
approximately 80% of the nation’s patients with
schizophrenia. They included 62 patients who
received ECT during the period between 2014 and
2016 with any of the following four modalities:
bitemporal ECT, 0.5 ms pulse-width with age-based
dosing, RUL ECT, 0.5 ms pulse-width with seizure
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 4
Table 1. Retrospective and prospective of electroconvulsive therapy in schizophrenia published in 2017
Control Average number Efficacy outcome Cognitive outcome
Studies Study design Patients n group ECT parameters of ECT treatments measure measure Finding

Retrospective studies
Lin Mirror-image, 1 year SCZ (inpatients, 2074 2074 Not available 7.3  5.9 Rate of Psychiatric None Significant decrease in the rate of
et al. pre and post-ECT duration of Inpatients on matched Hospitalization psychiatric hospitalization post ECT.
&&
[13 ] period evaluation illness ECT þ APs Inpatients Direct Medical Costs Significant increase in the direct medical
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> 1 year) on APs only, ED visits costs in the non-ECT group.

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Significantly greater decrease in ED visits in
the ECT group.
Significant increase in the days of
Schizophrenia and related disorders

psychiatric hospitalizations and days of

overall hospitalizations in the non-ECT
group.
Kaster Chart Review SCZ or SAD 144 patients (171 None 91% of patients received 12.2  6.5 (1–38) CGI - I [15] 4-point clinician- rated 76.7% of ECT courses resulted in patient
et al. courses of ECT) 1.5 X ST Bilateral ECT, c - CGI transient cognitive response per c - CGI
&&
[14 ] 1 ms pw impairment scale 82.0% of ECT courses resulted in patient
response per CGI - I
9.0% of ECT courses had clinically
significant cognitive impairment.
No case of severe cognitive impairment
Grover Chart review Treatment 59 patients on None Bilateral, Brief pulse, 13.95 PANSS [17] Patient self-report 60% patients had >30% reduction in the
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et al. resistant ECT þ CLZ Constant energy (SD:7.67) (Range: BFCS [18] PANSS score.
&&
[16 ] SCZ/SAD 5–45) (3 subjects 81% had > 20% reduction in the PANSS
received score
maintenance ECT) 5 patients with catatonia had 50%
reduction in BFCS
85% of the clozapine-refractory patient
group (n ¼ 13) had >20% reduction in
PANSS score.
13.6% had mild cognitive impairment and
3% had delirium
Kim Chart Review Clozapine 7 patients on None Bilateral, Brief pulse 13.4 PANSS MMSE-KC [20] Significant reduction in the PANSS score
et al. resistant ECT þ CLZ (SD: 4.5) Mean reduction: 25.5%(14.3)
&
[19 ] SCZ 71.4% patients had  20% reduction
No persistent adverse cognitive effects
Tor et al. Naturalistic SCZ 62 patients on None 1) bitemporal, 0.5 ms pw, 9.8 BPRS[6] Total Score MoCA (Singaporean Significant improvement in the BPRS score
&&
[21 ] comparison of ECT þ APs age-based dosing (age (SD: 3.4) Psychotic Symptoms version)[22] in local and Psychotic Subscale in the entire
4 different ECT in years - 10%) subscale of BPRS languages group and across the 4 treatment groups
modalities (n ¼ 25) MoCA delayed recall No significant differences between the 4
2) RUL, 0.5 ms pw, ST subset (anterograde treatment groups
based dosing (n ¼ 15) memory) 64.5% of patients showed 40% reduction of
3) bitemporal, 0.5 ms pw, the BPRS psychotic subscale score.
ST based dosing Significant improvement in MoCA scores
(n ¼ 11) from baseline. No significant difference
4) bifrontal, 1.0 ms pw, between the 4 ECT types.
ST based dosing Group 1 with significant impairment in
(n ¼ 11) anterograde memory compared to
baseline

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 Table 1 (Continued)
Control Average number Efficacy outcome Cognitive outcome
Studies Study design Patients n group ECT parameters of ECT treatments measure measure Finding

Prospective studies
Bansod Randomized, Outpatients with 82 patients on None bitemporal, 1.5 ms pw Fixed course of 8 PANSS WMS [24] Significant and clinically meaningful
et al. nonblind, SCZ, acutely ECTþAPs (n ¼ 31) ECTs Autobiographical improvement in the PANSS positive,
&&
[23 ] naturalistic ill, but not bifrontal, 1.5 ms pw (First 4 treatments- Memory negative and total score.
necessarily (n ¼ 27) alternate days, 5th Interview [25] Improvement on the PANSS positive scale
treatment- RUL, 1.5 ms pw (n ¼ 24) after 3 days, significantly less with RUL compared with
refractory 6th after 4 days and bifrontal or bitemporal.
last 2 at weekly No significant difference across the 3
interval) groups in PANSS negative, general
psychopathology and total scale scores.
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Significant post-ECT impairment on WMS

performance on all subtests for the whole
sample.
No significant difference across the groups
on WMS for personal/current
information and orientation subtests.
For all the remaining subtests, impairment
was significantly greater with bitemporal
compared with RUL and bifrontal. No
significant differences between RUL and
bifrontal groups.
On Autobiographical memory, a small but
significantly greater degree of forgetting
with bitemporal as compared with RUL or
bifrontal.
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Vuksan Cusa Open label, Treatment- 31 patients on None bitemporal ECT, 1 ms pw, 10.2 (7–14) PANSS MMSE[27] Significant improvement in clinical
et al. prospective study resistant SCZ ECT þ APs Initial dose: age in CGI[15] Battery of symptoms and CGI scores.
&

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[26 ] years - 10% Neuropsychological 85% of the patients had 20% reduction in
tests the PANSS score. 33% with  40%
reduction in the PANSS score
Significant improvement in short and long-
term verbal memory and executive
function/cognitive flexibility.
Kumar Longitudinal follow up SCZ 49 patients on None bitemporal, 1.5 ms pw, 7.92 (SD: 2.5) Data not HMSE[30] ECT-induced acute cognitive impairment
et al. study of cognition ECT þ APs 1.5 x ST reported Color Trails test -1 normalized by the end of 3 months post-
&
[28 ] in participants of bifrontal, 1.5 ms pw, 1.5 and 2[31] ECT
RCT comparing x ST COWA No significant difference in various
bifrontal and [32] cognitive measures between the 2
bitemporal ECT placements at 3 months.
[29]
Dalkiran Open label study Treatment 31 patients on None bitemporal ECT (short- Data not reported PANSS Emotion Recognition Significant improvement in the total PANSS
et al. resistant ECT þ APs pulse, biphasic current) Test constructed scores, negative and general subscales.
&
[33 ] SCZ from Ekman and Improvement in the positive subscale
Friesen’s ‘Pictures approaching significance (P ¼ 0.062).
of Facial Affect’ No worsening in facial emotion recognition
[34] ability
Significant increase in rates of recognition of
disgusted facial expression.
Significant improvement in response time to
fear and happy facial expression.

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APs, Antipsychotics; BFCS, Bush Francis Catatonia Rating Scale; c - CGI, Clinical note Clinical Global Impression (4 point scale); CGI-I, Clinical Global Impression-Improvement Scale; COWA, Controlled Oral Word
Association; ECT, Electroconvulsive therapy; ED, Emergency Department; HMSE, Hindi Mental Status Examination; MMSE-KC, Mini-Mental State Examination, Korean Version of the Consortium; MoCA, Montreal Cognitive
Assessment; ms, millisecond; PANSS, Positive and Negative Syndrome Scale; pw, pulse width; RUL, Right Unilateral; SAD, Schizoaffective disorder; SCZ, Schizophrenia; ST, Seizure threshold; WMS, Wechsler Memory scale.
Electroconvulsive therapy in schizophrenia Sanghani et al.

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Schizophrenia and related disorders
threshold-based dosing, bitemporal ECT, 0.5 ms
pulse-width with seizure threshold-based dosing
and, bifrontal ECT, 1 ms pulse-width with seizure
threshold-based dosing. There was a significant
improvement in the BPRS score and psychotic sub-
scale scores for all four types of ECT. A total of 64.5%
of patients showed a 40% reduction of the BPRS
psychotic subscale score. Response rates did not
differ significantly among the four types of ECT.
In the overall group, there was a nonsignificant
trend towards improvement on the paranoid sub-
scale. The improvement was significant in both
the bitemporal ECT groups as well as RUL ECT
group but did not reach significance in the
bifrontal ECT group. There was a significant
improvement in the MoCA score; from baseline
(mean- ¼ 16.94) to post-ECT score (mean ¼ 20.91)
without any significant difference between the
four modalities.
Prospective studies
&&
Bansod et al. [23 ] conducted a randomized, non-
blind, naturalistic comparison of efficacy and cog-
nitive outcomes using RUL, bifrontal and
bitemporal electrode placement in 24, 27 and 31
outpatients with schizophrenia, respectively, in
India. After eight ECTs, there was a significant
and clinically meaningful improvement in the over-
all sample for the PANSS positive, negative, general
psychopathology and total scores. There was no
significant difference across the three treatment
groups. The absolute difference between groups
on all the cognitive measures was small. While
the authors recommend a preference for bifrontal
ECT, they also support the use of moderately supra-
threshold RUL ECT, with the option of switching to
bifrontal or bitemporal ECT in the event of inade-
quate response. Limitations of this study include:
lack of formal determination of seizure threshold,
pulse width of 1.5 ms, which is wider than the 0.5–
1.0 ms commonly used, fixed length treatment
schedule, nonblinded raters and patients, small
but significant differences in cognition scores at
baseline between the groups favoring RUL on most
of the items and outpatient status, indicating a
relatively higher functioning group that was not
necessarily treatment refractory.
&
Vuksan Cusa et al. [26 ] conducted an open-label
prospective study of ECT augmentation of antipsy-
chotic medication in 31 patients with treatment-
resistant schizophrenia in Croatia. After ECT,
patients had significant improvement in their CGI
scores. Eighty-five percent of the patients had a 20%
reduction in the PANSS score and 33% of the
patients exhibited at least a 40% reduction in the
6 www.co-psychiatry.com
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PANSS scores. Several cognitive measures showed
improvement post-ECT.
&
Kumar et al. [28 ] conducted a longitudinal
follow-up study of cognition in patients with
schizophrenia who had received bifrontal and
bitemporal ECT in a previously reported study of
six acute treatments by Phutane et al. [29] that had
demonstrated superiority of bifrontal ECT in both
clinical and cognitive outcomes. Forty-nine of the
original 63 patients, had follow-up evaluations. The
authors found that ECT-induced cognitive impair-
ments had normalized by 3 months post-ECT and
there was no significant difference in various cog-
nitive measures between bifrontal and bitemporal
ECT.
&
Dalkiran et al. [33 ] published an open-label
study of ECT augmentation of antipsychotic medi-
cations in 31 patients with treatment-resistant
schizophrenia in Turkey. They reported significant
improvement in the total PANSS scores, as well as in
the negative and general subscales (P < 0.001 for
each scale). The Emotion Recognition Test, admin-
istered before and after the ECT course, showed a
significant increase in the rate of recognizing the
disgusted facial expression as well as significant
improvement in the response time to the fear and
happy facial expressions.
Meta-analyses
There were three meta-analyses that looked at ECT
&
augmentation of antipsychotic medications [35 –
&
37 ].
&
Gu et al. [36 ] performed a meta-analysis of
randomized controlled trials (RCTs) in China and
included four studies comparing ECT alone to anti-
psychotic medications alone, and three studies com-
paring ECT with antipsychotic medications to
antipsychotic medications alone. The results sug-
gested that ECT alone and ECT with antipsychotic
medications, were superior to antipsychotic medi-
cations alone as measured by the PANSS total score;
however, there was no significant difference in
improvement in the agitation sub-score. Of note,
all included studies were rated as of ‘low’ or ‘very
low’ quality, with inconsistent methodologies.
Ahmed et al. [35 ], reviewed 23 studies (n ¼ 1179
&
patients) in a systematic review, and meta-analyzed
13 studies to examine the effects of clozapine with
ECT and nonclozapine antipsychotic medication
with ECT. They included six studies with clozapine
with ECT and seven with nonclozapine antipsy-
chotic medication with ECT. The efficacy of both
these combinations was significantly better than the
antipsychotic medications alone. The overall effect
size was 0.89 (95% CI 0.68–1.09) for nonclozapine
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 Table 2. Studies on biomarkers in relation to schizophrenia and electroconvulsive therapy published in 2017
Study ECT Group Comparison ECT Mean number
Studies Approach Characteristics group Healthy control parameters of ECT sessions Finding

Senyurt Serum total SCZ (n ¼ 11), Bipolar None Healthy controls Not reported Not reported After the last ECT, TOS values in patients with major depression
&
et al. [46 ] oxidant status disorder (n ¼ 8) (n ¼ 37), age and SCZ were significantly lower than the before ECT values
(TOS), serum and Major and gender OSI values decreased significantly after the last ECT in SCZ
total depression (n ¼ 14) matched patients. No statistically significant decrease in other
antioxidant diagnoses.
status (TAS) Nonsignificant increase in TAS values after the last ECT, in all
and oxidative the three diagnoses.
stress index The findings suggest that ECT may not lead to oxidative stress
(OSI) but on the contrary, may reduce oxidative stress in SCZ
patients.
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Barhale Change in serum Paranoid SCZ None None Bilateral, Brief 6.1 (SD: 0.2) No significant change in serum oxytocin concentration in the
&
et al. [47 ] Oxytocin (n ¼ 13), pulse ECT, 3 20 patients with schizophrenia and other nonaffective
concentration Disorganized SCZ times/week psychoses after the first ECT.
after the first (n ¼ 1), There was a significant decrease in psychosis severity.
ECT nonaffective No significant correlation between the oxytocin response to the
psychosis (n ¼ 6), first ECT and the improvement in the BPRS ratings across the
mania (n ¼ 10) and ECT course.
major depression
(n ¼ 3)
Thomann MRI-Voxel based Medication resistant Medication Healthy control RUL, Brief pulse, SCZ: 11.3  1.7 SCZ: 4 patients with clinical response (50% improvement), and
&
et al. [48 ] morphometry SCZ patients resistant MDD (n ¼ 21) 2.5 x ST MDD: 10.8  2.5 5 with partial improvement (25% improvement) on PANSS
and RSFC receiving ECT þ patients score.
medications (n ¼ 9) receiving ECT RUL ECT was associated with an ipsilateral increase in GMV
þ Medications within the medial temporal lobe including the superficial
(n ¼ 12) nucleus of the amygdala, the anterior part of the
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hippocampus and insula.

In SCZ patients: Significant increase in GMV was seen in

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Amygdala and Insula.
RSFC changes were not diagnosis-specific and consisted of
reduction in RSFC between right amygdala and the right TP,
the MPFC, the right and left posterior insula and the right
DLPFC. RSFC increased along the ventral amygdalofugal
pathway, specifically towards the hypothalamus.
&
Li et al. [49 ] Multivariate SCZ patients SCZ patients Healthy controls Bilateral ECT, 5 7–10 ECTs Significant improvement in the PANSS total scores in both
pattern receiving ECT þ receiving (n ¼ 34) times in week groups.
recognition antipsychotics antipsychotics 1, three times No significant difference in cognitive performance between
methods using (n ¼ 13) only (n ¼ 16) in second groups.
structural and week, twice in After ECT, classification scores of the patients were decreased.
resting state third week and Patients with lower baseline classification scores responded
fMRI taper off better to ECT. No significant relationship seen in the
antipsychotics only group.
Classification scores of resting state fMRI may be an important
predictor of treatment outcome.
Huang Resting state SCZ patients SCZ patients Healthy control bitemporal ECT, 11.5  1.1 In comparison to antipsychotics alone, ECT þ antipsychotic
&
et al. [50 ] fMRI, gFCD receiving ECT þ receiving (n ¼ 23) pw ¼ 1.0 ms, group showed increase in gFCD within the left Pcu, vMPFC
antipsychotics antipsychotics 3 times/week and dMPFC i.e. key areas of Default Mode Network (DMN).
(n ¼ 21) only (n ¼ 21)

APs, Antipsychotics; BT, Bitemporal; DLPFC, dorsolateral prefrontal cortex; dMPFC, dorsal medial prefrontal cortex; ECT, Electroconvulsive therapy; fMRI, functional Magnetic Resonance Imaging; gFCD, global functional
connectivity density; GMV, Grey Matter Volume; IL-4, Interleukin -4; MDD, Major Depressive Disorder; MPFC, medial prefrontal cortex; MPO, Myeloperoxidase; MRI, Magnetic Resonance Imaging, ms, millisecond; NF-

www.co-psychiatry.com
kB, nuclear factor- kB; Pcu, Precuneus; RSFC, Resting State Functional Connectivity; RUL, Right Unilateral; SCZ, Schizophrenia; ST, Seizure threshold; TGF-b, Transforming growth factor - b; TP, Temporo-parietal junction;
vMPFC, ventral medial prefrontal cortex.
Electroconvulsive therapy in schizophrenia Sanghani et al.

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CE: Alpana; YCO/310315; Total nos of Pages: 10;
YCO 310315
Schizophrenia and related disorders
with ECT and 1.50 (95% CI 1.06–1.94) for clozapine
with ECT.
&
Zheng et al. [37 ] published a meta-analysis of 11
RCTs of ECT–antipsychotic medication combina-
tion compared with antipsychotic medication
monotherapy published in Chinese, with regards
to memory impairment on various scales. The
ECT–antipsychotic medication combination was
associated with greater impairment on the memory
quotient of the Wechsler Memory Scale – Revised,
Chinese version (WMS-RC) [38] immediately after
the ECT course but not at 1 and 2 weeks post-ECT.
The analysis of each category included five or fewer
trials, with significant heterogeneity between them,
with only two of the trials being classified as ‘high
quality.’
Electroconvulsive therapy augmentation of
antipsychotics: treatment parameters
Various technical treatment parameters are believed
to influence the clinical outcome of ECT. These
include electrode placement, pulse width, the
amount of stimulus charge and the frequency
of treatments.
Historically, bitemporal placement with brief-
pulse (pulse width: 0.5–1.5 ms) stimulus has been
the most widely used technique for the treatment of
schizophrenia and is the most commonly used tech-
nique in the studies reviewed earlier in this article.
&
In the article by Kumar et al. [28 ] reviewed above, at
3 months follow-up, there were no significant differ-
ences between the bifrontal and bitemporal place-
ments in terms of cognitive effects. The articles by
&& &&
Bansod et al. [23 ] and Tor et al. [21 ] also
attempted to address this issue. Theoretically,
although bifrontal ECT may be expected to show
a superior efficacy-cum-neurocognitive effect pro-
file, the absolute differences between the techniques
are very small and probably clinically insignificant.
&
Kellner et al. [39 ] reviewed the existing litera-
ture on left unilateral electrode placement (LUL).
The studies reviewed show that the seizures induced
by LUL ECT are similar in efficacy to those of
bitemporal and RUL placement. LUL can be
an effective treatment of both depression and
schizophrenia, especially in patients with cranial
defects or metallic implants that preclude the other
placements.
&
Youssef and Sidhom [40 ] reported the first
human preliminary data of a course of Low-Ampli-
tude Seizure Therapy (LAP-ST). LAP-ST was devel-
oped hypothesizing that low-amplitude current
would result in a more focal stimulus and minimal
spread of the electrical field to deeper structures like
hippocampus and temporal lobes, regions believed
8 www.co-psychiatry.com
Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
to be responsible for the memory side effects of ECT
[41,42]. They enrolled 22 patients in an open label
trial of LAP-ST with RUL placement at suprathres-
hold dose (6 ST). For the patients with schizophre-
nia or SAD (n ¼ 11), there was a significant
improvement in psychotic symptoms as rated by
the BPRS. For the entire sample, there was no signif-
icant change in MMSE. The mean number of LAP-ST
sessions was 5.7 (SD 3). The median time to full
orientation was 4.5 min [interquartile range
(IQR) ¼ 3.2–10, n ¼ 20), considerably faster than
reported for RUL ECT trials [43–45]. These prelimi-
nary results are encouraging and the field may see
more trials with this approach in the future.
Electroconvulsive therapy augmentation of
antipsychotic medications: biological
markers (neuroimaging, serum markers)
There is increased interest in understanding the
mechanism of action of ECT in the treatment of
schizophrenia as well as identifying appropriate
predictors of response. Table 2 summarizes neuro-
imaging studies and studies of various serum bio-
markers. Although no firm conclusions can be
drawn from these studies with small sample sizes
and methodological limitations, these early find-
ings could lead to future studies.
CONCLUSION
Recent findings from multiple studies from different
countries, as well as meta-analyses of previous stud-
ies, strengthen the existing evidence demonstrating
a strong augmentation effect of ECT to antipsy-
chotic medication treatment for schizophrenia.
The studies by Lin et al. [13 ] (n ¼ 2074) and by
&&
Grover et al. [16 ] (n ¼ 47) also report that improve-
&&
ment from an acute course of ECT is associated with
sustained long-term benefits. Whether the improve-
ment is the direct long-term treatment effect of
ECT or an indirect effect because of improved medi-
cation compliance, or both, needs to be further
examined with studies of maintenance ECT in
schizophrenia. Although most of the studies
reviewed here have described the effect of ECT on
the positive symptom subscale of the PANSS or the
psychotic symptom subscale of the BPRS, most of
them have not described the specific effect of ECT
on delusions and hallucinations separately. Future
studies should separately report the data on the
effect of ECT on the core positive symptoms of
schizophrenia, that is, delusions, hallucinations
and disorganization.
The literature from 2017 reviewed here shows
that cognitive side-effects of ECT are mostly mild
Volume 32  Number 00  Month 2018
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YCO 310315
and transient. Several studies actually showed
improvement in cognition. It is possible that the
improvement in symptoms may have contributed
to the improvement in attention and concentration
and cooperation, interpreted as improvement in
cognition. There is wide variation across countries
in the choice of ECT as a treatment option for
schizophrenia. There is also a wide range of varia-
tion across treatment settings in the choice of ECT
parameters, electrode placement and treatment
schedules. Brief pulse, bilateral ECT has been the
most widely used and studied technique for the
treatment of schizophrenia. The absolute differen-
ces between various electrode placements and
parameters appear to be minor. This indicates that
treatment parameters can be individualized to meet
individual patient needs, but further research with
larger studies is needed.
Large-scale studies of adequate sample size and
duration, coupled with a biomarker-oriented
approach, are needed to better understand and stan-
dardize the use of ECT augmentation in the treat-
ment of schizophrenia.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
S.N.S. has nothing to disclose. G.P. reports grant support
from NIMH and the Stanley Foundation, and participa-
tion in clinical trial by Jansen and St. Jude Medical,
outside the scope of the submitted work. C.H.K. reports
grants from National Institute of Mental Health, royal-
ties from Cambridge University Press, personal fees from
UpToDate, Psychiatric Times and personal fees from
Northwell Health for teaching in an ECT course, outside
the scope of the submitted work.
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Volume 32  Number 00  Month 2018