Asian Journal of Psychiatry 5 (2012) 11–17

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Asian Journal of Psychiatry

journal homepage: www.elsevier.com/locate/ajp

Review

Electroconvulsive therapy (ECT) in bipolar disorder: A narrative review of

literature
Jagadisha Thirthalli *, M. Krishna Prasad, Bangalore N. Gangadhar
Department of Psychiatry, National Institute of Mental Health & Neurosciences, Bangalore 560029, India

A R T I C L E I N F O A B S T R A C T

Article history: In many countries including India electroconvulsive therapy (ECT) is frequently used to treat different
Received 9 February 2010 phases of bipolar disorder. The response to ECT is impressive in mania, depression and in mixed affective
Received in revised form 4 November 2011 states. Preliminary evidence also suggests benefit from maintenance ECT in bipolar disorder. However,
Accepted 12 December 2011
most of the literature on efficacy and adverse effects comes from case series, retrospective reports and
open trials – controlled trials have been few and far between. Official guidelines recommend the use of
Keywords: ECT only when there is a dire emergency or when all other options have been exhausted. Concurrent use
Bipolar disorder
of lithium and antiepileptic drugs along with ECT is common in clinical practice. While such practice
Electroconvulsive therapy
Lithium
appears to be largely safe, one should be mindful about dose of lithium and possible interference of
Antiepileptic drugs antiepileptic drugs with efficacy of ECT. The use of suprathreshold bilateral ECT and bifrontal placement
Mania of electrodes may confer some advantage over other methods.
ß 2011 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2. Electroconvulsive therapy (ECT) in mania . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
3. ECT in bipolar depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4. ECT in mixed affective episodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
5. Special issues of ECT in bipolar disorder (BD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
5.1. ECT in treatment resistant BD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
5.2. ECT in rapid cycling BD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
5.3. ECT in continuation and maintenance treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
6. Concurrent use of medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
6.1. Lithium & ECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
6.2. Antiepileptic drugs (AED) & ECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
6.3. Other medications and ECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
7. Electrode placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
8. Electrical dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
9. Adverse effects of ECT in BD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
10. Research on mechanisms of action of ECT in BD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
11. Patients’ attitude towards ECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
12. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

1. Introduction

Bipolar disorder (BD) is typically diagnosed in young adulthood

and causes serious problems throughout life – with a lifetime
prevalence of 0.2–1.2% (Helgason, 1979; James and Chapman,
* Corresponding author. Tel.: +91 8026995350; fax: +91 8026564830. 1975; Weissman et al., 1988; Weissman and Myers, 1978), it is one
E-mail address: jagatth@yahoo.com (J. Thirthalli). of the top disabling medical conditions known to mankind. 7–19%

1876-2018/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ajp.2011.12.002
12 J. Thirthalli et al. / Asian Journal of Psychiatry 5 (2012) 11–17

of those affected with BD end their lives (Angst et al., 2002;
Goodwin and Jamison, 1990), which is 15 times greater than the
general population (Harris and Barraclough, 1997). Though several
effective treatment options are available, the scene is far from
being satisfactory. Many patients with BD remain refractory to
treatment. Even with medication adherence, breakthrough epi-
sodes are common. Electroconvulsive therapy (ECT) is one of the
oldest known treatment options that is known to be useful in both
manic and depressed phases of BD. It has a unique place in the
psychiatric armamentarium for tackling different challenges of BD
– it is useful as an acute treatment of severe depression, mania and
mixed affective states, in highly suicidal patients, in those
presenting with catatonia, and in those with treatment refractory
illness. It is found to be useful as a prophylactic option as well in
BD. In this article, we review literature regarding the use of ECT in
BD. There are very few systematically conducted research studies
addressing several clinically important issues, including efficacy of
ECT in different phases of BD, consequences of co-administration of
different medications and ECT, the role of maintenance ECT, etc. In
this background, we did not undertake a systematic review. This
narrative review is based on literature from several sources,
including textbooks/handbooks on ECT (e.g., Abrams, 2002; Scott,
2005), taskforce reports (e.g., American Psychiatric Association,
2001), original research papers and reviews.
2. Electroconvulsive therapy (ECT) in mania
ECT is frequently used in treating mania across the globe. Fairly
high proportions of inpatients with mania receive ECT in different
parts of the world. In a Canadian epidemiological study 20% of
manic inpatients received ECT (Malla, 1986). A naturalistic study
on the treatment of acute mania in the US reported rates of 8.5%
amongst 438 patients hospitalized for mania, over a 12 year period
(Black et al., 1987). ECT was used in 33.2% of the admissions for
mania in a naturalistic evaluation from a private Brazilian
psychiatric hospital (Volpe et al., 2003). Mania is the third most
common indication for ECT following psychotic depression and
catatonic schizophrenia in some centers (Gill and Lambourn, 1979;
Vanelle et al., 2008). In a survey of the practice of ECT in Asia
(Chanpattana et al., 2009), schizophrenia (41.8%) and major
depression (32.4%) were the major indications for ECT followed
by mania (14%). Studies examining the efficacy of ECT in acute
manic episodes are shown in Table 1.
The majority of the available evidence is from naturalistic
studies and retrospective chart reviews, with their inherent
methodological limitations. In our literature search we found
only one randomized trial (Small et al., 1988) that has compared
ECT with lithium and another trial (Sikdar et al., 1994) that has
compared ECT and sham ECT each in combination with chlor-
promazine. A third randomized trial compared ECT with a
combination of Lithium and Haloperidol (Mukherjee et al.,
1988). The available evidence suggests that in patients with
mania, ECT is as effective as or more efficacious than medications,
including lithium, chlorpromazine and their combination. Further,
it seems to reduce the duration of hospitalization (McCabe, 1976)
and to delay rehospitalization (Thomas and Reddy, 1982). It is
noteworthy that the apparent superiority of ECT over pharmaco-
logical alternatives is particularly prominent in patients with
mixed episodes and severe mania. Adverse effects have received
scant attention in these studies. Except for Ikeji et al. study (1999)
none of the studies presented in the Table 1 have systematically
assessed cognitive functions or other side effects. We did not find
any study comparing the efficacy of ECT with that of atypical
antipsychotics or valproate in mania.
Consistent and significant benefit for ECT has been found in
delirious mania (Karmacharya et al., 2008). Among patients with
mania who receive ECT-antipsychotic combination, younger
patients with greater severity of mania and treatment-resistant
mania are less likely to achieve remission (Thirthalli et al., 2008). It
may be noted that some of these features are predictors of poor

Table 1
Studies examining the efficacy of ECT in acute manic episodes.

Study Design Sample Comparison Findings

McCabe (1976)
McCabe and Norris (1977)
Thomas and Reddy (1982)
Black et al. (1987)
Small et al. (1988)
Mukherjee et al. (1988)
Sikdar et al. (1994)
Small et al. (1996)
Ikeji et al. (1999)
Chart review
Chart review
Chart review
Naturalistic study
Randomized trial used both
blind and non blind raters
Randomized trial, raters
blind to ECT conditions
Randomized trial; used
double blind ratings
Pooled data of sequential
trials of various therapeutic
modalities
Naturalistic study
28 in each group Untreated matched control group ECT associated with better condition
at discharge, lesser duration of
hospitalization, and greater social
recovery
28 in each group Chlorpromazine, no treatment ECT & Chlorpromazine superior to
no treatment; 10 Chlorpromazine
non responders recovered with ECT
n = 299 28% Antipsychotics (33%) & Lithium ECT delayed readmission
received ECT (10%) other convulsive therapies
or conservative treatment (57%)
n = 438 Therapeutic and sub-therapeutic ECT significantly better than both
lithium
n = 34 Lithium and Chlorpromazine ECT better than lithium in the first
8 weeks; difference between
Lithium and ECT best in mixed
episodes & severe mania
n = 20, treatment Rightt (8), Left (5) unilateral 59% of the ECT treated patients
resistant manics ECT, bilateral ECT(7) responders, no difference between
unilateral and bilateral ECT
n = 30 Chlorpromazine + ECT vs. Chlorpromazine & ECT group showed
Chlorpromazine + Sham ECT greater and faster improvement than
Chlorpromazine & sham ECT group
n = 130, n = 34 for ECT, Lithium, Carbamazepine, ECT & sparing use of neuroleptics
Lithium ECT combinations with neuroleptics had the best response, followed by
comparison a combination of lithium &
neuroleptics; Lithium or carbamazepine
monotherapy less effective
n = 70, 29% manic Unmodified ECT vs. ECT patients recovered by 2 months;
patients pharmacotherapy steady cognitive improvement with
clinical recovery; ECT group had more
treatment resistant disorders
 J. Thirthalli et al. / Asian Journal of Psychiatry 5 (2012) 11–17
response to pharmacotherapy as well (Dilsaver et al., 1993; Welge
et al., 2004). In studies, which compared ECT and medications
(Small et al., 1988; Volpe et al., 2003), those with violent and severe
mania, psychotic features, worse chronicity indices (more epi-
sodes, longer durations), catatonia and mixed episodes had
particularly better response to ECT than to medications. While
Small et al. (1988) found this in a prospective comparative study
involving 34 patients with mania/mixed episodes, similar obser-
vations were made by Volpe et al. (2003) in a paper describing the
treatment of mania/mixed episodes in a Brazilian hospital, in
which they studied the naturalistic outcome of 425 admissions.
Overall, though research on the use of ECT in mania is limited,
ECT has been accepted as being highly effective, with 80% of the
cases remitting or showing marked clinical improvement
(Mukherjee et al., 1994; Rey and Walter, 1997). Guidelines
(American Psychiatric Association, 2001; National Institute for
Clinical Excellence, 2003; Scott, 2005) recommend the use of ECT
in treating manic episodes only when the condition is considered
potentially life threatening (e.g., from physical exhaustion) or
when the condition remains resistant to pharmacological treat-
ment. However, in many countries it is used quite frequently for
less severe conditions also. This is partly because of the conjecture
that ECT brings about faster response in acute mania, in turn
reducing the dosage of medications and duration of inpatient stay
(Hiremani et al., 2008). In the absence of any research to support
this conjecture, research examining the relative cost-effectiveness
and adverse effects of ECT vis-à-vis medications in less severe cases
of mania are needed. Substantial proportion of patients with mania
would be disinclined to cooperate for any form of treatment;
getting such patients to consent for random assignment to ECT or
drugs would pose a major challenge in planning such studies
(Abrams, 2002), though notable examples of such studies do exist
(Sikdar et al., 1994).
3. ECT in bipolar depression
To the best of our knowledge no controlled trial has examined
the efficacy of ECT in bipolar depression. ECT has been reported to
have the highest response rate of all treatments for acute bipolar
depression (Kalin, 1996). Bipolar depression has been noted to
have a faster response than unipolar depression and to require
fewer treatments (Daly et al., 2001). This study did not analyze the
response in bipolar I and bipolar II depression separately. Similar
results have been reported with ultra brief pulse ECT in a study that
randomized bipolar and unipolar depressives to receive bifrontal
or unilateral ECT (Sienaert et al., 2009). When compared to
unipolar depression and bipolar II, bipolar I depressives showed
the worst results in terms of remission rate and they also tended to
exhibit residual manic and psychotic symptomatology (Medda
et al., 2009). However, this sample included patients who were
resistant to pharmacological treatment. The authors of this paper
proposed that other clinical or psychopathological states that co-
varied with diagnostic subtypes were responsible for the differ-
ence in response such as greater mixed-psychotic symptomatology
Table 2
Studies examining the efficacy of ECT in mixed affective episodes.
Study Design n of mixed mania
Ciapparelli et al. (2001) Prospective clinical 41 with mixed mania
trial in treatment
resistant patients
Gruber et al. (2000) Case series 7 Medication refractory
mixed mania patients
Devanand et al. (2000) Chart review Bipolar mixed (n = 10)
13
in the bipolar I patients. A chart-review also reports that there is a
poorer subjective response to ECT in bipolar depression compared
to unipolar depression (Hallam et al., 2009).
Guidelines (American Psychiatric Association, 2001; National
Institute for Clinical Excellence, 2003; Scott, 2005) do not
differentiate bipolar from unipolar depression and the indications
remain the same in both. ECT is recommended in emergency
treatment needing rapid & definitive response, high suicidal risk,
and severe psychomotor retardation, associated problems of eating
and drinking or physical deterioration. It is also recommended in
patients with treatment resistance, pregnant women with
depression, in patients with good response to ECT and poor
response to drugs in their past episodes. Patients may also choose
ECT as treatment for their bipolar depression.
4. ECT in mixed affective episodes
A recent systematic review found ECT to be an effective, safe,
and probably underutilized treatment of mixed states (Valenti
et al., 2008). The review found only 3 studies that met the authors’
quality criteria (Ciapparelli et al., 2001; Devanand et al., 2000;
Gruber et al., 2000); in all 3 studies, patients with mixed affective
states experienced substantial improvement with ECT. One case-
series including 7 medication-refractory patients with mixed
affective episodes found that all of them achieved remission with
ECT (Gruber et al., 2000); in the two other studies, the authors
compared response of patients with mixed affective episodes with
that of patients with bipolar depression using prospective
(Ciapparelli et al., 2001) and retrospective (Devanand et al.,
2000) designs. The latter study included medication refractory
patients with mixed episodes and a small number of patients with
mania too. While Ciapparelli et al. (2001) study suggested that
patients with mixed affective states improved faster than those
with depression, Devanand et al. (2000) found some evidence in
the opposite direction – patients with mixed affective states
required more ECT sessions and longer hospital stay. Since the
methodologies used in these studies were very different, it is hard
to delve much on the reason for the apparently contradictory
findings. Moreover, in none of these was efficacy of ECT compared
with that of a comparison treatment. Hence, these do not provide
definitive evidence for the usefulness of ECT in mixed episodes.
There is a need to examine this issue using randomized controlled
design, as many patients with mixed episodes continue to receive
ECT.
The 3 studies are summarized in Table 2.
5. Special issues of ECT in bipolar disorder (BD)
5.1. ECT in treatment resistant BD
Though working definitions have been provided for treatment
resistant bipolar depression, mania and mood cycling (Sachs,
1996) these have not been validated. Hence the true magnitude of
the problem is not available. As is the case with bipolar
Comparison Findings
23 patients with Mixed mania group exhibited a more
bipolar depression rapid and marked response
Not applicable All patients remitted
Bipolar depressed (n = 38), All 3 groups showed robust response;
bipolar manic (n = 5) longer hospital stays & greater number
of ECT treatments in mixed group
14 J. Thirthalli et al. / Asian Journal of Psychiatry 5 (2012) 11–17
depression, we did not find comparative studies examining the
use of ECT in this population. However, several case series have
found substantial benefits of using ECT in them (Ciapparelli et al.,
2001; Macedo-Soares et al., 2005; Soares et al., 2002). A chart
review and a concomitant literature review found that continua-
tion/maintenance ECT is effective in treatment resistant BD
(Vaidya et al., 2003). The magnitude of response reported in these
difficult-to-treat patients is quite impressive. For instance,
Macedo-Soares et al. (2005) reported that all six of their patients
with resistant BD responded to ECT. This underlines the need for
clinical trials comparing ECT and alternative treatments in
refractory BD.
5.2. ECT in rapid cycling BD
Rapid cycling has been considered a distinct course modifier
of BDs in the DSM-IV (American Psychiatric Association, 1994).
About 20% of patients with BD experience a period of time where
they meet criteria for rapid-cycling (Elhaj and Calabrese, 2005).
Literature regarding the role of ECT in rapid cycling BD is again
confined to case reports. Some authors have found ECT to be the
inducer of rapid cycling (Kukopulos et al., 1983) and others have
found the treatment to be ineffective in this condition (Wehr
et al., 1988). However, there are several reports of ECT being
effective in controlling rapid cycling BD (Berman and Wolpert,
1987; Kho, 2002). As rapid cycling is not uncommon, is difficult
to treat, and may adversely affect the outcome of BD, systematic
studies of ECT are required to systematically examine its role in
this condition.
5.3. ECT in continuation and maintenance treatment
Continuation and maintenance ECT may, on occasions, be the
only means of extending the period of euthymia and also of
providing prophylaxis in patients with medication resistant BD.
Systematic research in this area is sorely lacking. Most literature
on this topic is in the form of case reports (Barnes et al., 1997;
Chanpattana, 2000; Gupta et al., 1998) or case series of mixed
group of patients, including those with BD (Matzen et al., 1988;
Schwarz et al., 1995; Vanelle et al., 1994). We could find only one
report (Vaidya et al., 2003) of a case series involving 8 BD patients
in whom the number of maintenance ECT sessions ranged from 25
to 178. In all these reports, continuation/maintenance ECT was
used to treat medication-refractory BD. All reports were consis-
tent in that ECT was considered to be highly beneficial in these
difficult-to-treat patients: it effected maintenance of remission
(Gupta et al., 1998; Barnes et al., 1997; Chanpattana, 2000;
Vanelle et al., 1994) and reduction in the frequency of hospitali-
zation (Matzen et al., 1988; Schwarz et al., 1995). These
encouraging experiences, at the minimum, provide enough
preliminary evidence to warrant controlled studies in this
important area of research.
6. Concurrent use of medications
6.1. Lithium & ECT
Certain situations may warrant a combination of lithium and
ECT. Occasionally, patients on lithium who develop breakthrough
episodes may require ECT. Patients started on lithium may require
ECT before the effect of lithium starts, if the manic symptoms are
quite severe. An occasional patient on maintenance ECT may be
prescribed lithium. Several adverse interactions are feared, such as,
the consequences of increased blood-brain barrier permeability
leading to lithium toxicity, delirium, increased cognitive side
effects and prolonged seizures (American Psychiatric Association,
2001). Prolonged apnea may develop as a consequence of lithium-
succinylcholine interaction (Hill et al., 1976). Most observations
about the combination derive from case reports, case series and
retrospective comparative studies (Dolenc and Rasmussen, 2005;
Jha et al., 1996; Sartorius et al., 2005). Systematic evidence is
lacking; guidelines differ in their recommendations – while some
suggest lowering the energy of current during ECT (Scott, 2005),
others suggest either stopping or reducing the dose of lithium
(American Psychiatric Association, 2001).
In a prospective comparison of consecutive patients receiving
ECT with (n = 27) or without (n = 28) concomitant lithium, the
combination was found to be safe (Thirthalli et al., 2011) – there
were no instances of post-ECT delirium or prolonged confusion;
incidents of prolonged seizures were comparable in both groups.
However, this study was conducted on relatively young patients
without comorbid medical problems. Succinylcholine was the
muscle relaxant (0.5–0.75 mg/kg). Apnea time was longer than
6 min in higher proportion of ECT sessions of patients on lithium
and this was trend-worthy (p = 0.06). A direct correlation was
observed between lithium levels and time to recover from the
effects of anesthesia [partial correlation coefficient (after control-
ling for age) = 0.44; p = 0.028]. It is hence advisable to adjust the
serum lithium level to be at the lower end of therapeutic range in
patients who are referred for ECT.
6.2. Antiepileptic drugs (AED) & ECT
The idea of combining ECT with AEDs seems counterintuitive
at the outset but as with lithium, there may be several clinical
situations when this combination cannot be avoided. In a case
series of nine bipolar depression patients, lamotrigine and ECT
combination did not affect the ECT parameters and there was no
increase in adverse effects (Penland and Ostroff, 2006). The study
involved nine patients with acute bipolar depression who were
simultaneously treated with a course of ECT while titrating
lamotrigine for maintenance therapy. The use of lamotrigine in
upward titrated doses with ECT was uneventful and all patients
achieved remission. Anticonvulsants shorten ECT seizure dura-
tion, but there are no additional risks (Zarate et al., 1997). This
study compared the charts of 7 patients who received ECT and
valproate or carbamazepine with an ECT alone control group.
AEDs can potentially increase the seizure threshold. We did not
find prospective trials that studied the therapeutic efficacy or
interactions of the combination AEDs with ECT. Virupaksha et al.
(2010) recently completed a chart-review of 201 consecutive BD
patients who received bilateral ECT. Those on concomitant AED
(n = 79) had higher seizure threshold and shorter duration of
seizures than those who were not on AED (n = 122). The clinical
outcome was similar at the end of the ECT course with or without
concomitant AED. Those with concomitant AED required a
greater number of ECT sessions (mean = 7.9) than those
without AED (mean = 6.3; p < 0.01), suggesting that AED may
interfere with the efficacy of ECT. As patients on concomitant
AED receive higher electrical charges, it would be of interest to
examine if this is associated with greater cognitive adverse
effects. However, this has not been studied so far. The APA task
force (American Psychiatric Association, 2001) recommends
reducing the dose or stopping the drug completely if a
patient is on an AED for mood stabilization. If AEDs are for
epilepsy then reducing the dose or skipping the morning dose is
recommended. It is also recommended to maintain the plasma
level at the lower end of the therapeutic range, to provide EEG
monitoring during ECT and to consider a lower dose of
thiopentone. Very little empirical evidence is available to
support these guidelines. This underscores the need for
systematic studies in these aspects.
 J. Thirthalli et al. / Asian Journal of Psychiatry 5 (2012) 11–17
6.3. Other medications and ECT
Concurrent use of antidepressant drugs with ECT have not
conferred any advantage in unipolar depression, but may only
increase adverse effects (Mayur et al., 2000). This may apply to
bipolar depression as well, in addition to possibly precipitating
mania. Cautious use without a wash out period is recommended
for monoamine oxidase inhibitors (Dolenc et al., 2004). Concurrent
antipsychotic medications have benefits in schizophrenia in terms
of short term improvement (Klapheke, 1993; Nothdurfter et al.,
2006) and we speculate that this is true of patients with mania who
are prescribed ECT. Benzodiazepines, when clinically feasible, may
be avoided (American Psychiatric Association, 2001), as they may
decrease seizure duration (Boylan et al., 2000) and may diminish
the effect of ECT (Greenberg and Pettinati, 1993; Pettinati et al.,
1990).
7. Electrode placement
A retrospective study found that patients with severe features
of mania had failed to respond to right unilateral ECT but benefited
when they were switched to bilateral treatment (Small et al.,
1985). In a prospective study of hospitalized manic patients on
ECT, therapeutic responses were delayed until after switchover to
bilateral treatment from unilateral (Milstein et al., 1987). Overall, it
appears that unilateral ECT may be less effective than bilateral ECT
in mania.
Within bilateral ECT, bifrontal electrode placement is as
effective as bitemporal in depression with lesser cognitive side-
effects (Abrams and Taylor, 1976; Bailine et al., 2000; Heikman
et al., 2002; Letemendia et al., 1993; Ranjkesh et al., 2005). A
double-blind randomized trial that compared bifrontal (n = 19)
and bitemporal (n = 17) electrode placements in acute mania
reported that patients in the bifrontal group recovered significant-
ly faster, though comparable proportions improved in both groups.
No mood stabilizers were used in either group; the use of
concomitant antipsychotics and PRN medications were compara-
ble between the groups (Hiremani et al., 2008). These results are
consistent with similar reports about superior efficacy of bifrontal
ECT in depression and schizophrenia (Phutane, 2008). The
superiority of bifrontal ECT in limiting cognitive adverse events
was found in this study too, but the sample was too small to detect
a significant difference. Superior efficacy of bifrontal over
bitemporal ECT is unlikely due to greater seizure generalization,
as the cardiovascular response during ECT (heart rate, blood
pressure, and rate-pressure product) was comparable between the
two groups (Thirthalli et al., 2007).
8. Electrical dose
The recommendation by Royal College of Psychiatrists is to
administer 1.5 times the threshold electrical stimulus for bilateral
ECT (Scott, 2005). However, very little literature exists on the use
of electrical doses at different values relative to seizure threshold
during bilateral ECT. (Thirthalli et al., 2009) compared the charts
of patients who received bilateral ECT at threshold dose and at 1.5
times threshold dose. Patients with mania recovered faster with
1.5 times than with threshold stimulus – they received, on an
average, about two ECT less to achieve comparable clinical
improvement. In patients with depression and schizophrenia, the
difference in electrical dose effected little difference. However, a
randomized controlled trial by (Mohan et al., 2009) found that
bilateral, ECT delivered at stimulus intensities ‘just above’ the
individually titrated seizure threshold was as effective and safe as
ECT administered at stimulus intensities 2.5 times seizure
threshold in acute mania. The interventions did not differ
15
significantly in the time or number of ECT treatments required
for improvement or remission (Mohan et al., 2009). This apparent
contradiction could be because of methodological differences –
the former study compared ‘threshold’ versus ‘1.5 times
threshold’ level doses; the latter study compared ‘just above
threshold’ versus ‘2.5 times threshold’ level doses. The ‘just above
threshold’ patients received ECT at 30 mC above their seizure
threshold. In how many patients this was actually 1.5 times or
more of their threshold is not clear. Dosage greater than 1.5 times
threshold may not confer additional advantage; this may explain
the comparable efficacy of the two doses in Mohan et al. (2009)
study.
9. Adverse effects of ECT in BD
Switching from depressed to manic phase is known with the
use of ECT. In a series of 94 depressed patients (unipolar, bipolar
and schizo-depression) treated with ECT, 6 (64%) developed mania.
Earlier age of onset, more previous admissions and a longer
duration of illness are associated with the switch to mania (Lewis
and Nasrallah, 1986). Occurrence of ultra-rapid-cycling during
treatment of bipolar depression with ECT has also been reported
(Zavorotnyy et al., 2009). Some authors have highlighted the need
to differentiate emergence of mania from organic euphoric states,
which is characterized by predominant cognitive impairments and
the presence of inappropriate laughter (Devanand et al., 1988).
There are no specific guidelines for management of ECT-emergent
mania; practitioners differ in their approach to this situation:
while some continue with ECT, others suspend ECT and treat
symptoms, if they persist, with further ECT or appropriate
pharmacotherapy (American Psychiatric Association, 2001). Youn-
ger bipolar patients may be at higher risk for prolonged seizures
and the seizure threshold may be lower in manic patients than
depressive patients (Mukherjee et al., 1994). Status epilepticus has
been reported with the use of ECT in a pregnant woman with BD
(Balki et al., 2006).
10. Research on mechanisms of action of ECT in BD
Anticonvulsants are useful in the treatment of BDs; as the
seizure threshold increases and seizure duration decreases
through the course of ECT (Sackeim, 1999), it can be inferred
that ECT itself is an anticonvulsant. Since proportional increase
in seizure threshold has been observed to be significantly
greater in manic patients who responded to ECT than in those
who did not, Mukherjee (1989) has suggested that anticonvul-
sant effect of ECT could be responsible for its anti-manic
effect. Magnitude of decrease in cerebral blood flow covaries
with increase in seizure threshold through the course of ECT;
the latter serves as a reflection of an increase in cortical
inhibitory mechanisms (Sackeim, 1999). As decrease in cerebral
blood flow has been shown to be associated with response to
ECT in mania, irrespective of the electrode placement, it may be
inferred that increased cortical inhibitory mechanisms (GABAer-
gic transmission and increased endogenous opioid peptides)
may have a role in the anti-manic effect of ECT (Mukherjee,
1989). Further, ECT may increase permeability to antipsychotic
medications by lowering the blood–brain barrier (Sikdar et al.,
1994).
11. Patients’ attitude towards ECT
Majority of patients and relatives found ECT to be beneficial,
and maintained a positive attitude toward its use in BD (Virit et al.,
2007). There are no other studies available that have focused on
patient’s perspectives on ECT specifically in BD.
16 J. Thirthalli et al. / Asian Journal of Psychiatry 5 (2012) 11–17
12. Summary
Narrative nature of this review precludes us from making firm
conclusions on several aspects of ECT in BDs. This drawback
notwithstanding, a few observations merit attention of clinicians
and researchers in this field. A substantial proportion of patients
with BD receive ECT world over. Despite this, there is a striking lack
of systematic studies in this field. ECT appears to be highly effective
in both phases of BD; it also shows promise in treating challenging
situations like rapid cycling and treatment resistant BD. Some
special considerations merit attention. Bifrontal electrode place-
ment and stimulus 1.5 times threshold can optimize the benefits.
Lowering concomitant lithium or AEDs can have potential
advantage. Most research in this regard is either retrospective
or record-based. GABAergic mechanisms may explain therapeutic
effects of ECT in BD. Systematic research should be encouraged in
this field. Such an effort has potential to provide evidence-base for
the clinical utility of this important treatment tool in one of the
most challenging psychiatric conditions. Such research can also
provide useful insight into the neurobiology of BD as well as
mechanism of action of ECT.
Conflict of interest
None to declare.
Role of funding sources
The work was not funded.
Contributors
All authors contributed equally to the conceptualization and
writing up of the paper.
Acknowledgements
None.
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