Asian Journal of Psychiatry 22 (2016) 22–27

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Asian Journal of Psychiatry

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

Predominant mania course in Indian patients with bipolar I disorder

Sushma Bilichodu Rangappa, Shashidhara Munivenkatappa,
Janardhanan C. Narayanaswamy, Sanjeev Jain, Y.C. Janardhan Reddy *
Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India

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

Article history: Many long-term follow-up studies suggest that bipolar disorder (BD) is highly recurrent and that
Received 18 September 2015 depressive episodes are commoner than hypomania/manic episodes. However, some studies from
Received in revised form 3 March 2016 tropical countries including India suggest that the patients experience a greater proportion of manic
Accepted 16 April 2016
episodes than depressive episodes. The aim of the present study was to examine the course of BD type 1
Available online
(BD I) in a sample of hospitalized Indian subjects. We examined the clinical course of 285 BD I subjects
with at least 5 years of illness using standard life charting method. These subjects were hospitalized
Keywords:
between October 2010 and October 2012. The predominant polarity (having at least two-thirds of their
Bipolar disorder
Predominant polarity
lifetime episodes at one polarity) was mania (79%). Unipolar mania ( 3 mania episodes and no episodes
Unipolar mania of depression) was observed in 48% of the subjects. The frequency of rapid cycling course was noted in
Course 2.5% of the subjects. Predominant manic polarity group had the illness onset mostly with a manic
episode (88.9%) and the predominant depressive polarity group with a depressive episode (73.8%). Mania
was the predominant polarity with a high rate of unipolar mania and a majority of the subjects had
greater number of manic episodes than depressive/mixed episodes. The onset polarity determined the
predominant polarity during the course of illness. Predominantly, mania course could have significant
implications in the treatment of bipolar disorder.
ß 2016 Published by Elsevier B.V.

1. Introduction mood recordings, Kupka et al. reported that subjects with BD I

Bipolar disorder (BD) is a highly recurring illness (Angst and
Sellaro, 2000; Winokur et al., 1994). Recurrent episodes can be
both manic and depressive type but the NIMH long-term follow-up
studies of BD type I (BD I) have shown the predominance of
depressive episodes over manic/hypomanic episodes during the
course of the illness (Judd et al., 2002; Post et al., 2003). Studies
from other countries, including Spain, Germany, United States
have also reported that a majority of the patients with BD I spend a
greater proportion of their time in depressive phase than in the
manic phase (Baldessarini et al., 2012; Colom et al., 2006; Popovic
et al., 2014; Volkert et al., 2014). In the NIMH study, depressive
symptoms occupied about 32% of the follow up period, when
compared with manic/hypomanic symptoms which occupied less
than 10% of the follow up period (Judd et al., 2002). Using weekly
* Corresponding author at: Department of Psychiatry, National Institute of
Mental Health And Neurosciences (NIMHANS), Bangalore 560029, India.
Tel.: +91 8026995278.
E-mail address: ycjreddy@gmail.com (Y.C. Janardhan Reddy).
spent 36% of their time in depressed state, and this was nearly
three times more than the time spent in mania/hypomania (Kupka
et al., 2007). Similar findings with greater recurrences in the form
of depressive episodes have been demonstrated in Systematic
Treatment Enhancement Program for Bipolar Disorder cohort
(STEP-BD) (Perlis et al., 2006). Overall, depressive episodes are
reported to be three times more common than manic episodes in
BD 1 (Yatham and Maj, 2010).
Studies from the tropics suggest a significantly higher incidence
of mania in the course of BD. These studies from India, Hong Kong,
Fiji and Nigeria observe that the course is predominantly occupied
by manic episodes and that ‘‘unipolar mania’’ without occurrence of
any depressive episodes is not uncommon (Aghanwa, 2001; Chopra
et al., 2006; Khanna et al., 1992; Khess et al., 1997; Makanjuola,
1985; Yazici, 2014). Manic episodes accounted for 72% of all the
episodes in a study from India (Chopra et al., 2006), and in a study
from Nigeria, 55 out of 104 subjects studied had unipolar mania
(Makanjuola, 1985). A study from Israel also reported a predomi-
nantly manic course of illness (Osher et al., 2000). The predominant
polarity in the course of BD has important clinical implications, as
treatment of those subjects with predominant manic course could

http://dx.doi.org/10.1016/j.ajp.2016.04.006
1876-2018/ß 2016 Published by Elsevier B.V.
 S.B. Rangappa et al. / Asian Journal of Psychiatry 22 (2016) 22–27 23

differ from treatment of BD with mostly depressive episodes Table 1

Clinical profile and predominant polarity in subjects with bipolar disorder type 1
(Popovic et al., 2014; Volkert et al., 2014). We therefore examined
(N = 285).
the course of BD I in a large consecutive sample of hospitalised Indian
subjects by using a standard life charting method. N (%)/Mean
(Standard Deviation)

2. Method Current age (years) 33.6 (11.71)

Age at Onset (years) 22.1 (7.9)
Duration of Illness (years) 11.5 (7.9)
Inclusion criteria for the study included: 1) Consecutive adult
Gender, male 162 (56.8)
patients aged between 17 and 50 years with DSM-IV TR diagnosis Index Episode Polarity
of BD type I; 2) illness duration of at least 5 years; and 3) Mania 238 (83.5)
hospitalization for bipolar disorder. Patients with illness duration Depression 40(14)
Mixed 7 (2.5)
of at least 5 years were included because many naturalistic follow-
HAMD 23.9 (11.8)
up studies have shown that most subjects will have a relapse and YMRS 35.4 (6.04)
often multiple relapses within 4 5 years of index episode Number of hospitalizations 3.3 (2.3)
(Marneros and Breiger, 2002). Inclusion of patients with at least Comorbid Axis I disorders
5 years illness would help in better characterization of the course, Anxiety disorders 34 (11.9)
Alcohol and substance dependence 103(36.1)
rather than including patients with a shorter illness duration such
Comorbid Axis II disorders
1 or 2 years. Subjects admitted over a period of 2 years from Cluster A 8 (2.8)
October 2010 to October 2012 at the National Institute of Mental Cluster B 51 (17.9)
Health and Neurosciences (NIMHANS), Bangalore, India were thus Cluster C 14 (4.9)
Predominant polarity*
recruited for the study. Those with organic mood disorders and
Predominantly mania** 226 (79.3)
clinical evidence of mental retardation and dementia were not Unipolar Mania*** 137 (48.1)
included in the study. Subjects who participated in the study gave Predominantly depression 39 (13.7)
voluntary written informed consent and the NIMHANS Institute Mixed 3 (1.1)
Ethics Committee approved the study. Unclear 17 (6)
Rapid cycling 7 (2.5)
Four hundred and sixty subjects with a diagnosis of BD I were
screened. Out of these, 328 subjects met the study criteria, but HAMD-Hamilton Rating Scale for Depression; YMRS-Young Mania Rating Scale; BD-
Bipolar Disorder.
43 subjects refused consent, reducing the study sample to *
Predominant polarity - Classification of patients with bipolar disorder as either
285 subjects. Subjects were administered the Mini International predominantly depressed (PD) or predominantly manic (PM), as defined by having
Neuropsychiatric Interview (MINI) (Sheehan et al., 1998) to at least two-thirds of their lifetime episodes at one polarity or the other.
**
confirm the diagnosis of as well as to diagnose comorbid axis Predominant mania group also includes all the unipolar mania cases.
***
1 psychiatric disorders. Personality disorders were assessed using Unipolar mania:  three episodes of mania and no episodes of depression.

the Structured Clinical Interview for Axis II Disorders (First et al.,

1995). NIMH Life charting method was employed to assess the
course of BD (Roy-Byrne et al., 1985). The information for life
charting was collated from hospital medical records, clinical notes
from previous physicians, and personal interview of patient and
his/her immediate family member. The severity of mania and
depression were assessed using the Young Mania Rating Scale
(Young et al., 1978) and the Hamilton Rating Scale for Depression
(Hamilton, 1960) respectively and the global severity was
measured by the Clinical Global Impression, Severity scale (CGI-
S) (Guy, 1976). Family members were interviewed for the presence
of psychiatric disorders in the first degree relatives using the
Family Interview for Genetic Studies (FIGS) (Maxwell, 1992).
Subjects were classified as predominantly depressed (PD) or
predominantly manic (PM) if they had had at least two-thirds
of their lifetime episodes at one polarity or the other as per the
guidelines of the International Society for Bipolar Disorders (ISBD)
(Tohen et al., 2009).
3. Results
Table 1 depicts the socio-demographic and clinical profile of the
285 subjects who formed the sample of this study. It is evident that
a majority had predominantly manic course (79%) and unipolar
mania was present in less than a half of the sample (48%). Only 82
(29%) of the subjects were on continuous prophylaxis. Among
these 82 patients, 61% patients were on lithium carbonate, 17.1%
were on sodium valproate, 2.4% were on carbamazepine and 19.5%
were on more than one mood stabilisers.
Demographic and clinical characteristics based on predominant
polarity are shown in Table 2. Those with predominantly
depressed course spent more time in depression, had more
depressive episodes, and started the illness with depression. They
were somewhat overrepresented by women, had greater family
history of major depression and also displayed higher suicidal risk.
Those with predominant mania spent more time in mania and,
began their illness with mania. As can be seen in Table 3, those with
depressed course received more often antidepressants and electro-
convulsive therapy (ECT). Overall, percentage of time spent on
treatment was low in the sample. A comparison of unipolar mania
group (n = 137) and the others (n = 148) did not reveal any
significant differences.
4. Discussion
The main finding of this study is the predominance of manic
course in a majority of the subjects. Many of the previous studies
report that depression is the most common mode of recurrence
in BD, thus forming the predominant polarity of BD (Angst, 1978;
Judd et al., 2002; Kupka et al., 2007; Perlis et al., 2006; Post et al.,
2003; Yatham and Maj, 2010). For instance, in the NIMH
Collaborative Depression Study, patients with BD I experienced
depression much more frequently than hypomania or mania (Judd
et al., 2002). Similarly, 2-year prospective data from the Systematic
Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
cohort, showed that 72% of recurrences were depressive in nature
(Perlis et al., 2006). In the 26-year follow up of the Zurich cohort,
depressive mood episodes composed 51% of the mood episodes
(Angst, 1978). Results from the Stanley Foundation Bipolar
Network study revealed a similar finding that depression occupied
three times greater proportion of the course compared with mania
(Post et al., 2003). In the NIMH Collaborative Depression Study,
ratio of depression to mania in BP I was approximately 3:1 (Yatham
and Maj, 2010). Some of the other studies from Spain, Germany,
Unites States have also reported that a majority of the patients
with BD I spend a greater proportion of their time in depressive
24 S.B. Rangappa et al. / Asian Journal of Psychiatry 22 (2016) 22–27

Table 2
Demographic and clinical characteristics in bipolar I disorder based on predominant polarity.

Variable Predominantly mania (n = 226) Predominantly depression (n = 39) X2/t P

Mean (SD)/n (%) Mean (SD)/n (%)

Age, years 33.9 (12) 33. 7 (11.4) .120 .904

Gender, female 91 (40.3) 23 (59) 4.749 .029
Age at onset, years 22.3 (8.2) 21.6 (7.5) .537 .592
Duration of illness, months 139.3 (100.1) 142.8 (83.2) -.204 .833
CGI-S 3.8 (1.1) 3.8 (0.8) .517 .605
Family history
Bipolar disorder 49 (21.7) 9 (23.1) .038 .846
Major depression 17 (7.5) 10 (25.6) 10.03 .002
Psychosis 19 (8.4) 5 (12.8) .342 .559
Substance abuse 55 (24.3) 11 (28.2) .266 .606
Suicide 18 (8) 3 (7) - .954
1st episode polarity 82.12 <.001
Mania 201 (88.9) 7 (17.9)
Depression 22 (9.7) 29 (74.4)
Mixed 3 (1.3) 3 (7.7)
Index episode 63.293 <0.001
Mania 208 (92) 18 (46.2)
Depression 15 (6.6) 21 (53.8)
Mixed 3 (1.3) 0
Suicide risk* 36.09 <0.001
Low 210 (92.9) 23 (59)
Moderate 14 (6.2) 14 (35.9)
High 2 (.9) 2 (5.1)
% time in episodes 7.51 (9.16) 11.66 (9.56) -2.595 .01
% time in mania 6.33 (8.85) 2.73 (3.87) 4.206 <0.001
% time in depression 2.15 (8.22) 8.49 (6.41) -4.576 <0.001
Episodes
Mania 5.7 (9.9) 3.6 (6.6) 1.294 .197
Depression 1.8 (9.6) 5.9 (8.1) -2.472 .014
Rapid cycling 6 (2.7) 1 (2.6) .001 .974
Number of hospitalizations 3.2 (2.3) 4.4 (2.4) -2.97 .003
*
Low = one to eight, Moderate = 9 to 16, High  17 points on the suicidality section of the Mini International Neuropsychiatric Interview (MINI).

phase than in the manic phase (Baldessarini et al., 2012; Colom
et al., 2006; Popovic et al., 2014; Volkert et al., 2014).
Contrary to the general observation that patients with BD
experience more of depression than mania, some of the studies
from India (Chopra et al., 2006; Khanna et al., 1992; Khess et al.,
1997), Nigeria (Makanjuola, 1985), Ethiopia (Fekadu et al., 2006),
Israel (Osher et al., 2000) and Hong Kong (Lee, 1992) report that
mania constitutes a greater part of BD course than depression.
Our study confirms this observation. One can only speculate the
potential mediating effect of genetic differences and environmen-
tal factors such as sunlight and latitude in determining the
predominant course. BD has a strong genetic component and it has
been increasingly recognized that circadian rhythm abnormalities
could play an important role in the relapse and symptom
expression. For instance, variations in the CLOCK gene suggest
that CLOCK3111 T/C C/C allele is associated with a higher
recurrence rate (Benedetti et al., 2003). A CLOCK mutant mouse
might constitute an animal model of mania (Roybal et al.,
2007).Apart from these possible genetic differences, variations
in sunlight can also play a role (Bauer et al., 2015; Bauer et al.,
2014; Narayanaswamy et al., 2014). The countries where mania is
predominant are from lower latitudes where ambient sunlight
is greater. Indeed, such epigenetic influences affecting circadian
rhythm have been implicated in disease states (Masri and
Sassone-Corsi, 2013).
Unipolar mania has not been a common description in the
literature. Some of the previous studies have reported that
unipolar mania is characterized by female preponderance (Solo-
mon et al., 2003), earlier age at onset (Shulman and Tohen, 1994),
greater number of episodes (Khanna et al., 1992), premorbid

Table 3
Treatment characteristics in bipolar I disorder based on predominant polarity.

Variable Predominantly mania (n = 226) Predominantly depression (n = 39) X2/t P

Mean (SD)/n (%) Mean (SD)/n (%)

Past treatment
% time on mood stabilizers 12.10 (13.93) 13.41 (14.69) -0.539 0.590
% time on antipsychotics 12.57 (13.80) 14.38 (13.79) -0.755 0.451
% time on antidepressants 1.51 (3.94) 14.94 (15.43) -5.404 <0.001
Current treatment*
Lithium + atypical antipsychotics 143 (63.27) 26 (66.7) 0.116 0.734
Valproate + atypical antipsychotics 37 (16.4) 4 (10.3) 0.951 0.329
Lithium + Valproate + atypical antipsychotics 15 (6.6) 2 (5.1) 0.126 0.722
Lithium + Valproate 10 (4.4) 3 (7.7) 0.222 0.638
Antidepressants** 55 (24.3) 30 (76.9) 42.216 <0.001
Benzodiazepines** 175 (77.4) 22 (56.4) 7.706 0.006
ECT** 30 (13.3) 14 (35.9) 12.294 <0.001
*
Lamotrigine + lithium or valproate/atypical antipsychotic = 5, Carbamazepine + lithium or valproate/atypical antipsychotic = 10 >2 mood stabilizers = 5, Risperidone
alone = 2.
**
In combination with mood stabilizers and/or antipsychotic drugs.
 S.B. Rangappa et al. / Asian Journal of Psychiatry 22 (2016) 22–27
hyperthymia (Perugi et al., 2007; Yazici et al., 2002) and greater
occurrence of grandiosity (Abrams et al., 1979) and psychotic
symptoms (Pfohl et al., 1982) in addition to lesser occurrence of
rapid cycling phenomenon (Yazici et al., 2002). It is also interesting
to note that this entity has been described more frequently from
the ‘‘non-western’’ cultures (Lee and Yu, 1994). As demonstrated
in this study, a high frequency of recurrent unipolar mania has
been reported in previous studies from India (Khanna et al., 1992)
and Nigeria (Makanjuola, 1985).
The rate of rapid cycling in our sample is low (2.5%) which is
much below the year prevalence of 5 33% and lifetime prevalence
of 26 43% (Carvalho et al., 2014). There are several possible
reasons for low prevalence in our sample. Firstly, rapid cycling is
associated with first depressive episode and predominant depres-
sive polarity (Bauer et al., 2008; Carvalho et al., 2014) and use of
antidepressants (Bauer et al., 2008; Carvalho et al., 2014; Wehr and
Goodwin, 1979; Wehr et al., 1988). In our sample, the predominant
polarity was mania and most started their illness with manic
episode. In addition, time treated with antidepressants was
considerably less and when used always in combination with
mood stabilizers and/or antipsychotics (Table 3). Secondly, the
rates of rapid cycling reported in the literature could well be at the
upper limits of true prevalence because of the selection bias of
research centres (Bauer et al., 2008). Our sample is from the
inpatient services of a psychiatric hospital but not from special
bipolar disorder services. Special centres for bipolar disorder may
attract more severely ill patients that include rapid cyclers. Finally,
rapid cycling is more common in bipolar II disorder whereas our
sample is that of bipolar I type (Carvalho et al., 2014). This could be
one contributory factor although some studies refute association
between rapid cycling and bipolar types (Mackin, 2005; Maj et al.,
1994).
Predominant polarity during the course of bipolar disorder
seems to have important clinical and therapeutic implications.
Polarity of the first mood episode determined the predominant
polarity during the course. Turvey et al. reported that the polarity
sequences tend to remain stable over time (Turvey et al., 1999). In a
study by Perlis et al., 62% of patients whose initial episode was
mania had a predominantly mania course (Perlis et al., 2005).
Other studies have also demonstrated that initial episode polarity
determines the predominant polarity during the course, i.e. initial
episode of mania and depression determine the predominantly
manic and depressive course, respectively (Baldessarini et al.,
2012; Colom et al., 2006; Popovic et al., 2014).
Depressive polarity was also associated with a higher suicidal
risk and more number of hospitalizations suggesting a more severe
illness. Our findings are in accordance with the findings of other
studies which reported greater suicidal risk (Baldessarini et al.,
2012; Colom et al., 2006; Popovic et al., 2014) and more
hospitalizations (Popovic et al., 2014) in those with predominant
depressive polarity. Another interesting aspect is that predomi-
nant depressive group had a greater family history of depressive
disorder. Indeed, such independence in familial transmission
between manic and depressive phenotypes has been recently
demonstrated (Merikangas et al., 2014).
Patients in our sample on the whole were not on psychotropics
for most part of the course. For the index admission, lithium in
combination with atypical antipsychotics was the most preferred
option followed by combination of valproate and atypical
antipsychotics. These observations are in sharp contrast to
declining use of lithium and frequent use of valproate elsewhere
in the world (Baldessarini et al., 2007; Blanco et al., 2002).
Similarly, the use of antidepressants was limited in our patients
compared with the extensive use of antidepressants in the
treatment of bipolar disorder elsewhere. For example, most
commonly prescribed drugs in US patients was antidepressants
25
(Baldessarini et al., 2007) and often without concurrent mood
stabilizers (Baldessarini et al., 2007; Blanco et al., 2002; Moreno
et al., 2007). In our sample, those with depressive polarity were
treated more often with antidepressants and ECT. Previous studies
have reported that those with depressive polarity were more often
treated with antidepressants and lamotrigine (Colom et al., 2006;
Volkert et al., 2014) and ECT (Baldessarini et al., 2012), whereas
those with manic polarity were often treated with mood stabilizers
or antipsychotics (Colom et al., 2006; Volkert et al., 2014).
Findings of our study could have significant clinical and
research implications. The reported predominance of depression
in the course of bipolar disorder has prompted the conclusion that
BD I is predominantly a depressive illness, and that BD II is almost
exclusively a chronic depressive illness (Yatham and Maj, 2010). It
is possible that the long-term course of BD in tropics may not be
similar to that reported in previous western studies. There is
preliminary evidence that this may be the case even in juvenile
bipolar disorder (Jairam et al., 2004; Rajeev et al., 2004). Mood
stabilizers (valproate and lithium) are mostly effective in
preventing manic relapses; therefore, ensuring treatment adher-
ence with mood stabilizers may vastly improve the prognosis
(Pompili et al., 2009). It is reassuring that depression was not the
predominant polarity in our sample since treatment of bipolar
depression is challenging with a possible risk of worsening the
course with the use of antidepressants (Ghaemi et al., 2003) and a
high risk of weight gain and metabolic syndrome with the long-
term use of olanzapine and quetiapine (Newcomer, 2007). Those
with initial episode of depression may benefit from the use of drugs
such as lamotrigine and lurasidone whereas those with initial
episode of mania may benefit from mood stabilizers and certain
atypical antipsychotics. It is in this context the predominant
polarity has important treatment implications.
The subjects in the study were evaluated using a retrospective
life charting method and this may be a source for potential recall
bias. Studying hospitalized sample could have resulted in the
evaluation of a severely ill population, thus limiting the
generalizability. Mild depressive episodes may have been under-
reported. However, a meticulous examination of the course
through standardized life charting method and thorough corrobo-
ration of the history with the aid of an accompanying family
member have helped us to overcome these limitations to some
extent. Course of bipolar disorder in the India and other tropical
countries need to be systematically examined using multiple data
sets, and if confirmed, the reasons for this difference in semiology
need to be understood. It could offer an insight into the biological
and environmental correlates, and thus improve our understand-
ing and therapeutics of the syndrome.
Conflict of interest
none
Funding source
nil
Acknowledgments
The authors would like to acknowledge the participants of this
study for their valuable time and co-operation. This is a non-
funded study.
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