Journal of Affective Disorders 173 (2015) 255–260
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Research report
Long term course of bipolar I disorder in India: Using retrospective life chart method Subramanian Karthick, Shivanand Kattimani n, Ravi Philip Rajkumar, Balaji Bharadwaj, Siddharth Sarkar Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
art ic l e i nf o
a b s t r a c t
Article history: Received 12 September 2014 Received in revised form 30 October 2014 Accepted 31 October 2014 Available online 13 November 2014
Background: There are grounds to believe that the course of bipolar disorder may be different in tropical countries such as India when compared to temperate nations. There is a dearth of literature about the course of bipolar I disorder from India. Methods: This study was conducted in a multispecialty teaching hospital in southern India. Patients with a DSM-IV TR diagnosis of bipolar I disorder, confirmed using SCID-I, with a minimum duration of illness of 3 years were assessed. Information was gathered on demographic and clinical variables, and the life course of episodes was charted using the National Institute of Mental Health – Life Chart Methodology Clinician Retrospective Chart (NIMH-LCM-CRC). Results: A total of 150 patients with bipolar disorder were included. The mean age at onset of illness was 24.8 ( 78.2) years. Mania was the first episode in a majority (85%) of the cases, and was the most frequent episode in the course of the illness, followed by depression. Patients spent an average of 11.1% of the illness duration in a mood episode, most commonly a manic episode. The median duration of manic or depressive episode was 2 months. Median time to recurrence after the first episode was 21 months (inter-quartile range of 10–60 months), and was shorter for women than men. Limitations: The hospital based sample from a particular region limits generalizability. Recall bias may be present in this retrospective information based study. Medical illness, personality disorders, other Axis I psychiatric disorders (apart from substance use disorder) and influence of adherence to treatment on the course of the disorder were not assessed systematically. Conclusions: Bipolar I disorder among Indian patients has a course characterized by predominantly manic episodes, which is in line with previous reports from tropical countries and substantially different from that of temperate regions. & 2014 Elsevier B.V. All rights reserved.
Keywords: Bipolar disorder Follow-up studies Prognosis Psychiatric status rating scales Gender India
1. Introduction Bipolar disorder is a severe chronic psychiatric disorder associated with considerable morbidity (Gitlin et al., 1995; Goldberg and Harrow, 2005). The course of this disorder is characterized by recurrent relapses, the frequency of which can be reduced with the help of effective medications (Grandjean and Aubry, 2009; Smith et al., 2007). A wide variation exists among individuals with bipolar disorder in terms of the course of illness. Characterizing the course of bipolar disorder can be helpful in understanding the impact of this illness on the patient and society. Such characterization is also helpful when planning therapeutic and service modalities for patients with this disorder (Yatham et al., 2013).
n
Corresponding author. E-mail address: [email protected] (S. Kattimani).
http://dx.doi.org/10.1016/j.jad.2014.10.056 0165-0327/& 2014 Elsevier B.V. All rights reserved.
The recently conducted World Mental Health survey found that the prevalence of bipolar spectrum disorder is 0.1% in India (Merikangas et al., 2011), of which bipolar I disorder accounts for approximately 20%. This estimate translates to a patient load of about 0.2 million individuals with bipolar I disorder. It has recently been suggested that the course of bipolar disorder may be different in tropical countries like India with a preponderance of manic episodes (Narayanaswamy et al., 2014), as compared to the temperate developed nations from where the majority of the published literature on bipolar disorder has emerged. If such differences in the types of episodes exist, they would have contextual implications in the management and service delivery focus of this vast patient population. There is a paucity of research about the course of bipolar disorder in tropical countries including India. Though studies in the west have progressed from chart based studies to long term cohorts including assessment of weekly mood state by 6 monthly retrospective recalls (Judd et al., 2003, 2002), there is a lack of
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longer term studies of the course and outcome of adults with bipolar disorder from India, and sample sizes in these studies have generally been small (Chopra et al., 2006; Khanna et al., 1992; Khess et al., 1997). In the absence of prospective data, systematic retrospective studies can be a useful foundation for robust and large-scale prospective studies to emerge. Given the lack of systematic data on the course of bipolar disorder in this setting, we planned to characterize the course of this disorder among patients attending a tertiary care center using a widely accepted retrospective life chart method in this cross-sectional study. We also attempted to assess the influence of gender and substance use disorder comorbidity on the course of the illness; as well as the recurrence rates after a first episode.
2. Methods 2.1. Setting of the study The study was conducted at the Department of Psychiatry of a tertiary-care government teaching hospital located in a semi-urban area of southern India. The center has both outpatient and inpatient facilities, and caters to patients with a wide variety of psychiatric disorders. Most patients belong to lower socio-economic status and treatment is provided at a substantial subsidy. Patients seeking care at the hospital are either self-referred, or are referred from other hospitals or private practitioners. They are usually accompanied by their family members. At the time of initial registration, patients are evaluated by trained psychiatrists and treatment is instituted. The patients are then evaluated in detail at the earliest possible date by residents and the diagnosis is verified by consultants as per ICD-10 clinical descriptions and diagnostic guidelines (CDDG). A management plan is formulated and treatment is provided in the form of pharmacotherapy and/or psychosocial intervention. There is a separate mood disorder follow-up clinic run once a week in the outpatient department. The hospital has a stable cohort of patients who have been receiving care for many years. 2.2. Sample characteristics This cross-sectional observational study was conducted among a single group of patients with bipolar I disorder. Non-probabilistic sampling was used to recruit study subjects. Both patients on longterm follow-up and those recently admitted as in-patients with a diagnosis of bipolar disorder were screened for participation. The inclusion criteria were: age 18–60 years; diagnosis of bipolar I disorder using the Structured Clinical Interview for Axis-I disorders for DSM-IV TR (SCID-I); patient accompanied by a key informant; and duration of illness of at least 3 years. For the purpose of the study, a key informant was defined as a person who lives with the patient and has known him/her long enough to have witnessed a considerable period of the illness. Patients who were currently violent and uncooperative, or had any neurological disorder as per clinical history and physical examination were excluded. Those fulfilling the inclusion and exclusion criteria were recruited after obtaining signed informed consent. The target sample for the present study was kept at 150 to ensure comparability to previous studies and also in view of feasibility of recruitment at the center. 2.3. Procedure of the study Patients who were included in the study were evaluated by the first author (KS). Information was gathered in one or two sittings from the patients, the key informant, and case records. A semistructured proforma was used to assess demographic and clinical characteristics. Substance use disorders were assessed using SCID-I.
Information about the course of bipolar illness was gathered using the National Institute of Mental Health- Life Chart Methodology Clinician Retrospective Chart (henceforth referred to as NIMH-LCM). Current mood symptoms were assessed using the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS). Patient recruitment was completed in the period between September 2012 and July 2014. The study was approved by the Institute Ethics Committee. 2.4. Instruments The NIMH-LCM was used for charting the course of illness for each patient. This clinician-rated scale charts the phases of the illness for the entirety of a patient's life. Charting may start with the first/index episode mentioning its polarity, and progresses along each episode. This method allows specification of the type of episode, its duration and severity. It also allows the coding of comorbid symptoms, triggering life events, hospitalization, medication use and other relevant details. The instrument has shown robust performance in ascertainment of retrospective information from patients (Roy-Byrne et al., 1985). The YMRS is an 11-item clinician rated instrument used for assessing manic symptoms (Young et al., 1978). The total scores of this scale can range from 0 to 60, with scores of 7 or below denoting remission. The scale has shown good inter-rater reliability and the scores have been demonstrated to correlate well with patient progress. The HDRS is a 17 item clinician rated instrument used for evaluation of symptoms of depression (Hamilton, 1960). A cut-off score of 8 is generally used to ascertain remission from depression. This scale has been widely used for assessment of depressive symptoms. 2.5. Statistical analysis Statistical analysis was carried out using SPSS version 17. Information was extracted from the NIMH-LCM of each individual patient regarding the duration of illness and the number of episodes. The number and duration of each episode in the life chart (mania, depression, hypomania and mixed affective state) were entered separately. The time spent in each type of episode (in months) was calculated for each patient. The total duration in episodes was divided by the duration of illness to compute the proportion of time spent in illness. The type of index (first) episode that was encountered was derived from the life chart to assess the relative frequencies of the first episodes. Thereafter, survival analysis was conducted to assess the time to relapse from the index episode. Cox-proportional hazards were used to find the independent predictors of time to relapse. A p value of less than 0.05 was considered significant for all the analyses.
3. Results 3.1. Demographic and clinical characteristics A total of 150 patients were recruited in the study (Fig. 1) out of 492 screened patients. The characteristics of the patients are depicted in Table 1. About half of the participants were males (48.0%) and were educated below high school (60.6%). The majority of the participants were from a lower socio-economic background (92.0%). The mean age at onset of bipolar I disorder was 24.8 years (78.2 years). In our study, 26% of the sample (n ¼39) had substance abuse or dependence. Alcohol use disorder was found in 20% (n ¼30) and nicotine in 17% (n ¼26). Only one person had cannabis use disorder.
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Table 2 Course characteristics of the total sample [n ¼150].
Screened for the study (n=492)
Excluded from the study (n=342) • BP but duration < three yrs=172 • Not BP-I diagnosis (schizoaffective, Bipolar
• • • •
NOS, BP-II, Mood disorder due to GMC/Substance Induced)=71 No key informant=35 Not met Age criteria >60 yrs =18 Mental retardation =14 Others (could not keep appointment /incomplete information/ case record not available/ uncooperative) =32
Mean (SD)
Median (Range)
Overall characteristics Age at onset (in years) Total duration of illness (in years) Number of episodes Time spent in episodes (in months) Percentage of time spent in illness phase
24.8(8.2) 13.4(8.3) 5.7(5.4) 13.6(9.0) 11.1(8.0)
23.0(12.2–52.1) 12(3–42) 5(2–60) 12(3–60) 8.3(1.3–41.7)
Duration of individual episodes (in months) Depression Mania Hypomania Mixed
2.26(1.59) 2.49(1.48) 1.39(0.33) 2.45(1.31)
2(0.5–13) 2(0.5–12) 1.5(1–2) 2.5(1–5)
Included in the study Percentage of time spent in different phases
(n=150) Fig. 1. Sample recruitment.
Mania, 9.26% Table 1 Socio-demographic and clinical characteristic of the sample (N ¼ 150). Variable
N (percentage) or mean (standard deviation)
Age Gender Male Female Education Illiterate Primary High school High secondary Graduate Post graduate Occupation
37.8(9.8)
Not working Working Religion Hindu Christian Muslim Socio-economic status Lower Middle Higher Age at illness onset (in years) YMRS score at assessment HDRS-17 item score at assessment Substance use Nicotine Alcohol Cannabis Any substance use Family history Mood disorder Substance use disorder Any mental disorder
72(48.0%) 78(52.0%) 11(7.3%) 65(43.3%) 28(18.7%) 20(13.4%) 21(14.0%) 5(3.3%) 70(46.7%) 80(53.3%) 133(88.6%) 10(6.7%) 7(4.7%) 138(92.0%) 11(7.3%) 1(0.7%) 24.8(8.2) 3.7(5.2) 1.8(2.4) 26(17.3%) 30(20.0%) 1(0.7%) 39(26.0%) 18(12.0%) 32(21.3%) 59(39.3%)
HDRS Hamilton Depression Rating Scale, SD Standard Deviation, YMRS Young Mania Rating Scale.
3.2. Course of bipolar disorder The course characteristics are summarized in Table 2. On an average the subjects had around 5.7 mood episodes during their entire duration of total illness period of about 13.4 years. On an average for the overall sample, an individual suffered 4.59 (75.38) manic episodes, 0.95 ( 71.54) depressive episodes, 0.08 (70.32) mixed episodes and 0.06 (70.52) hypomanic episodes. Seventynine patients (52.7% of the sample) had only recurrent manic
Not in syndomal episode, 88.91%
In episode, 11.11%
Depression, 1.64% Hypomania, 0.05 %
Mixed state, 0.16%
Fig. 2. Percentage time spent in various phases of Bipolar I disorder in the total duration of illness for the entire study population (N ¼ 150).
episodes (unipolar mania). Depressive, mixed and hypomanic episodes were noted in 63, 11 and 3 patients respectively (comprising 42.0%, 7.3% and 2.0% of the sample respectively). The time spent in each type of episode was calculated and expressed as the percentage of the time spent in the illness phase (Fig. 2). On an average, study subjects spent only 11.1% of their total illness period in the syndromal phases of the illness, bulk of which comprised of manic episodes. Time spent in mania was the maximum followed by depressive episode, mixed episode and hypomania. 3.3. Effect of gender and substance use on course characteristics The influence of gender and substance use on course characteristics is shown in Table 3. It was seen that women spent a higher percentage of time in the illness phase compared to men (12.5% versus 9.5%, p¼0.045). There were no significant differences in other course characteristics such as age of onset, duration of illness, and number of episodes across the two genders. Patients with substance use did not differ significantly from non-users in their course characteristics. 3.4. Index episode and recurrence after index episode The first (index) episode was mania in 127 patients, depression in 22 patients and mixed in 1 patient. Of the 63 patients with a lifetime depressive episode, the first episode was depression in only 22 (34.9% of those having at least one depressive episode), and was mania in the remaining 41 (65.1%). The time to recurrence after index episode is shown in Fig. 3A. After the first episode of illness, median time to recurrence (of any polarity) was 21 months (IQR: 10–60 months). For an index episode of mania (n¼ 127 patients), the median time to recurrence was 24 months (IQR: 10–60 months). Depression as the first episode (n¼22 patients) had a median time to recurrence of 19 months (IQR: 2–65 months). The only patient with a mixed affective state as the first episode relapsed after 36.5 months. The time to recurrence after a
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Table 3 Influence of gender and substance use status on course. A. Gender and course
Male (n¼ 72) Mean (SD)
Female (n¼ 78) Mean (SD)
Comparison: Mann Whitney U value (p Value)
Age at onset (in years) Total duration of illness (in years) Number of episodes Time spent in episodes (in months) Percentage of time spent in illness phase
24.9 14.5 6.1 13.6 9.5
24.7 (8.8) 12.3 (8.0) 5.3 (3.2) 13.6 (8.5) 12.5 (9.0)
2638.5 2333 2791 2706 2275.5
B. Substance use and course
Without substance use disorder (n¼111) Mean (SD)
With substance use disorder (n¼ 39) Mean (SD)
Age at onset (in years) Total duration of illness (in years) Number of episodes Time spent in episodes (in months) Percentage of time spent in illness phase
24.3 (7.9) 12.9 (7.9) 5.4 (3.1) 13.8 (8.3) 11.7 (8.3)
26.1 (9.2) 14.9 (9.3) 6.6 (9.3) 13.3 (10.7) 9.4 (6.4)
(7.7) (8.5) (7.1) (9.5) (6.4)
(0.524) (0.074) (0.949) (0.701) (0.045)n
1991 (0.457) 1912 (0.279) 2053.5 (0.631) 1899.5 (0.255) 1780.5 (0.100)
NIMH – LCM CRC National Institute of Mental Health- Life Chart Methodology Clinician Retrospective Chart, SD standard deviation. n
po 0.05.
first episode was significantly earlier for women when compared to men (median time to recurrence: 20 months versus 34 months, Mantel–Cox Log Rank¼ 6.577, p¼0.010). Cox's proportional hazards were computed to look for predictors of time to recurrence. Age at onset, gender, polarity of the first episode, presence of comorbid substance use disorder, education status and socio-occupational status were included into the analysis, as these variables would have been available at the first episode. The model revealed that gender was the only independent predictor of recurrence. Female gender was associated with a 33.9% shorter time to relapse than men (95% confidence interval of 8.3–52.4%).
4. Discussion
Fig. 3. Survival curves with time to recurrence after the first episode. A. Time to recurrence across polarity of index episode. B. Time to recurrence across gender.
The present study using a standardized life chart methodology found that the first episode in our sample was mania in an overwhelming majority of cases, which is similar to findings from other studies in the region (Chopra et al., 2006; Khanna et al., 1992) including a recent study in which 72% had an index episode of mania (Chopra et al., 2006). This is in contrast to studies from Europe, where index depression is more frequent. For example, only 41% had manic onset in Denmark (Backlund et al., 2009); 67% had a depressive onset in a Spanish sample (Daban et al., 2006) and 50% had depressive onset in an Italian sample (Perugi et al., 2000). Over the course of the illness, mania was more common than other types of episodes, which is in concurrence with the literature from both India (Chopra et al., 2006; Khanna et al., 1992). and other tropical areas such as Nigeria (Makanjuola, 1985). These differences have been reviewed and hypothesized by Narayanaswamy et al., 2014 to be due to the effect of latitude as a zeitgeber in bipolar disorder. In contrast, data from the temperate regions (Judd et al., 2002; Perugi et al., 2000) points to a greater time spent in the depressive phase. The ratio of time spent in depressed and manic phases was the reverse of what was observed in studies from Europe and USA (Judd et al., 2003), where patients may spend three times as many days in depression as in mania (Kupka et al., 2007), reflecting again the predominance of manic episodes in the present sample. The predominant polarity has management implications, and the concept of polarity index has been suggested in this regard which is the ratio of number needed to treat (NNT) for depression prevention to the NNT for mania prevention (Popovic et al., 2012). Knowledge of predominant polarity and polarity index can be utilized as a guide for
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determining the choice of treatment, as different pharmacological and non-pharmacological measures vary in their relative efficacies for mania and depression prevention (Popovic et al., 2012; 2013). The predominance of manic polarity of bipolar I disorder in the present study matches with the findings from other tropical countries and is contrary to findings from temperate countries. There are various possible reasons for this difference. Firstly, it may reflect actual differences in the occurrence of the type of episodes in different regions of the world. The zeitgeber effect has been proposed as an explanation for the increase in manic polarity of bipolar illness as we move towards lower equatorial latitudes (Narayanaswamy et al., 2014). Secondly, such a finding may also arise due to proclivity of the patients and their family members towards recollecting disruptive manic episodes. Recollection of depressive episodes could have been missed by patients and family members due to the greater impact of manic episodes. However, since bipolar depression presents more frequently with serious manifestations like psychomotor retardation and psychotic symptoms (Mitchell et al., 2011), it unlikely that failure of recall of depressive episodes would be considerable. Thirdly, the differences in polarity of episodes might be accounted for by possible gene–environment interactions. The mean age at onset of illness among our patients was 24.8 years (SD ¼8.2). This is similar to previous study from the same region by Chopra et al. (2006) and studies by Judd et al. (2002) and Backlund et al. (2009). Yatham et al. (2009) found a mean age at onset of 19.3 years (SD ¼ 4.3) in a study comprising of patients with first episode mania, which is much younger than our sample. The mean length of the episodes in the present study suggested that manic and depressive episodes lasted on an average between 2 and 3 months. These durations are shorter than those reported in previous literature from elsewhere (Solomon et al., 2013; Wittchen et al., 2003). However, recent studies have shown that the mean episode duration is shorter than what has been historically described (Chopra et al., 2006; Judd et al., 2002). Since this hospital-based study included patients who were on follow-up, the shorter durations of episodes may also be reflect the effects of treatment and the role of the family in early identification and facilitation of treatment. The present study suggests that one-tenth of the illness duration was spent in the syndromal phase. There is evidence from the literature that subsyndromal mood states might be present in a substantial proportion of time during the illness course, and might be associated with functional impairment (Judd et al., 2003; Sala et al., 2009). The subsyndromal phase of the illness was not assessed in the present study due to obvious difficulties in reliable recall, and could be better assessed in prospective study designs. Female patients with bipolar disorder in the present sample spent significantly more time ill (12.5% versus 9.5%). This could be due to the health care and treatment access issues in the population, wherein women find it difficult to access to healthcare services compared to men, leading to delays in diagnosis and treatment (Arnold, 2003); alternately, it could reflect a genuine gender effect (Diflorio and Jones, 2010) or the influence of a confounding factor, such as subclinical thyroid dysfunction (Bauer et al., 2014). No significant differences were found in the other characteristics of onset and course of the illness, which is in line with other studies (Coryell et al., 2013; Judd et al., 2003). The rates of substance use disorder were lower compared to studies from the west (Grant et al., 2005), but are similar to those reported in the region (Munoli et al., 2014). The lower rates are partly accounted by the lower prevalence of substance use disorders in India (Reddy and Chandrashekar, 1998). The study did not find an association between substance use disorder and poor course characteristics, which is similar to another study (Lagerberg et al., 2010), but at a variance from the findings reported in other studies (Cassidy et al., 2001; van Rossum et al., 2009).
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The median time to recurrence after first episode was 21 months (inter-quartile range of 10–60 months). This time to recurrence is longer than is reported elsewhere in the West (Simhandl et al., 2014; Yatham et al., 2009). A prospective follow up study from Thailand has shown similar rates of relapse as in the present study (Leelahanaj et al., 2013). The reasons of low relapse rates could be possibly attributed to the involvement of family members in the treatment in Indian context. Patients most often live with other family members who help the patient with procurement of medication and provide supervision. Poor adherence is one of the major factors for relapse of bipolar disorder (Gutiérrez-Rojas et al., 2010), which is probably mitigated by active participation of family members in treatment process.
5. Limitations Some limitations of the present study should be considered while drawing inferences. NIMH-LCM as a study instrument has the possibility of recall bias affecting some of the study findings, as it was based upon retrospective recall. Collateral information was obtained from the key informants, as well as case records to minimize possibility of such errors. Still, the retrospective nature of the study limits the absolute confidence on the results. This study has used a predominantly clinic based population of BP-I patients only. This sample might be representative of patients following up at a general hospital psychiatry unit, but is not generalizable to a community sample. The lack of differences between those with and without substance use disorders could be due to the study being underpowered to detect differences in sub-group analyses. Finally, precipitating factors and longitudinal medication adherence were not assessed in this study.
6. Conclusion In conclusion, the present study suggests that the average age of onset in Indian patients with bipolar I disorder is about 25 years. Manic episodes are far more common than depressive ones, and about half of these patients experience only unipolar manic episodes. About one-tenth of the illness duration is spent in episodes of syndromal illness. About half the patients relapse within the first two years after the onset of illness, with the time to relapse being shorter in women. The finding of more frequent manic episodes in the present population provides a launching pad for future prospective studies looking at subsyndromal manic and depressive symptoms during follow up, and assessing their relationship with functioning. The findings also call for robust research on mood stabilizers and anti-manic agents, and devising service delivery methods for early recognition and control of symptoms in the present population to improve patient outcomes.
Role of funding source The present work was non-funded.
Conflict of interest The authors declare no conflicts of interest.
Acknowledgments None.
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Sagar, Z., Wells, J.E., Zarkov, Z., 2011. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch. Gen. Psychiatry 68, 241–251. http://dx.doi.org/10.1001/archgenpsychiatry.2011.12. Mitchell, P.B., Frankland, A., Hadzi-Pavlovic, D., Roberts, G., Corry, J., Wright, A., Loo, C.K., Breakspear, M., 2011. Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees. Br. J. Psychiatry J. Ment. Sci. 199, 303–309. http://dx.doi.org/10.1192/bjp.bp.110.088823. Munoli, R.N., Praharaj, S.K., Sharma, P.S.V.N., 2014. Co-morbidity in bipolar disorder: a retrospective study. Indian J. Psychol. Med. 36, 270–275. http://dx.doi.org/ 10.4103/0253-7176.135377. Narayanaswamy, J.C., Moily, N., Kubendran, S., Janardhan Reddy, Y.C., Jain, S., 2014. Does latitude as a zeitgeber affect the course of bipolar affective disorder? Med. Hypotheses. http://dx.doi.org/10.1016/j.mehy.2014.06.017. Perugi, G., Micheli, C., Akiskal, H.S., Madaro, D., Socci, C., Quilici, C., Musetti, L., 2000. Polarity of the first episode, clinical characteristics, and course of manic depressive illness: a systematic retrospective investigation of 320 bipolar I patients. Compr. Psychiatry 41, 13–18. Popovic, D., Reinares, M., Goikolea, J.M., Bonnin, C.M., Gonzalez-Pinto, A., Vieta, E., 2012. Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Eur. Neuropsychopharmacol. 22, 339–346. http://dx.doi. org/10.1016/j.euroneuro.2011.09.008. Popovic, D., Reinares, M., Scott, J., Nivoli, A., Murru, A., Pacchiarotti, I., Vieta, E., Colom, F., 2013. Polarity index of psychological interventions in maintenance treatment of bipolar disorder. Psychother. Psychosom. 82, 292–298. http://dx. doi.org/10.1159/000348447. Reddy, V.M., Chandrashekar, C.R., 1998. Prevalence of mental and behavioural disorders in India: a meta-analysis. Indian J. Psychiatry 40, 149–157. Roy-Byrne, P., Post, R.M., Uhde, T.W., Porcu, T., Davis, D., 1985. The longitudinal course of recurrent affective illness: life chart data from research patients at the NIMH. Acta Psychiatr. Scand. Suppl. 317, 1–34. Sala, R., Axelson, D., Birmaher, B., 2009. Phenomenology, longitudinal course, and outcome of children and adolescents with bipolar spectrum disorders (vii). Child Adolesc. Psychiatr. Clin. N. Am. 18, 273–289. http://dx.doi.org/10.1016/j. chc.2008.11.002. Simhandl, C., König, B., Amann, B.L., 2014. A prospective 4-year naturalistic followup of treatment and outcome of 300 bipolar I and II patients (quiz 263). J. Clin. Psychiatry 75, 254–262. http://dx.doi.org/10.4088/JCP.13m08601. Smith, L.A., Cornelius, V., Warnock, A., Bell, A., Young, A.H., 2007. Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disord. 9, 394–412. http://dx.doi.org/10.1111/j.1399-5618.2007.00490.x. Solomon, D.A., Fiedorowicz, J.G., Leon, A.C., Coryell, W., Endicott, J., Li, C., Boland, R.J., Keller, M.B., 2013. Recovery from multiple episodes of bipolar I depression. J. Clin. Psychiatry 74, e205–e211. http://dx.doi.org/10.4088/JCP.12m08049. van Rossum, I., Boomsma, M., Tenback, D., Reed, C., van Os, J., EMBLEM Advisory Board, 2009. Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis. J. Nerv. Ment. Dis. 197, 35–40. http://dx.doi.org/10.1097/ NMD.0b013e31819292a6. Wittchen, H.U., Mhlig, S., Pezawas, L., 2003. Natural course and burden of bipolar disorders. Int. J. Neuropsychopharmacol. 6, 145–154. http://dx.doi.org/10.1017/ S146114570300333X. Yatham, L.N., Kauer-Sant'Anna, M., Bond, D.J., Lam, R.W., Torres, I., 2009. Course and outcome after the first manic episode in patients with bipolar disorder: prospective 12-month data from the Systematic Treatment Optimization Program for Early Mania project. Can. J. Psychiatry 54, 105–112. Yatham, L.N., Kennedy, S.H., Parikh, S.V., Schaffer, A., Beaulieu, S., Alda, M., O'Donovan, C., Macqueen, G., McIntyre, R.S., Sharma, V., Ravindran, A., Young, L.T., Milev, R., Bond, D.J., Frey, B.N., Goldstein, B.I., Lafer, B., Birmaher, B., Ha, K., Nolen, W.A., Berk, M., 2013. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 15, 1–44. http://dx.doi.org/10.1111/bdi.12025. Young, R.C., Biggs, J.T., Ziegler, V.E., Meyer, D.A., 1978. A rating scale for mania: reliability, validity and sensitivity. Br. J. Psychiatry 133, 429–435.
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Research report
Long term course of bipolar I disorder in India: Using retrospective life chart method Subramanian Karthick, Shivanand Kattimani n, Ravi Philip Rajkumar, Balaji Bharadwaj, Siddharth Sarkar Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
art ic l e i nf o
a b s t r a c t
Article history: Received 12 September 2014 Received in revised form 30 October 2014 Accepted 31 October 2014 Available online 13 November 2014
Background: There are grounds to believe that the course of bipolar disorder may be different in tropical countries such as India when compared to temperate nations. There is a dearth of literature about the course of bipolar I disorder from India. Methods: This study was conducted in a multispecialty teaching hospital in southern India. Patients with a DSM-IV TR diagnosis of bipolar I disorder, confirmed using SCID-I, with a minimum duration of illness of 3 years were assessed. Information was gathered on demographic and clinical variables, and the life course of episodes was charted using the National Institute of Mental Health – Life Chart Methodology Clinician Retrospective Chart (NIMH-LCM-CRC). Results: A total of 150 patients with bipolar disorder were included. The mean age at onset of illness was 24.8 ( 78.2) years. Mania was the first episode in a majority (85%) of the cases, and was the most frequent episode in the course of the illness, followed by depression. Patients spent an average of 11.1% of the illness duration in a mood episode, most commonly a manic episode. The median duration of manic or depressive episode was 2 months. Median time to recurrence after the first episode was 21 months (inter-quartile range of 10–60 months), and was shorter for women than men. Limitations: The hospital based sample from a particular region limits generalizability. Recall bias may be present in this retrospective information based study. Medical illness, personality disorders, other Axis I psychiatric disorders (apart from substance use disorder) and influence of adherence to treatment on the course of the disorder were not assessed systematically. Conclusions: Bipolar I disorder among Indian patients has a course characterized by predominantly manic episodes, which is in line with previous reports from tropical countries and substantially different from that of temperate regions. & 2014 Elsevier B.V. All rights reserved.
Keywords: Bipolar disorder Follow-up studies Prognosis Psychiatric status rating scales Gender India
1. Introduction Bipolar disorder is a severe chronic psychiatric disorder associated with considerable morbidity (Gitlin et al., 1995; Goldberg and Harrow, 2005). The course of this disorder is characterized by recurrent relapses, the frequency of which can be reduced with the help of effective medications (Grandjean and Aubry, 2009; Smith et al., 2007). A wide variation exists among individuals with bipolar disorder in terms of the course of illness. Characterizing the course of bipolar disorder can be helpful in understanding the impact of this illness on the patient and society. Such characterization is also helpful when planning therapeutic and service modalities for patients with this disorder (Yatham et al., 2013).
n
Corresponding author. E-mail address: [email protected] (S. Kattimani).
http://dx.doi.org/10.1016/j.jad.2014.10.056 0165-0327/& 2014 Elsevier B.V. All rights reserved.
The recently conducted World Mental Health survey found that the prevalence of bipolar spectrum disorder is 0.1% in India (Merikangas et al., 2011), of which bipolar I disorder accounts for approximately 20%. This estimate translates to a patient load of about 0.2 million individuals with bipolar I disorder. It has recently been suggested that the course of bipolar disorder may be different in tropical countries like India with a preponderance of manic episodes (Narayanaswamy et al., 2014), as compared to the temperate developed nations from where the majority of the published literature on bipolar disorder has emerged. If such differences in the types of episodes exist, they would have contextual implications in the management and service delivery focus of this vast patient population. There is a paucity of research about the course of bipolar disorder in tropical countries including India. Though studies in the west have progressed from chart based studies to long term cohorts including assessment of weekly mood state by 6 monthly retrospective recalls (Judd et al., 2003, 2002), there is a lack of
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longer term studies of the course and outcome of adults with bipolar disorder from India, and sample sizes in these studies have generally been small (Chopra et al., 2006; Khanna et al., 1992; Khess et al., 1997). In the absence of prospective data, systematic retrospective studies can be a useful foundation for robust and large-scale prospective studies to emerge. Given the lack of systematic data on the course of bipolar disorder in this setting, we planned to characterize the course of this disorder among patients attending a tertiary care center using a widely accepted retrospective life chart method in this cross-sectional study. We also attempted to assess the influence of gender and substance use disorder comorbidity on the course of the illness; as well as the recurrence rates after a first episode.
2. Methods 2.1. Setting of the study The study was conducted at the Department of Psychiatry of a tertiary-care government teaching hospital located in a semi-urban area of southern India. The center has both outpatient and inpatient facilities, and caters to patients with a wide variety of psychiatric disorders. Most patients belong to lower socio-economic status and treatment is provided at a substantial subsidy. Patients seeking care at the hospital are either self-referred, or are referred from other hospitals or private practitioners. They are usually accompanied by their family members. At the time of initial registration, patients are evaluated by trained psychiatrists and treatment is instituted. The patients are then evaluated in detail at the earliest possible date by residents and the diagnosis is verified by consultants as per ICD-10 clinical descriptions and diagnostic guidelines (CDDG). A management plan is formulated and treatment is provided in the form of pharmacotherapy and/or psychosocial intervention. There is a separate mood disorder follow-up clinic run once a week in the outpatient department. The hospital has a stable cohort of patients who have been receiving care for many years. 2.2. Sample characteristics This cross-sectional observational study was conducted among a single group of patients with bipolar I disorder. Non-probabilistic sampling was used to recruit study subjects. Both patients on longterm follow-up and those recently admitted as in-patients with a diagnosis of bipolar disorder were screened for participation. The inclusion criteria were: age 18–60 years; diagnosis of bipolar I disorder using the Structured Clinical Interview for Axis-I disorders for DSM-IV TR (SCID-I); patient accompanied by a key informant; and duration of illness of at least 3 years. For the purpose of the study, a key informant was defined as a person who lives with the patient and has known him/her long enough to have witnessed a considerable period of the illness. Patients who were currently violent and uncooperative, or had any neurological disorder as per clinical history and physical examination were excluded. Those fulfilling the inclusion and exclusion criteria were recruited after obtaining signed informed consent. The target sample for the present study was kept at 150 to ensure comparability to previous studies and also in view of feasibility of recruitment at the center. 2.3. Procedure of the study Patients who were included in the study were evaluated by the first author (KS). Information was gathered in one or two sittings from the patients, the key informant, and case records. A semistructured proforma was used to assess demographic and clinical characteristics. Substance use disorders were assessed using SCID-I.
Information about the course of bipolar illness was gathered using the National Institute of Mental Health- Life Chart Methodology Clinician Retrospective Chart (henceforth referred to as NIMH-LCM). Current mood symptoms were assessed using the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS). Patient recruitment was completed in the period between September 2012 and July 2014. The study was approved by the Institute Ethics Committee. 2.4. Instruments The NIMH-LCM was used for charting the course of illness for each patient. This clinician-rated scale charts the phases of the illness for the entirety of a patient's life. Charting may start with the first/index episode mentioning its polarity, and progresses along each episode. This method allows specification of the type of episode, its duration and severity. It also allows the coding of comorbid symptoms, triggering life events, hospitalization, medication use and other relevant details. The instrument has shown robust performance in ascertainment of retrospective information from patients (Roy-Byrne et al., 1985). The YMRS is an 11-item clinician rated instrument used for assessing manic symptoms (Young et al., 1978). The total scores of this scale can range from 0 to 60, with scores of 7 or below denoting remission. The scale has shown good inter-rater reliability and the scores have been demonstrated to correlate well with patient progress. The HDRS is a 17 item clinician rated instrument used for evaluation of symptoms of depression (Hamilton, 1960). A cut-off score of 8 is generally used to ascertain remission from depression. This scale has been widely used for assessment of depressive symptoms. 2.5. Statistical analysis Statistical analysis was carried out using SPSS version 17. Information was extracted from the NIMH-LCM of each individual patient regarding the duration of illness and the number of episodes. The number and duration of each episode in the life chart (mania, depression, hypomania and mixed affective state) were entered separately. The time spent in each type of episode (in months) was calculated for each patient. The total duration in episodes was divided by the duration of illness to compute the proportion of time spent in illness. The type of index (first) episode that was encountered was derived from the life chart to assess the relative frequencies of the first episodes. Thereafter, survival analysis was conducted to assess the time to relapse from the index episode. Cox-proportional hazards were used to find the independent predictors of time to relapse. A p value of less than 0.05 was considered significant for all the analyses.
3. Results 3.1. Demographic and clinical characteristics A total of 150 patients were recruited in the study (Fig. 1) out of 492 screened patients. The characteristics of the patients are depicted in Table 1. About half of the participants were males (48.0%) and were educated below high school (60.6%). The majority of the participants were from a lower socio-economic background (92.0%). The mean age at onset of bipolar I disorder was 24.8 years (78.2 years). In our study, 26% of the sample (n ¼39) had substance abuse or dependence. Alcohol use disorder was found in 20% (n ¼30) and nicotine in 17% (n ¼26). Only one person had cannabis use disorder.
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257
Table 2 Course characteristics of the total sample [n ¼150].
Screened for the study (n=492)
Excluded from the study (n=342) • BP but duration < three yrs=172 • Not BP-I diagnosis (schizoaffective, Bipolar
• • • •
NOS, BP-II, Mood disorder due to GMC/Substance Induced)=71 No key informant=35 Not met Age criteria >60 yrs =18 Mental retardation =14 Others (could not keep appointment /incomplete information/ case record not available/ uncooperative) =32
Mean (SD)
Median (Range)
Overall characteristics Age at onset (in years) Total duration of illness (in years) Number of episodes Time spent in episodes (in months) Percentage of time spent in illness phase
24.8(8.2) 13.4(8.3) 5.7(5.4) 13.6(9.0) 11.1(8.0)
23.0(12.2–52.1) 12(3–42) 5(2–60) 12(3–60) 8.3(1.3–41.7)
Duration of individual episodes (in months) Depression Mania Hypomania Mixed
2.26(1.59) 2.49(1.48) 1.39(0.33) 2.45(1.31)
2(0.5–13) 2(0.5–12) 1.5(1–2) 2.5(1–5)
Included in the study Percentage of time spent in different phases
(n=150) Fig. 1. Sample recruitment.
Mania, 9.26% Table 1 Socio-demographic and clinical characteristic of the sample (N ¼ 150). Variable
N (percentage) or mean (standard deviation)
Age Gender Male Female Education Illiterate Primary High school High secondary Graduate Post graduate Occupation
37.8(9.8)
Not working Working Religion Hindu Christian Muslim Socio-economic status Lower Middle Higher Age at illness onset (in years) YMRS score at assessment HDRS-17 item score at assessment Substance use Nicotine Alcohol Cannabis Any substance use Family history Mood disorder Substance use disorder Any mental disorder
72(48.0%) 78(52.0%) 11(7.3%) 65(43.3%) 28(18.7%) 20(13.4%) 21(14.0%) 5(3.3%) 70(46.7%) 80(53.3%) 133(88.6%) 10(6.7%) 7(4.7%) 138(92.0%) 11(7.3%) 1(0.7%) 24.8(8.2) 3.7(5.2) 1.8(2.4) 26(17.3%) 30(20.0%) 1(0.7%) 39(26.0%) 18(12.0%) 32(21.3%) 59(39.3%)
HDRS Hamilton Depression Rating Scale, SD Standard Deviation, YMRS Young Mania Rating Scale.
3.2. Course of bipolar disorder The course characteristics are summarized in Table 2. On an average the subjects had around 5.7 mood episodes during their entire duration of total illness period of about 13.4 years. On an average for the overall sample, an individual suffered 4.59 (75.38) manic episodes, 0.95 ( 71.54) depressive episodes, 0.08 (70.32) mixed episodes and 0.06 (70.52) hypomanic episodes. Seventynine patients (52.7% of the sample) had only recurrent manic
Not in syndomal episode, 88.91%
In episode, 11.11%
Depression, 1.64% Hypomania, 0.05 %
Mixed state, 0.16%
Fig. 2. Percentage time spent in various phases of Bipolar I disorder in the total duration of illness for the entire study population (N ¼ 150).
episodes (unipolar mania). Depressive, mixed and hypomanic episodes were noted in 63, 11 and 3 patients respectively (comprising 42.0%, 7.3% and 2.0% of the sample respectively). The time spent in each type of episode was calculated and expressed as the percentage of the time spent in the illness phase (Fig. 2). On an average, study subjects spent only 11.1% of their total illness period in the syndromal phases of the illness, bulk of which comprised of manic episodes. Time spent in mania was the maximum followed by depressive episode, mixed episode and hypomania. 3.3. Effect of gender and substance use on course characteristics The influence of gender and substance use on course characteristics is shown in Table 3. It was seen that women spent a higher percentage of time in the illness phase compared to men (12.5% versus 9.5%, p¼0.045). There were no significant differences in other course characteristics such as age of onset, duration of illness, and number of episodes across the two genders. Patients with substance use did not differ significantly from non-users in their course characteristics. 3.4. Index episode and recurrence after index episode The first (index) episode was mania in 127 patients, depression in 22 patients and mixed in 1 patient. Of the 63 patients with a lifetime depressive episode, the first episode was depression in only 22 (34.9% of those having at least one depressive episode), and was mania in the remaining 41 (65.1%). The time to recurrence after index episode is shown in Fig. 3A. After the first episode of illness, median time to recurrence (of any polarity) was 21 months (IQR: 10–60 months). For an index episode of mania (n¼ 127 patients), the median time to recurrence was 24 months (IQR: 10–60 months). Depression as the first episode (n¼22 patients) had a median time to recurrence of 19 months (IQR: 2–65 months). The only patient with a mixed affective state as the first episode relapsed after 36.5 months. The time to recurrence after a
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Table 3 Influence of gender and substance use status on course. A. Gender and course
Male (n¼ 72) Mean (SD)
Female (n¼ 78) Mean (SD)
Comparison: Mann Whitney U value (p Value)
Age at onset (in years) Total duration of illness (in years) Number of episodes Time spent in episodes (in months) Percentage of time spent in illness phase
24.9 14.5 6.1 13.6 9.5
24.7 (8.8) 12.3 (8.0) 5.3 (3.2) 13.6 (8.5) 12.5 (9.0)
2638.5 2333 2791 2706 2275.5
B. Substance use and course
Without substance use disorder (n¼111) Mean (SD)
With substance use disorder (n¼ 39) Mean (SD)
Age at onset (in years) Total duration of illness (in years) Number of episodes Time spent in episodes (in months) Percentage of time spent in illness phase
24.3 (7.9) 12.9 (7.9) 5.4 (3.1) 13.8 (8.3) 11.7 (8.3)
26.1 (9.2) 14.9 (9.3) 6.6 (9.3) 13.3 (10.7) 9.4 (6.4)
(7.7) (8.5) (7.1) (9.5) (6.4)
(0.524) (0.074) (0.949) (0.701) (0.045)n
1991 (0.457) 1912 (0.279) 2053.5 (0.631) 1899.5 (0.255) 1780.5 (0.100)
NIMH – LCM CRC National Institute of Mental Health- Life Chart Methodology Clinician Retrospective Chart, SD standard deviation. n
po 0.05.
first episode was significantly earlier for women when compared to men (median time to recurrence: 20 months versus 34 months, Mantel–Cox Log Rank¼ 6.577, p¼0.010). Cox's proportional hazards were computed to look for predictors of time to recurrence. Age at onset, gender, polarity of the first episode, presence of comorbid substance use disorder, education status and socio-occupational status were included into the analysis, as these variables would have been available at the first episode. The model revealed that gender was the only independent predictor of recurrence. Female gender was associated with a 33.9% shorter time to relapse than men (95% confidence interval of 8.3–52.4%).
4. Discussion
Fig. 3. Survival curves with time to recurrence after the first episode. A. Time to recurrence across polarity of index episode. B. Time to recurrence across gender.
The present study using a standardized life chart methodology found that the first episode in our sample was mania in an overwhelming majority of cases, which is similar to findings from other studies in the region (Chopra et al., 2006; Khanna et al., 1992) including a recent study in which 72% had an index episode of mania (Chopra et al., 2006). This is in contrast to studies from Europe, where index depression is more frequent. For example, only 41% had manic onset in Denmark (Backlund et al., 2009); 67% had a depressive onset in a Spanish sample (Daban et al., 2006) and 50% had depressive onset in an Italian sample (Perugi et al., 2000). Over the course of the illness, mania was more common than other types of episodes, which is in concurrence with the literature from both India (Chopra et al., 2006; Khanna et al., 1992). and other tropical areas such as Nigeria (Makanjuola, 1985). These differences have been reviewed and hypothesized by Narayanaswamy et al., 2014 to be due to the effect of latitude as a zeitgeber in bipolar disorder. In contrast, data from the temperate regions (Judd et al., 2002; Perugi et al., 2000) points to a greater time spent in the depressive phase. The ratio of time spent in depressed and manic phases was the reverse of what was observed in studies from Europe and USA (Judd et al., 2003), where patients may spend three times as many days in depression as in mania (Kupka et al., 2007), reflecting again the predominance of manic episodes in the present sample. The predominant polarity has management implications, and the concept of polarity index has been suggested in this regard which is the ratio of number needed to treat (NNT) for depression prevention to the NNT for mania prevention (Popovic et al., 2012). Knowledge of predominant polarity and polarity index can be utilized as a guide for
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determining the choice of treatment, as different pharmacological and non-pharmacological measures vary in their relative efficacies for mania and depression prevention (Popovic et al., 2012; 2013). The predominance of manic polarity of bipolar I disorder in the present study matches with the findings from other tropical countries and is contrary to findings from temperate countries. There are various possible reasons for this difference. Firstly, it may reflect actual differences in the occurrence of the type of episodes in different regions of the world. The zeitgeber effect has been proposed as an explanation for the increase in manic polarity of bipolar illness as we move towards lower equatorial latitudes (Narayanaswamy et al., 2014). Secondly, such a finding may also arise due to proclivity of the patients and their family members towards recollecting disruptive manic episodes. Recollection of depressive episodes could have been missed by patients and family members due to the greater impact of manic episodes. However, since bipolar depression presents more frequently with serious manifestations like psychomotor retardation and psychotic symptoms (Mitchell et al., 2011), it unlikely that failure of recall of depressive episodes would be considerable. Thirdly, the differences in polarity of episodes might be accounted for by possible gene–environment interactions. The mean age at onset of illness among our patients was 24.8 years (SD ¼8.2). This is similar to previous study from the same region by Chopra et al. (2006) and studies by Judd et al. (2002) and Backlund et al. (2009). Yatham et al. (2009) found a mean age at onset of 19.3 years (SD ¼ 4.3) in a study comprising of patients with first episode mania, which is much younger than our sample. The mean length of the episodes in the present study suggested that manic and depressive episodes lasted on an average between 2 and 3 months. These durations are shorter than those reported in previous literature from elsewhere (Solomon et al., 2013; Wittchen et al., 2003). However, recent studies have shown that the mean episode duration is shorter than what has been historically described (Chopra et al., 2006; Judd et al., 2002). Since this hospital-based study included patients who were on follow-up, the shorter durations of episodes may also be reflect the effects of treatment and the role of the family in early identification and facilitation of treatment. The present study suggests that one-tenth of the illness duration was spent in the syndromal phase. There is evidence from the literature that subsyndromal mood states might be present in a substantial proportion of time during the illness course, and might be associated with functional impairment (Judd et al., 2003; Sala et al., 2009). The subsyndromal phase of the illness was not assessed in the present study due to obvious difficulties in reliable recall, and could be better assessed in prospective study designs. Female patients with bipolar disorder in the present sample spent significantly more time ill (12.5% versus 9.5%). This could be due to the health care and treatment access issues in the population, wherein women find it difficult to access to healthcare services compared to men, leading to delays in diagnosis and treatment (Arnold, 2003); alternately, it could reflect a genuine gender effect (Diflorio and Jones, 2010) or the influence of a confounding factor, such as subclinical thyroid dysfunction (Bauer et al., 2014). No significant differences were found in the other characteristics of onset and course of the illness, which is in line with other studies (Coryell et al., 2013; Judd et al., 2003). The rates of substance use disorder were lower compared to studies from the west (Grant et al., 2005), but are similar to those reported in the region (Munoli et al., 2014). The lower rates are partly accounted by the lower prevalence of substance use disorders in India (Reddy and Chandrashekar, 1998). The study did not find an association between substance use disorder and poor course characteristics, which is similar to another study (Lagerberg et al., 2010), but at a variance from the findings reported in other studies (Cassidy et al., 2001; van Rossum et al., 2009).
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The median time to recurrence after first episode was 21 months (inter-quartile range of 10–60 months). This time to recurrence is longer than is reported elsewhere in the West (Simhandl et al., 2014; Yatham et al., 2009). A prospective follow up study from Thailand has shown similar rates of relapse as in the present study (Leelahanaj et al., 2013). The reasons of low relapse rates could be possibly attributed to the involvement of family members in the treatment in Indian context. Patients most often live with other family members who help the patient with procurement of medication and provide supervision. Poor adherence is one of the major factors for relapse of bipolar disorder (Gutiérrez-Rojas et al., 2010), which is probably mitigated by active participation of family members in treatment process.
5. Limitations Some limitations of the present study should be considered while drawing inferences. NIMH-LCM as a study instrument has the possibility of recall bias affecting some of the study findings, as it was based upon retrospective recall. Collateral information was obtained from the key informants, as well as case records to minimize possibility of such errors. Still, the retrospective nature of the study limits the absolute confidence on the results. This study has used a predominantly clinic based population of BP-I patients only. This sample might be representative of patients following up at a general hospital psychiatry unit, but is not generalizable to a community sample. The lack of differences between those with and without substance use disorders could be due to the study being underpowered to detect differences in sub-group analyses. Finally, precipitating factors and longitudinal medication adherence were not assessed in this study.
6. Conclusion In conclusion, the present study suggests that the average age of onset in Indian patients with bipolar I disorder is about 25 years. Manic episodes are far more common than depressive ones, and about half of these patients experience only unipolar manic episodes. About one-tenth of the illness duration is spent in episodes of syndromal illness. About half the patients relapse within the first two years after the onset of illness, with the time to relapse being shorter in women. The finding of more frequent manic episodes in the present population provides a launching pad for future prospective studies looking at subsyndromal manic and depressive symptoms during follow up, and assessing their relationship with functioning. The findings also call for robust research on mood stabilizers and anti-manic agents, and devising service delivery methods for early recognition and control of symptoms in the present population to improve patient outcomes.
Role of funding source The present work was non-funded.
Conflict of interest The authors declare no conflicts of interest.
Acknowledgments None.
References Arnold, L.M., 2003. Gender differences in bipolar disorder. Psychiatr. Clin. North Am. 26, 595–620.
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