Outcome of Bipolar I (mania) disorders, In Relation with Personality Profile

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1 APRIL 2008 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 Original Article Outcome of Bipolar I (mania) disorders, In Relation with Personality Profile L.N. Gupta, K.K. Verma, Shriniwas Department of Psychiatry, S.P. Medical College, Bikaner Abstract Objective: This prospective semi structured study evaluated the relations of symptomatology and outcome of bipolar manic patients with personality vulnerability. Methods: 52 patients of bipolar (mania) disorder, out of total 430 admitted patients in psychiatry ward, from January 10, to July 9, 2005 were included in the study. The patients with organic diseases or on any drugs for last two weeks were excluded from the study. All the patients were diagnosed as per ICD-10 diagnostic criteria. Patients of bipolar mania were administered Young Mania Rating Scale (YMRS) to assess the severity of mania. The personality traits and disorders were assessed by the help of ICD-10 module of International Personality Disorder Examination (IPDE). The stress in preceding one month was evaluated by using 41 items Presumptive Stressful Life Event Scale. Initial response to lorazepam was monitored to determine outcome categories. Results: The clinical and demographic variables of the study sample were analyzed with initial response to IV lorazepam as quick responder (grade-i), moderate and poor responders (grade II, III). Sociodemographic variables like marital status (x2 = 1.62, df = 2, NS) and education status (X2 = 4.57, df = 2, NS) did not approach to statistical significance in outcome. However, the outcome of the low income group patients was significantly better ( X2 = 16.84, df = 2, p < 0.001). Out of 14 (26.92%) patients of first manic episode, only 3 patients showed good response to initial lorazepam treatment (Grade I) and 9 and 2 patients assigned outcome category II and III respectively. Patients with history of multiple episodes had shown better response (X2=11.59, df=1, p<0.001, highly significant). Presence of stressful life events was positively correlated with better response to lorazepam treatment (x2==6.73, df=1, p<0.01 significant). Anxious (avoidant) or dependent traits alone or in combination with emotionally unstable personality traits in manic patients significantly determined better episode recovery with lorazepam at one hand proneness for relapses on the other hand Key Words: Bipolar-1 (mania) disorder, Personality traits, outcome, stressful life events. Introduction Multiple studies support an interim consensus that bipolar disorder is a recurrent, lifelong disorder that shows striking individual differences in its severity, duration of symptoms, course, response to treatment and prognosis. However, many features of bipolar disorder remain unclear, which are sources of broad differences in individual outcomes. In the past decade, the focus of attention has shifted to personality dimensions in understanding psychopathology, despite the realization that assessment process are unwieldy, there is now intensive efforts to develop more practical methods to assess personality. Michael Rutter has emphasized Genetic influences, as they apply to individual differences in the liability to show particular behaviors, are strong and pervasive but rarely determinative. Similarly, psychosocial stressors, such as interpersonal trauma, have profound effects of a biological nature by changing the functioning of the brain. 1, 2 Delhi Psychiatry Journal 2008; 11:(1) Delhi Psychiatric Society 73

2 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 APRIL 2008 The classical mania or bipolar I disorder in its current version seems to represent a quantitative exacerbation of normally distributed temperamental traits. In Akiskal s view a temperamental proneness lies in the roots of bipolarity. 3 Observation of a pattern of influence on temperamental dimension exerted by serotonergic and dopaminergic genes suggests that the contribution of these polymorphisms to the clinical presentation of mood disorders could be mediated by an influence on personality differences. 4 The presence of a comorbid personality disorder has been related to increased suicide risk, more frequency of residual symptoms, gr eater fr equency of mixed and depressive features, worse therapeutic response and more treatment adherence problems. 5,6,7 One of the most vexing questions has been the implications of personality features and disorders for treatment outcome in mood disorders. This question has been studied frequently in major depressive disorder but remains almost unstudied in bipolar disorder. 8 Despite the suggestion that personality features are poor prognostic indicators in general depression, less research has addressed these questions in bipolar disorder. Conceptual models linking personality and bipolar disorder are relatively underdeveloped compared with models for major depressive disorder. 9 In this background, we planned a study to understand and probably explain the extreme variability in treatment outcome of manic episodes of bipolar disorders in relation to the personality profile. Material and Methods 52 patients of bipolar (mania) disorder, out of total 430 admitted patients in psychiatry ward, at PBM Hospital, SP Medical College Bikaner, from January 10, to July 9, 2005 were included in the study. The patients with organic diseases or on any drugs for last two weeks were excluded from the study. Immediately after admission all the patients were diagnose as per ICD-10 diagnostic criteria (WHO 1992). 10 Patients of bipolar mania were administered Young Mania Rating Scale (YMRS) to assess the severity of mania. 11 Sociodemographic details were noted on Self Designed Performa. The personality traits and disorders were assessed by the help of ICD-10 module of International Personality Disorder Examination (IPDE). 12 The stress in preceding one month was evaluated by using 41 items Presumptive Stressful Life Event Scale. 13 Diagnostic interviews were performed before pharmacological interventions, at the index hospitalization. Manic symptoms were rated within 6 hours of the admission before any therapeutic interventions and thereafter by every alternate day. Outcome measures Out come and recovery: Episode recovery was defined as no longer meet criteria for an ongoing ICD-10, manic episode. Episode recovery was classified according to response to lorazepam treatment (IV and oral) during first 36 hours and followed by antimanic or antipsychotic, as one of the three categories: Good responder (Grade I): more than 75% manic score reduction on YMRS. Moderate responder (Grade II): 25-74% manic score reduction Minimal responder (Grade III): < 25% manic score reduction. Symptomatic recovery was defined as minimal to no manic symptoms, operationalized as young mania rating score 5 or less. Medication and Treatment compliance After initial socio-demographic, symptomatic and diagnostic assessment, the patients were challenged with IV injections of lorazepam (2 mg) once, twice or maximum thrice depending on clinical response for first 36 hrs. The assessment was repeated on alternative day till discharge. Those patients, who had shown good response clinically and on rating scales (grade I), were treated with only oral lorazepam 6 mg/day and discharged after symptomatic recovery (YMRS score < 5) on the same doses and gradually tapered off within two months follow up. Those patients who had shown moderate (grade II) response during 36 hours of admission were started mood stabilizer (sodiumvalproate) along with lorazepam and discharged on the same, after symptomatic recovery. The patients, who had shown minimal or no (Grade III) response, were switched on combination of mood stabilizer (Sodiumvalproate mg/day) and 74 Delhi Psychiatry Journal 2008; 11:(1) Delhi Psychiatric Society

3 APRIL 2008 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 antipsychotic (Olanzapine 5-30 mg/day). The dose was adjusted as per severity of the symptoms. Subjects, whose manic scores were not reduced up to 50% on YMRS even after 2 weeks, were administered ECTs. These patients were discharged on combination of mood stabilizer and antipsychotics, after symptomatic recovery. Systematic re-evaluations were scheduled at every fortnightly follow up after discharge from hospital, although the actual time patients attended these visit was ± 1.36 days. All the follow up assessment were done by face to face interviews of subject himself as well as their close relatives e.g. parents and siblings by a psychiatrist. Information in follow up interviews included socio demographic changes, symptoms improved or worsened, recent stress, if any, and medication compliance by using the longitudinal interview clinical evaluation [14], YMRS, PSLE and SCID-P. Treatment compliance was defined as full compliance, partial non compliance and total noncompliance. In full compliance, there was evidence from patients and others, that medication regimen were taken in the manner prescribed by the psychiatrist (75-100% adherence to the prescribed regimen). 15 In partial and total non-compliance, the prescribed regimen adherence was 25-75% and 0-25%, respectively. Statistical Analysis Statistical analysis were performed with SPSS for windows software, version 9.0 (SPSS inc. Chicago) and two tailed statistic significance level was set at P < Pearson s correlation coefficients were used to examine the correlation of index manic scores and their improvement after lorazepam treatment. Chi square analysis with Yates s corrections was used to calculate frequency distribution of qualitative data and paired t-test for analyzing effect of lorazepam treatment. Analysis of variance (ANOVA) was used to analyze the effect of lorazepam on manic scores, across all the three outcome categories. Other statistical comparisons were performed as necessary for completeness. Results Characteristics of the study group 52, out of 59 patients who met inclusion/ exclusion criteria and completed follow up of 6 months with full treatment compliance (75-100% adherence to prescribed regimen), were analyzed. 7 (11.86%) patients, who did not complete the study (incomplete follow up and treatment compliance), there were no significant differences between completers and non completers in terms of demographic and clinical variables assessed. 12 patients showed good response to lorazepam,(grade-i) on the basis of initial response to lorazepam 25 and 15 patients were grouped in Grade-II and Grade-III respectively. Analyses of the clinical and demographic variables of the study sample were analyzed across all the three outcome categories. Marital status (x2 = 1.62, df = 2, NS) and education status (X2 = 4.57, df = 2, NS) did not approach to statistical significance in outcome. However, the outcome of the low income group patients was significantly better ( X2 = 16.84, df = 2, p < 0.001). Out of 14 (26.92%) patients of first manic episode, only 3 patients showed good outcome (Grade I) and 9 and 2 patients assigned outcome category II and III respectively. Patients with history of multiple episodes had shown better out come (X2=11.59, df==1, p<0.001, highly significant). Personality dimensions and stress reactivity All 12 patients of grade I outcome category, who showed better episode recovery, had anxious (avoidant) or dependent traits alone or in combination with emotionally unstable impulsive personality traits. Out of these 12, in 10 (83%) patients, manic episode was precipitated by occurrence of anyone of negative stressful life event in preceding one month. 28 (70%) of the grade II and III outcome category patients had no abnormal personality traits but 12 (30%) patients had more malignant personality features e.g. emotionally unstable impulsive or borderline personality disorder or schizoid/paranoid personality traits and only 42% patients precipitated by stress. Presence of stressful life events was positively correlated with lorazepam response (x2==6.73,df=1, p<0.01 significant). Combination of stress with anxious component in personality (n = 10) was associated with good episode recovery (X2 = 22.96, df = 2, p < 0.000). Analysis of relapsed patients All patients were followed for at least 6 months Delhi Psychiatry Journal 2008; 11:(1) Delhi Psychiatric Society 75

4 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 APRIL 2008 after achieving remission or their best clinical state. None of the patient relapsed during follow up of first 3 months. During next 3 months follow up, only 5 patients relapsed (4 patients of grade I and 1 patient of grade II outcome category). There were no significant differences in relapsed patients in terms of their demographic characteristics and medication compliance but out of 5 relapsed patients, 4 (80%) patient s relapse was preceded with stressful life event. As well as they had anxious avoidant or emotionally unstable impulsive personality traits alone or in combination, suggesting that stress precipitates manic episodes in vulnerable persons. Discussion Major affective syndrome (mania), although a common idiopathic psychiatric disorder, to the best of our knowledge, have rarely been studied in systematic follow up to clarify its course and outcome as well as impact of lorazepam treatment and personality profile. This investigation analyzes 52 patients of bipolar disorder presenting with mania and followed up at regular interval for at least 6 months. The outcome was not associated with socio demographic variables in this study is consistent with other earlier studies. 15,16 Observations that most of the patients, who had shown better treatment response (Grade I outcome), had a greater number of previous affective episodes. This group relapsed within the study period with almost similar clinical presentation as index episode. This finding replicates the report of Keller et al that patients with more affective episodes before the index episode, recovered more quickly than patients with fewer prior episode. 17 Our results indicated that the patients with more previous affective episodes (grade I outcome category) were precipitated by occurrence of any recent negative stressful life event and, most of the relapsed patients were also from the same group and preceded with stressful life events. This extends the view that stress is a significant predictor of relapse among the patients with large number of prior affective episodes 18 may be because they had anxious avoidant personality traits and were not on any drugs, even on maintenance doses of lorazepam. In the present investigation, the patients, who responded well to lorazepam treatment, with more previous affective episodes and those whose occurrence of index episode as well as relapse following stressful life event, had a common characteristic that they had premorbid anxious (avoidant) or dependent personality traits in isolation or in combination with emotionally unstable impulsive traits with manic symptoms. Thus, here we can offer a hypothesis that presence of premorbid anxious (avoidant), dependent and impulsive traits not only makes the persons prone to stress and to develop mania but also to get relapsed again and again. The particular mechanisms, by which such personality characteristics might exert vulnerability to develop mania, are required to be focus on psychobiological research. The foregoing findings and considerations suggest the following model: hyperthymic temperament gives rise to pure mania, irritable temperament to mixed mania (which of all mixed states probably best deserves the designation of dysphoric mania ), the depressive temperament gives rise to anxious-depressive (despairing) mania, and the cyclothymic temperament to an unstablelabile mixed state, 19 in support of our hypothesis, National Institute of Mental Health Collaborative Program on the Psychobiology of Depression 20 and some other studies 21,22 have reported that the patients who have high scores on neuroticism extroversion intr oversion, interpersonal dependency and obsessionality are more vulnerable to get the effects of stressors. Other patients who recovered late with adequate dosage of mood stabilizer, antipsychotics and multiple ECTs, had abnormal premorbid personality features, which were very malignant ones i.e. emotionally unstable impulsive or borderline personality disorder and schizoid/ paranoid personality traits. Despite the suggestion that personality features are poor prognostic indicators in general depression, less research has addressed these questions in bipolar disorder. Conceptual models linking personality and bipolar disorder are relatively underdeveloped compared with models for major depr essive disorder. According to Priya Bajaj; Peter Tyrer 2005, the limited findings that are available from small studies are supportive of the notion that personality pathology influences outcome negatively. 9,23,24 76 Delhi Psychiatry Journal 2008; 11:(1) Delhi Psychiatric Society

5 APRIL 2008 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 Personality disorder traits predict poorer medication compliance among bipolar adults 25,26 and the social support that buffers against relapse is lacking. 27 Bipolar patients with personality disorders also spend more days in the hospital in a given year, 28 are less likely to achieve symptomatic recovery, 29 have more severe mood disorder symptoms, and function at a lower level than those without personality disorders. A number of limitations should be considered when interpreting the results of this study. First the sample size is small and hospitalization based sampling may limit generalization by excluding patients with illness not considered sufficiently severe to require hospitalization. Second the exclusion of patients with incomplete follow up and poor treatment compliance may have affected the analysis. Finally the key investigators were not blind to the baseline information, so that the valuation of relapsed patients could have been biased by knowledge of baseline measures. But the accuracy of gathering information, however, is strengthened by the high reliability found between information collected by the key investigators. Despite these limitations, this study can be considered a preliminary but logical and explicit exploration, of the impact of personality traits and disorders on outcome of bipolar patients presented with mania and also how lorazepam treatment, stress reactivity, number of previous episodes and personality factors make a difference. Larger sample, longer duration follow up studies focusing on assessment of personality dimensions are the need of time, as the results of these studies are likely to have implications for clinicians as well as researcher for developing a model of understanding the phenomena. References 1. Rutter M; The interplay of nature, nurture, and developmental influences; the challenged for mental health. Arch Gen Psychiatry 2002; 59 : Glen O.Gabbard: Mind Brain and Personality disorders: Am J Psychiatry, 2005; 162 : Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Keller M, Warshaw M, Clyton P, Goodwin FK. Switching from unipolar to bipolar II: an 11year prospective study of clinical and temperamental predictors in 559 patients. Arch. Gen. Psychiatry 1995; 52 : Alessandro Serretti, Laura Mandelli, Cristina Lorenzi, Samuela Landoni, Raffaella Calati, Chiara Insacco C. Robert Cloninger. Temperament and Character in Mood Disorders: Influence of DRD4, SERTPR, TPH and MAO-A Polymorphisms. Neuropsychobiology 2006; 53 : Bieling PJ, MacQueen GM, Marriot MJ, et al. Longitudinal outcome in patients with bipolar disorder assessed by life-charting is influenced by DSM-IV personality disorder symptoms. Bipolar Disord 2003; 5 : Leverich GS, Altshuler LL, Frye MA, et al. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J Clin Psychiatry 2003; 64 : George EL, Miklowitz DJ, Richards JA, et al. The comorbidity of bipolar disorders: prevalence and clinical correlates. Bipolar Disord 2003; 5 : Shea MT, Widiger TA, Klein MH. Comorbidity of personality disorders and depression: implications for treatment. J Consult Clin Psych 1992; 60 : Bajaj P, Tyrer P. Managing Mood Disorders and Comorbid Personality Disorders, Curr Opin Psychiatry, 2005; 18(1) : World Health Organization. The ICD 10 Classification of Mental and Behavioral Disorders. Clinical Descriptions and Diagnostic Guidelines. WHO, Geneva Young RC, Biggs JT, Ziegler VE. A rating scale for mania: Reliability validity and sensitivity. Br. J Psychiatry, 1978; 133 : World Health Organization. The ICD 10 International Personality Disorder Examination. WHO, Geneva Gurmit Singh PSLE 14. Keller MB, Lavori PW, Friedman B, Nielsen E, Endicott J, McDonald-Scott P, Anderasen NC: The longitudinal Interval Follw up evaluation: A comprehensive method for Delhi Psychiatry Journal 2008; 11:(1) Delhi Psychiatric Society 77

6 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 APRIL 2008 assessing outcome in prospective longitudinal studies. Arch Gen Psychiatry 1987; 44 : MacQueen GM, Young LT, Joffe RT: A review of psychosocial outcome in patients with bipolar disorder. Acta psychiatr. Scand 2001; 13 : Turvey CL, Coryell WH, Solomon DA, Leon AC Endicott J, Keller MB, Akiskal H. Longterm prognosis of bipolar I disorder. Acta Psychiatr. Scand 1998; 99: Martin B. Keller, Philip W. Lavori, William Coryell, Nancy C. Andreasen, Jean Endicott, Paula J. Clayton, Gerald L. Klerman, Robert MA, Hirschfeld. Differential outcome of pure manic, mixed/cycling and pure depression episodes in patients with bipolar illness. JAMA 1986; 255(22) : Joel Swendsen, Constance Hammen, Tracy Heller, Michael Gitlin. Correlates of stress reactivity in patients with bipolar disorder. Am J Psychiatry 1995; 152 : Akiskal HS, Hantouche E, Bourgeois M. Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN). J Affect Disord. 1998; 50 : Hirschfeld RM, Kelerman GL, Clayton PJ, Keller MB: Personality and depression: empirical findings. Arch Gen Psychiatry 1983; 40 : Duggan CF, Lee AS, Murray RM: Does personality predict long term outcome in depressioin? Br J. Psychiatry 1990; 157 : Abou Saleh MT, Coppen A. Who responds to prophylactic lithium? J affect Disord 1986; 10 : Bieling PJ, MacQueen GM, Marriot MJ, et al. Longitudinal outcome in patients with bipolar disorder assessed by life-charting is influenced by DSM-IV personality disorder symptoms. Bipolar Disord 2003; 5 : Susan LM, Lori LA, Trisha S, Paul EK, Mark AF, Kirk DD, Willem AN. Axis I Psychiatric Comorbidity and Its Relationship to Historical Illness Variables in 288 Patients With Bipolar Disorder. Am J Psychiatry 158 : , March Colom F, Vieta E, Martinez-Aran A, et al. Clinical factors associated with treatment noncompliance in euthymic bipolar patients. J Clin Psychiatry 2000; 61 : Schou M. No help from lithium? About patients who might have been but were not helped by prophylactic lithium treatment. Compr Psychiatry 1988; 29 : O Connell RA, Mayo JA, Eng LK, et al. Social support and long-term lithium outcome. Br J Psychiatry 1985; 147 : Barbato N, Hafner RJ. Comorbidity of bipolar and personality disorders. Aust N Z J Psychiatry 1998; 32 : Dunayevich E, Sax KW, Keck PE, et al. Twelve-month outcome in bipolar patients with and without personality disorders. J Clin Psychiatry 2000; 61 : Delhi Psychiatry Journal 2008; 11:(1) Delhi Psychiatric Society