- Email: [email protected]
P.2.e.007 Outcome of bipolar illness and comorbid personality disorder
P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical) (Log Rank: c2 =18.00, p < 0.001; Breslow: c2 =13.93, p < 0.001) or Atypical Antipsychotic monotherapy (Log Rank: c2 =8.61, p = 0.003; Breslow: c2 =8.35, p = 0.004). Valproate association with an Atypical Antipsychotic was superior in terms of relapse prevention to Valproate monotherapy (Log Rank: c2 =8.55, p = 0.003; Breslow: c2 =7.22, p = 0.007), but not to Lithium (Log Rank: c2 =0.35, p = 0.55; Breslow: c2 =2.36, p = 0.12) and Atypical Antipsychotic (Log Rank: c2 =1.25, p = 0.26; Breslow: c2 =2.42, p = 0.12) monotherapies. All treatments were well tolerated by patients and in particular just 4 patients showed extrapyramidal symptoms (EPS) and 2 metabolic alterations. However, the treatment groups were not different in terms of side effects presentation (c2 =7.28, df=10, p = 0.38). Conclusions: These preliminary data seem to confirm results of a previous study from our group [1]. The combination therapy with a Mood Stabilizer and an Atypical Antipsychotic would be more effective in preventing major affective recurrences in bipolar patients. In particular, Lithium association with an Atypical Antipsychotic would be result particularly effective in long termtreatment of BD. References [1] Altamura, A.C., Mundo, E., Dell’Osso, B., Tacchini, G., Buoli M., Calabrese, J.R., 2008. Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar Disorder: a 4-year follow-up naturalistic study. J Affect Disord 110, 135–141. [2] Fountoulakis, K.N., Vieta E., 2008. Treatment of bipolar disorder: a systematic review of available data and clinical perspectives. Int J Neuropsychopharmacol 11, 999–1029. [3] Vieta, E., Suppes, T., Eggens I., Persson, I., Paulsson, B., Brecher, M., 2008. Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). J Affect Disord 109, 251−63.
P.2.e.006 Can we distinguish bipolar from unipolar depression: preliminary results Hranov1 ° ,
Simov2 ,
Hranov3 .
1 University
V. G. Hospital L.G. “St. Naum”, 2nd Psychiatric Clinic, Sofia, Bulgaria; 2 University General Hospital “Aleksandrovska”, Psychiatric Clinic, Sofia, Bulgaria; 3 University Hospital “St. Naum”, 1st Psychiatric Clinic, Sofia, Bulgaria Introduction: Bipolar disorder presents initially with a depressive episode in 35% to 60% of patients making accurate early diagnosis really difficult. There are currently no accepted diagnostic criteria for bipolar depression for either research or clinical purposes. Switch rates among initially depressed patients are as high as nearly 40% in long-term follow-ups [1]. The delay in proper diagnosis can have a grave impact on treatment outcome and on long-term prognosis. Yet, there is an evolving notion that there are clinically relevant differences in patient characteristics, clinical course, diagnostic features, and response to antidepressants between the two mood disorders [2]. The purpose of this study was to search for clinical/historic identifiers of the bipolar nature of a presenting major depressive episode. Methods: 60 consecutive inpatients with at least 3 previous affective episodes: 14 males and 16 females with bipolar (BPD), and as many with unipolar depression (UPD) diagnosed by the MINI were studied. Demographic indices, onset and course of illness parameters, family history, psychosocial development, relevant life events and stressors, etc. were systematically explored. Results: Mean age was 40.8 years for BPD versus 44.8 years for UPD. 46.7% UPD and 16.7% BPD patients were university
S405
graduates (p < 0.01). 63.3% of the UPD group and 50% of the BPD group were married (n.s.), and 16.7% of the BPD patients versus 6.7% of the UPD patients were divorced (n.s.). 40.0% of BPD and 46.6% of UPD patients were unemployed or on social security pension (n.s.). Relatives with BAD I, BAD II, cyclothymic disorder, hyperthymic disorder; eccentrics; artistically gifted persons were found in the families of 86.7% BPD versus those of 16.7% UPD patients (p < 0.001). Mean age at onset was 23.8 years in bipolars versus 29.0 years in unipolars. 5 bipolars and 4 unipolars (n.s.) had committed suicidal attempts prior to study. 83.3% of BPD versus 16.7% of UPD patients experienced evening brightening and invigoration (p < 0.001). Inter-episode symptoms (emotional instability; high anxiety; suicidal thoughts; disturbed appetite, sleep, sexuality and/or disturbed psychomotor performance) were registered during the preceding 2 year-period in 56.6% of BPD versus 30.0% of UPD patients (p < 0.05). Conclusions: Compared to patients with UPD, patients with BPD had much higher familial loading with bipolar spectrum disorders. Early onset of the first affective episode, incomplete remissions, and mood lability during depression provide some potential diagnostic information for distinguishing bipolar from unipolar depression. Suicidality, vocational difficulties, reliance on social support were highly prevalent in both groups, yet not as significantly differing as to be used for distinguishing between the two groups. Bipolar disorder was more deleterious to educational achievement than recurrent unipolar depression. True distinguishing clinical features should be sought in energy level and in behavioural indices [also 2,3]. There were much more marked diurnal variations of activity and energy in BPD. References [1] Akiskal, H.S., Maser, J.D., Zeller, P.J., et al., 1995. Switching from “unipolar” to “bipolar II”: an 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 52, 114–123. [2] Bowden, C.L., 2005. A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord 84, 117–125. [3] Mansell, W., Colom, F., Scott, F., 2005. The nature and treatment of depression in bipolar disorder: a review and implications for future psychological investigation. Clin Psychol Rev 25, 1076–1100.
P.2.e.007 Outcome of bipolar illness and comorbid personality disorder O. Garcia L´opez1 ° , P. Fernandez-Arg¨uelles1 , N. Casas1 , M. Camacho1 , J.M. Garcia1 . 1 Hospital Universitario ‘V. Macarena’, Psiquiatria, Sevilla, Spain Introduction: The purpose of this study was to investigate whether the presence of comorbid personality disorder influences the course of bipolar illness. Subjects with co-occurring bipolar disorder and axis II personality disorders differ from bipolar patients without personality disorders in the clinical correlates [1]. Methods: We examined 40 Bipolar disorder patients (DSMIV criteria) recluted in University Hospital of Seville. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with ‘pure’ bipolar patients (n = 10) with regard to demographic, clinical, course of illness variables, age at onset of the first episode, number and type of affective episodes, duration of bipolar disorder, and number of hospitalizations. There were
S406
P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical)
10 men and 30 women, with a mean age of 46.1 (SD 12.7) years (range 23 to 71 year). Continuous variables were analyzed with the Student’s t test and the relationship between continuous variables with the Pearson product-moment correlation coefficient (r) with the SPSS 11.0. A P of 0.05 or less was considered statistically significant. Results:With comorbid personality disorder (n = 30) included a mean age at the first episode of 27.6 years, mean duration of disease of 19.3 years and a mean number of hospitalizations of 4.8. The mean number of depressive episodes was 5.4, maniac episodes 3.2, and hypomaniac episodes 2.2. When this group was compared with those without comorbid personality disorder (Table1) statistically significant differences regarding features of the bipolar illness were not observed. These data are not in agreement with data reported [2], but group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness and the number of hospitalizations correlated with depressive episodes, and there was an inverse correlation between age at the first episode and duration of bipolar illness. Conclusions: Study not showed significant differences in the clinical course and history of bipolar illness between bipolar patients with and without comorbid personality disorder. Table 1. Depressive
Maniac
Hypomaniac
Bipolar without comorbid personality disorder (n = 10) Depressive r = 0.896∗ r = 0.835∗ Maniac r = 0.896∗ r = 0.946∗ Hypomaniac r = 0.835∗ r = 0.946∗ Age at onset r = 0.652† NS NS Duration disease r = 0.679† r = 0.680† NS Hospitalizations r = 0.815∗ r = 0.967∗ r = 0.969∗ Bipolar with comorbid personality disorder (n = 30) Depressive NS r = 0.392† Maniac NS NS † Hypomaniac r = 0.392 NS Age at onset NS NS NS Duration disease NS NS NS ∗ Hospitalizations r = 0.531 NS NS
Age at onset
Duration disease
Hospitalizations
r = 0.652† NS NS
r = 0.679† r = 0.680† NS NS
r = 0.815∗ r = 0.967∗ r = 0.969∗
NS NS NS NS NS NS NS
NS NS
NS NS NS NS NS
r = 0.531∗ NS NS NS NS
NS
References [1] George EL, Miklowitz DJ, Richards JA, et al. 2003. The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates. Bipolar Disord, 5:115−22. [2] Vieta E, Colom F, Corbella B, et al. 2001. Clinical correlates of psychiatric comorbidity in bipolar I patients. Bipolar Disord, 3:253−8.
P.2.e.008 Initial antidepressant monotherapy in bipolar depression is associated with more depressive relapses and switches M. Valent´ı1 ° , I. Pacchiarotti1 , A.M.A. Nivoli1 , A. Murru1 , F. Colom1 , E. Vieta1 . 1 Institute of Neuroscience. Hospital Cl´ınic, Bipolar Disorders Program, Barcelona, Spain Introduction: The use of antidepressants (AD) in bipolar depression is an object of a long-standing debate about their true effectiveness and safety, in particular on the risk for manic and/or mixed switch, the risk for suicide, and the risk for development of rapid cycling [1]. No antidepressant is specifically licensed for the treatment of bipolar depression. Indeed, there is a discrepancy among regulatory recommendations, data emerging from randomized controlled trials and what occurs in clinical practice. Thus, AD continue to be largely prescribed − in monotherapy or in
combination with mood stabilisers (MS) − for bipolar depression, and they are the most used pharmacological treatment in bipolar disorder after lithium, even in monotherapy [1,2]. Objectives: The purpose of this study was to analyse the clinical characteristics and outcome of a sample of patients with bipolar disorder treated with AD for the first time during a depressive episode. Methods: Among three-hundred one DSM-IV bipolar I and II patients (N = 301), two-hundred twenty-one (N = 221) were enrolled for this study in the Bipolar Disorders Program of Barcelona, which provides integrated care for difficult-to-treat bipolar patients derived from all over Spain. The impact of antidepressants treatment − in monotherapy or in combination with mood stabilisers − on the outcome of bipolar illness was evaluated by comparing a group of bipolar subjects who were treated for the first time with an antidepressant as monotherapy (N = 165) (AM), with a similar representative sample of bipolar patients who were treated with the first AD in combination with MS (N = 56) (AC). The two groups were compared regarding clinical variables. Results: Most bipolar patients (N = 221, 73.4%) had been prescribed antidepressants at certain point during the course of their illness. The first AD was prescribed on average during the second depressive episode (mean: 1.9 SD: 1.8). The majority of subjects (74.6%) started the first AD as monotherapy (AM group, N = 165), while 25.3% (AC group, N = 56) was treated with AD in combination with MS. Age of diagnosis and delay of diagnostic of bipolar disorder were higher for the AM group compared to AC group (p < 0.001, in both comparisons). The main differences between the two groups involved number of depressive relapses, which was significantly higher in the AM group compared to AC group (68.5% vs 44.6%, p = 0.001), and number of switches into mania, which was also higher in the AM group compared to AC group (75.8% vs 46.4%, p < 0.001). Conclusions: Antidepressants are widely prescribed in clinical practice for bipolar depression and they are often used as monotherapy in the early phase of bipolar illness. Antidepressant monotherapy, and probably the lack of a mood stabilizer in combination to the first AD, are associated to an increased risk of relapse of depression and switch into mania. Antidepressant monotherapy should be discouraged as initial treatment for bipolar depression. References [1] Vieta E. Antidepressants in bipolar depression. Acta Psychiatr Scand 2008;118(5):335−6. [2] Baldessarini RJ, Leahy L, Arcona S, Gause D, Zhang W, Hennen J. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv 2007;58(1):85−91.
P.2.e.009 Gender differences in bipolar disorders A.M.A. Nivoli1 ° , F. Colom2 , A. Rosa R2 , D. Popovic2 , I. Pacchiarotti2 , A. Murru2 , E. Vieta2 . 1 University Of Sassari and Bipolar Disorders Program Institute of Neuroscience Hospital Clinic University of Barcelona IDIBAPS CIBERSAM, Departement Of Psychiatry, Barcelona, Spain; 2 Bipolar Disorders Program Institute of Neuroscience Hospital Clinic University of Barcelona IDIBAPS CIBERSAM Barcelona Spain., Departement Of Psychiatry, Barcelona, Spain Introduction: Gender differences amongst bipolar patients regarding epidemiological and clinical variables are relatively well
P.2.e.006 Can we distinguish bipolar from unipolar depression: preliminary results Hranov1 ° ,
Simov2 ,
Hranov3 .
1 University
V. G. Hospital L.G. “St. Naum”, 2nd Psychiatric Clinic, Sofia, Bulgaria; 2 University General Hospital “Aleksandrovska”, Psychiatric Clinic, Sofia, Bulgaria; 3 University Hospital “St. Naum”, 1st Psychiatric Clinic, Sofia, Bulgaria Introduction: Bipolar disorder presents initially with a depressive episode in 35% to 60% of patients making accurate early diagnosis really difficult. There are currently no accepted diagnostic criteria for bipolar depression for either research or clinical purposes. Switch rates among initially depressed patients are as high as nearly 40% in long-term follow-ups [1]. The delay in proper diagnosis can have a grave impact on treatment outcome and on long-term prognosis. Yet, there is an evolving notion that there are clinically relevant differences in patient characteristics, clinical course, diagnostic features, and response to antidepressants between the two mood disorders [2]. The purpose of this study was to search for clinical/historic identifiers of the bipolar nature of a presenting major depressive episode. Methods: 60 consecutive inpatients with at least 3 previous affective episodes: 14 males and 16 females with bipolar (BPD), and as many with unipolar depression (UPD) diagnosed by the MINI were studied. Demographic indices, onset and course of illness parameters, family history, psychosocial development, relevant life events and stressors, etc. were systematically explored. Results: Mean age was 40.8 years for BPD versus 44.8 years for UPD. 46.7% UPD and 16.7% BPD patients were university
S405
graduates (p < 0.01). 63.3% of the UPD group and 50% of the BPD group were married (n.s.), and 16.7% of the BPD patients versus 6.7% of the UPD patients were divorced (n.s.). 40.0% of BPD and 46.6% of UPD patients were unemployed or on social security pension (n.s.). Relatives with BAD I, BAD II, cyclothymic disorder, hyperthymic disorder; eccentrics; artistically gifted persons were found in the families of 86.7% BPD versus those of 16.7% UPD patients (p < 0.001). Mean age at onset was 23.8 years in bipolars versus 29.0 years in unipolars. 5 bipolars and 4 unipolars (n.s.) had committed suicidal attempts prior to study. 83.3% of BPD versus 16.7% of UPD patients experienced evening brightening and invigoration (p < 0.001). Inter-episode symptoms (emotional instability; high anxiety; suicidal thoughts; disturbed appetite, sleep, sexuality and/or disturbed psychomotor performance) were registered during the preceding 2 year-period in 56.6% of BPD versus 30.0% of UPD patients (p < 0.05). Conclusions: Compared to patients with UPD, patients with BPD had much higher familial loading with bipolar spectrum disorders. Early onset of the first affective episode, incomplete remissions, and mood lability during depression provide some potential diagnostic information for distinguishing bipolar from unipolar depression. Suicidality, vocational difficulties, reliance on social support were highly prevalent in both groups, yet not as significantly differing as to be used for distinguishing between the two groups. Bipolar disorder was more deleterious to educational achievement than recurrent unipolar depression. True distinguishing clinical features should be sought in energy level and in behavioural indices [also 2,3]. There were much more marked diurnal variations of activity and energy in BPD. References [1] Akiskal, H.S., Maser, J.D., Zeller, P.J., et al., 1995. Switching from “unipolar” to “bipolar II”: an 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 52, 114–123. [2] Bowden, C.L., 2005. A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord 84, 117–125. [3] Mansell, W., Colom, F., Scott, F., 2005. The nature and treatment of depression in bipolar disorder: a review and implications for future psychological investigation. Clin Psychol Rev 25, 1076–1100.
P.2.e.007 Outcome of bipolar illness and comorbid personality disorder O. Garcia L´opez1 ° , P. Fernandez-Arg¨uelles1 , N. Casas1 , M. Camacho1 , J.M. Garcia1 . 1 Hospital Universitario ‘V. Macarena’, Psiquiatria, Sevilla, Spain Introduction: The purpose of this study was to investigate whether the presence of comorbid personality disorder influences the course of bipolar illness. Subjects with co-occurring bipolar disorder and axis II personality disorders differ from bipolar patients without personality disorders in the clinical correlates [1]. Methods: We examined 40 Bipolar disorder patients (DSMIV criteria) recluted in University Hospital of Seville. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with ‘pure’ bipolar patients (n = 10) with regard to demographic, clinical, course of illness variables, age at onset of the first episode, number and type of affective episodes, duration of bipolar disorder, and number of hospitalizations. There were
S406
P.2.e. Affective disorders and antidepressants − Bipolar disorders (clinical)
10 men and 30 women, with a mean age of 46.1 (SD 12.7) years (range 23 to 71 year). Continuous variables were analyzed with the Student’s t test and the relationship between continuous variables with the Pearson product-moment correlation coefficient (r) with the SPSS 11.0. A P of 0.05 or less was considered statistically significant. Results:With comorbid personality disorder (n = 30) included a mean age at the first episode of 27.6 years, mean duration of disease of 19.3 years and a mean number of hospitalizations of 4.8. The mean number of depressive episodes was 5.4, maniac episodes 3.2, and hypomaniac episodes 2.2. When this group was compared with those without comorbid personality disorder (Table1) statistically significant differences regarding features of the bipolar illness were not observed. These data are not in agreement with data reported [2], but group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness and the number of hospitalizations correlated with depressive episodes, and there was an inverse correlation between age at the first episode and duration of bipolar illness. Conclusions: Study not showed significant differences in the clinical course and history of bipolar illness between bipolar patients with and without comorbid personality disorder. Table 1. Depressive
Maniac
Hypomaniac
Bipolar without comorbid personality disorder (n = 10) Depressive r = 0.896∗ r = 0.835∗ Maniac r = 0.896∗ r = 0.946∗ Hypomaniac r = 0.835∗ r = 0.946∗ Age at onset r = 0.652† NS NS Duration disease r = 0.679† r = 0.680† NS Hospitalizations r = 0.815∗ r = 0.967∗ r = 0.969∗ Bipolar with comorbid personality disorder (n = 30) Depressive NS r = 0.392† Maniac NS NS † Hypomaniac r = 0.392 NS Age at onset NS NS NS Duration disease NS NS NS ∗ Hospitalizations r = 0.531 NS NS
Age at onset
Duration disease
Hospitalizations
r = 0.652† NS NS
r = 0.679† r = 0.680† NS NS
r = 0.815∗ r = 0.967∗ r = 0.969∗
NS NS NS NS NS NS NS
NS NS
NS NS NS NS NS
r = 0.531∗ NS NS NS NS
NS
References [1] George EL, Miklowitz DJ, Richards JA, et al. 2003. The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates. Bipolar Disord, 5:115−22. [2] Vieta E, Colom F, Corbella B, et al. 2001. Clinical correlates of psychiatric comorbidity in bipolar I patients. Bipolar Disord, 3:253−8.
P.2.e.008 Initial antidepressant monotherapy in bipolar depression is associated with more depressive relapses and switches M. Valent´ı1 ° , I. Pacchiarotti1 , A.M.A. Nivoli1 , A. Murru1 , F. Colom1 , E. Vieta1 . 1 Institute of Neuroscience. Hospital Cl´ınic, Bipolar Disorders Program, Barcelona, Spain Introduction: The use of antidepressants (AD) in bipolar depression is an object of a long-standing debate about their true effectiveness and safety, in particular on the risk for manic and/or mixed switch, the risk for suicide, and the risk for development of rapid cycling [1]. No antidepressant is specifically licensed for the treatment of bipolar depression. Indeed, there is a discrepancy among regulatory recommendations, data emerging from randomized controlled trials and what occurs in clinical practice. Thus, AD continue to be largely prescribed − in monotherapy or in
combination with mood stabilisers (MS) − for bipolar depression, and they are the most used pharmacological treatment in bipolar disorder after lithium, even in monotherapy [1,2]. Objectives: The purpose of this study was to analyse the clinical characteristics and outcome of a sample of patients with bipolar disorder treated with AD for the first time during a depressive episode. Methods: Among three-hundred one DSM-IV bipolar I and II patients (N = 301), two-hundred twenty-one (N = 221) were enrolled for this study in the Bipolar Disorders Program of Barcelona, which provides integrated care for difficult-to-treat bipolar patients derived from all over Spain. The impact of antidepressants treatment − in monotherapy or in combination with mood stabilisers − on the outcome of bipolar illness was evaluated by comparing a group of bipolar subjects who were treated for the first time with an antidepressant as monotherapy (N = 165) (AM), with a similar representative sample of bipolar patients who were treated with the first AD in combination with MS (N = 56) (AC). The two groups were compared regarding clinical variables. Results: Most bipolar patients (N = 221, 73.4%) had been prescribed antidepressants at certain point during the course of their illness. The first AD was prescribed on average during the second depressive episode (mean: 1.9 SD: 1.8). The majority of subjects (74.6%) started the first AD as monotherapy (AM group, N = 165), while 25.3% (AC group, N = 56) was treated with AD in combination with MS. Age of diagnosis and delay of diagnostic of bipolar disorder were higher for the AM group compared to AC group (p < 0.001, in both comparisons). The main differences between the two groups involved number of depressive relapses, which was significantly higher in the AM group compared to AC group (68.5% vs 44.6%, p = 0.001), and number of switches into mania, which was also higher in the AM group compared to AC group (75.8% vs 46.4%, p < 0.001). Conclusions: Antidepressants are widely prescribed in clinical practice for bipolar depression and they are often used as monotherapy in the early phase of bipolar illness. Antidepressant monotherapy, and probably the lack of a mood stabilizer in combination to the first AD, are associated to an increased risk of relapse of depression and switch into mania. Antidepressant monotherapy should be discouraged as initial treatment for bipolar depression. References [1] Vieta E. Antidepressants in bipolar depression. Acta Psychiatr Scand 2008;118(5):335−6. [2] Baldessarini RJ, Leahy L, Arcona S, Gause D, Zhang W, Hennen J. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv 2007;58(1):85−91.
P.2.e.009 Gender differences in bipolar disorders A.M.A. Nivoli1 ° , F. Colom2 , A. Rosa R2 , D. Popovic2 , I. Pacchiarotti2 , A. Murru2 , E. Vieta2 . 1 University Of Sassari and Bipolar Disorders Program Institute of Neuroscience Hospital Clinic University of Barcelona IDIBAPS CIBERSAM, Departement Of Psychiatry, Barcelona, Spain; 2 Bipolar Disorders Program Institute of Neuroscience Hospital Clinic University of Barcelona IDIBAPS CIBERSAM Barcelona Spain., Departement Of Psychiatry, Barcelona, Spain Introduction: Gender differences amongst bipolar patients regarding epidemiological and clinical variables are relatively well